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

Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice.

PubMed

Stein, Elisabeth A; Pinkert, Sandra; Becher, Peter Moritz; Geisler, Anja; Zeichhardt, Heinz; Klopfleisch, Robert; Poller, Wolfgang; Tschöpe, Carsten; Lassner, Dirk; Fechner, Henry; Kurreck, Jens

2015-02-15

Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated. A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function. Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nebivolol/valsartan: Fixed-dose combination for treatment of hypertension.

PubMed

Paton, D M

2017-01-01

Clinical trials demonstrated that a fixed-dose combination (FDC) of the beta-blocker nebivolol (5 mg) and the angiotensin II antagonist valsartan (80 mg) produced a significant reduction of both diastolic and systolic blood pressure in patients with hypertension. Both nebivolol and valsartan contributed to this effect, partial additivity of 86.6% and 82.2% being observed for diastolic and systolic blood pressure, respectively. These values are very similar to the additivity ratios of other recently approved FDCs for hypertension. Use of the FDC nebivolol 5 mg/valsartan 80 mg formulation was associated with a low incidence of treatment-related adverse effects and of serious adverse effects. There was no evidence of adverse effects due to beta2-adrenoceptor blockade. The FDC (Byvalson) was approved and launched in 2016 in the U.S. for the treatment of hypertension. Copyright 2017 Clarivate Analytics.

Improvement of bioinsecticides production through adaptation of Bacillus thuringiensis cells to heat treatment and NaCl addition.

PubMed

Ghribi, D; Zouari, N; Jaoua, S

2005-01-01

The present work aimed to increase yields of delta-endotoxin production through adaptation of Bacillus thuringiensis cells to heat shock and sodium chloride and to investigate their involvements in bioinsecticides production improvement. Growing B. thuringiensis cells were heat treated after different incubation times to study the response of the adaptative surviving cells in terms of delta-endotoxin synthesis. Similarly, adaptation of B. thuringiensis cells to sodium chloride was investigated. Adaptation to combined stressors was also evaluated. When applied separately in the glucose-based medium, 20-min heat treatment of 6-h-old cultures and addition of 7 g l(-1) NaCl at the beginning of the incubation gave respectively 38 and 27% delta-endotoxin production improvements. Heat shock improved toxin synthesis yields, while NaCl addition improved delta-endotoxin production by increasing the spore titres without significant effect on toxin synthesis yields. Cumulative improvements (66%) were obtained by combination of the two stressors at the conditions previously established for each one. Interestingly, when the similar approach was conducted by using the large scale production medium based on gruel and fish meal, 17, 8 and 29% delta-endotoxin production improvements were respectively, obtained with heat shock, NaCl and combined stressors. Heat treatment of vegetative B. thuringiensis cells and NaCl addition to the culture media improved bioinsecticides production. Heat treatment increased toxin synthesis yields, while addition of NaCl increased biomass production yields. Cumulative improvements of 66 and 29% were obtained in glucose and economic production media, respectively. Overproduction of bioinsecticides by B. thuringiensis could be obtained by the combination of heat treatment of vegetative cells and addition of NaCl to the culture medium. This should contribute to a significant reduction of the cost of B. thuringiensis bioinsecticides production and

Producing Hybrid Metal Composites by Combining Additive Manufacturing and Casting

DOE PAGES

Pawlowski, Alex E.; Splitter, Derek A.; Muth, Thomas R.; ...

2017-10-01

Additive manufacturing by itself provides many benefits, but by combining different materials processing techniques like traditional casting with additive manufacturing to create hybrid processes, custom materials can be tailor-made and mass produced for applications with specific performance needs.

Structure and microhardness of the plasma sprayed composite coatings after combined treatment

NASA Astrophysics Data System (ADS)

Ivannikov, A. Yu; Kalita, V. I.; Komlev, D. I.; Radyuk, A. A.; Bagmutov, V. P.; Zakharov, I. N.; Parshev, S. N.; Denisevich, D. S.

2018-04-01

The principal aim of this study was to evaluate the effect of combination of electromechanical treatment (EMT) and ultrasonic treatment on structure and microhardness of air plasma sprayed composite coatings from Ni–20Cr alloy and R6M5 high speed steel (HSS). The results of the microstructural studies showed fundamental changes of the treated by the EMT plasma sprayed coating with the formation of nanostructured crystalline phases. As a consequence of the coating thus formed, the number of pores in the coating structure reduced from 10.0±1.5% to 2.0±0.5%, the surface microhardness increased from 3100±500 MPa to 7900±400 MPa. Additional ultrasonic treatment on the selected mode decreased surface waviness, which was formed on the surface of the plasma sprayed composite coatings after the EMT. The obtained results revealed the high potential of the combined treatment for post-treatment of the plasma sprayed coatings.

Object attributes combine additively in visual search

PubMed Central

Pramod, R. T.; Arun, S. P.

2016-01-01

We perceive objects as containing a variety of attributes: local features, relations between features, internal details, and global properties. But we know little about how they combine. Here, we report a remarkably simple additive rule that governs how these diverse object attributes combine in vision. The perceived dissimilarity between two objects was accurately explained as a sum of (a) spatially tuned local contour-matching processes modulated by part decomposition; (b) differences in internal details, such as texture; (c) differences in emergent attributes, such as symmetry; and (d) differences in global properties, such as orientation or overall configuration of parts. Our results elucidate an enduring question in object vision by showing that the whole object is not a sum of its parts but a sum of its many attributes. PMID:26967014

Object attributes combine additively in visual search.

PubMed

Pramod, R T; Arun, S P

2016-01-01

We perceive objects as containing a variety of attributes: local features, relations between features, internal details, and global properties. But we know little about how they combine. Here, we report a remarkably simple additive rule that governs how these diverse object attributes combine in vision. The perceived dissimilarity between two objects was accurately explained as a sum of (a) spatially tuned local contour-matching processes modulated by part decomposition; (b) differences in internal details, such as texture; (c) differences in emergent attributes, such as symmetry; and (d) differences in global properties, such as orientation or overall configuration of parts. Our results elucidate an enduring question in object vision by showing that the whole object is not a sum of its parts but a sum of its many attributes.

Protocol for a prospective observational study of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy.

PubMed

Yoo, Jeong-Eun; Yun, Young-Ju; Shin, Yong-Beom; Kim, Nam-Kwen; Kim, Soo-Yeon; Shin, Myung-Jun; Yu, Sun-Ae

2016-06-08

Cerebral palsy leads to many complications as well as delayed motor development, and early intensive rehabilitation in infancy, which is based on the theory of brain plasticity, is emphasized. In addition to conventional treatment, including physical, occupational, or speech-language therapies, children also have a demand for traditional Korean medicine interventions such as acupuncture or herbal medicine; however, a lack of evidence has made traditional Korean medicine difficult to implement in practice. We planned a multicentre, prospective, observational study to assess the effectiveness, safety and cost-effectiveness of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. Three hundred children with cerebral palsy aged 6 to 78 months will be recruited from six institutions. Data from each child are collected every month for a one-year period, during which time treatment might be changed or discontinued. A qualified investigator visits the sites to measure effectiveness variables, including Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory. Adverse events and cost-effectiveness variables are collected using surveys conducted at baseline, mid-study, and end of study, as well as monthly tracking surveys. In the analyses, participants will be classified into two groups: group A children will be the conventional treatment group with physical, occupational, speech-language or other conventional rehabilitation therapies, whereas group B children will be the combination treatment group with traditional Korean medicine interventions, that is, herbal medicine, chuna, moxibustion and acupuncture, in addition to conventional treatment. Only a few clinical case reports have evaluated the effectiveness and safety of traditional Korean medicine; therefore, more data are required to provide optimal information to children with cerebral palsy and their guardians. We hypothesized that

Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

PubMed Central

Garcia, Hector H; Lescano, Andres G; Lanchote, Vera L; Pretell, E Javier; Gonzales, Isidro; Bustos, Javier A; Takayanagui, Osvaldo M; Bonato, Pierina S; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H

2011-01-01

AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. PMID:21332573

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model.

PubMed

Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Zhang, Chi; Cai, Lu

2015-07-01

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. Copyright © 2015 the American Physiological Society.

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

PubMed Central

Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Cai, Lu

2015-01-01

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. PMID:25968574

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

No additional cholesterol-lowering effect observed in the combined treatment of red yeast rice and Lactobacillus casei in hyperlipidemic patients: A double-blind randomized controlled clinical trial.

PubMed

Lee, Chien-Ying; Yu, Min-Chien; Perng, Wu-Tsun; Lin, Chun-Che; Lee, Ming-Yung; Chang, Ya-Lan; Lai, Ya-Yun; Lee, Yi-Ching; Kuan, Yu-Hsiang; Wei, James Cheng-Chung; Shih, Hung-Che

2017-08-01

To observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies. A double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8. At week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride. The combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.

Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

PubMed Central

Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

2011-01-01

Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209

Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

PubMed

Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

2013-01-01

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

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.

Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine.

PubMed

Escobar-Morreale, Héctor F; Botella-Carretero, José I; Morreale de Escobar, Gabriella

2015-01-01

At present, the drug of choice for the treatment of hypothyroidism is levothyroxine sodium, even though the thyroid gland secretes both thyroxine and 3',3,5-triiodothyronine; the latter is the more active of the two at the cellular level because of its higher affinity for the nuclear thyroid hormone receptors. To date, combined levothyroxine plus liothyronine treatment for hypothyroidism has been evaluated in 15 clinical trials in humans. In two studies, combined therapy seemed to have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone; in some of these studies, the patients preferred levothyroxine plus liothyronine combinations. This preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine. Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism. Copyright © 2014 Elsevier Ltd. All rights reserved.

[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.

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.

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

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

Sanitising black water by auto-thermal aerobic digestion (ATAD) combined with ammonia treatment.

PubMed

Nordin, Annika C; Vinnerås, Björn

2015-01-01

The effect of a two-step process on the concentration of pathogens and indicator microorganisms in black water (0.9-1% total solids) was studied. The treatment combined auto-thermal aerobic digestion (ATAD) and ammonia sanitisation. First, the temperature of the black water was increased through ATAD and when a targeted temperature was reached (33, 41 and 45.5 °C studied), urea was added to a 0.5% concentration (total ammonia nitrogen >2.9 g L⁻¹). Escherichia coli and Salmonella spp. were reduced to non-detectable levels within 3 days following urea addition at temperatures above 40 °C, whereas when urea was added at 33 °C E. coli was still present after 8 days. By adding urea at temperatures of 40 °C and above, a 5 log10 reduction in Enterococcus spp. and a 3 log10 reduction in Ascaris suum eggs was achieved 1 week after the addition. With combined ATAD and ammonia treatment using 0.5% ww urea added at an aerobic digestion temperature >40 °C, black water was sanitised regarding the pathogens studied in 2 weeks of total treatment time.

Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.

PubMed

Lutz, Werner K; Vamvakas, Spyros; Kopp-Schneider, Annette; Schlatter, Josef; Stopper, Helga

2002-12-01

Sublinear dose-response relationships are often seen in toxicity testing, particularly with bioassays for carcinogenicity. This is the result of a superimposition of various effects that modulate and contribute to the process of cancer formation. Examples are saturation of detoxification pathways or DNA repair with increasing dose, or regenerative hyperplasia and indirect DNA damage as a consequence of high-dose cytotoxicity and cell death. The response to a combination treatment can appear to be supra-additive, although it is in fact dose-additive along a sublinear dose-response curve for the single agents. Because environmental exposure of humans is usually in a low-dose range and deviation from linearity is less likely at the low-dose end, combination effects should be tested at the lowest observable effect levels (LOEL) of the components. This principle has been applied to combinations of genotoxic agents in various cellular models. For statistical analysis, all experiments were analyzed for deviation from additivity with an n-factor analysis of variance with an interaction term, n being the number of components tested in combination. Benzo[a]pyrene, benz[a]anthracene, and dibenz[a,c]anthracene were tested at the LOEL, separately and in combination, for the induction of revertants in the Ames test, using Salmonella typhimurium TA100 and rat liver S9 fraction. Combined treatment produced no deviation from additivity. The induction of micronuclei in vitro was investigated with ionizing radiation from a 137Cs source and ethyl methanesulfonate. Mouse lymphoma L5178Y cells revealed a significant 40% supra-additive combination effect in an experiment based on three independent replicates for controls and single and combination treatments. On the other hand, two human lymphoblastoid cell lines (TK6 and WTK1) as well as a pilot study with human primary fibroblasts from fetal lung did not show deviation from additivity. Data derived from one cell line should therefore

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.

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

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

PubMed

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

2016-06-01

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

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.

Waste treatment by bacterial additions

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

Deutsch, D.J.; Stigall, E.; Barth, E.

1979-04-23

Companies such as General Environmental Science Corp. and Polybac Corp., which market specialized bacterial cultures for treating industrial wastes, claim that the cultures improve the operation of activated-sludge, trickling-filter, and lagoon-treatment plants, and provide faster system response to startups, variable and shock loads, and cold weather. The effectiveness of the special cultures is difficult to verify and has been questioned by environmental experts, including R. L. Raymond (Suntech Inc.) and E. Barth (EPA), although E. Stigall (EPA) believes they may aid plant recovery after upsets. A study by Business Communications Co. has predicted that the market for such additives willmore » reach $50 million by 1987, from $5 million in 1979. The use of such cultures in Exxon Corp.'s 1 million gal/day activated sludge system at the Benicia, Calif., oil refinery improved the system's performance by 32Vertical Bar3<, resulted in faster unit startups and more stable operation, and reduced foaming. J. T. Baker Co. has used successfully two broad-spectrum dried additives for ammonia removal and hydrocarbon degradation at its 3 million gal/day secondary treatment plant at Phillipsburg, N.J.« less

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

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

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

[Efficacy of HRV-biofeedback as additional treatment of depression and PTSD].

PubMed

Blase, K L; van Dijke, A; Cluitmans, P J M; Vermetten, E

2016-01-01

Heartrate variability biofeedback (HRVB) is a non-invasive treatment in which patients are assumed to self-regulate a physiological dysregulated vagal nerve. Although the therapeutic approach of HRVB is promising in various stress-related disorders, it has only been offered on a regular basis in a few mental health treatment settings. To analyse the efficacy of HRV biofeedback as an additional psychophysiological treatment for depression and PTSD. Systematic review with search terms HRV, biofeedback, PTSD, depression, panic disorder and anxiety disorder. Our search of the literature yielded 789 studies. After critical appraisal using the GRADE method, we selected 6 randomised controlled trials (RCTs) and 4 relevant studies. The RCTs with control groups 'treatment as usual' and muscle relaxation training revealed significant clinical efficacy and better results than control conditions after 4 to 8 weeks training. Although this systematic review shows the popularity of HRV in literature, it does not indicate that HRVB really has been reviewed systematically. Significant outcomes of this limited number of randomised studies indicate there may be a clinical improvement when HRVB training is integrated into treatment of PTSD and depression, particularly when this integration procedure is combined with psychotherapy. More research needs to be done with larger groups and further efforts are needed to integrate HRVB into treatment of stress-related disorders in psychiatry. Future research also needs to focus on the psychophysiological mechanisms involved.

Preferences among four combination nicotine treatments.

PubMed

Schneider, Nina G; Koury, Margaret A; Cortner, Chris; Olmstead, Richard E; Hartman, Neil; Kleinman, Leonard; Kim, Andrew; Chaya, Craig; Leaf, David

2006-09-01

Acute nicotine replacement treatments (NRTs) are disliked or misused, leading to insufficient nicotine intake and poor outcome. Patches provide steady nicotine but are slow and passive. Combining systems may improve efficacy with acute NRTs tailored for compliance. To test initial reactions to and use preferences among combinations of NRTs. Smokers (n=27) tested four combination NRTs in a 5-day crossover trial: 2/4-mg gum + 15-mg patch (G/P), 2/4-mg lozenges + 15-mg patch (L/P), inhaler + 15-mg patch (I/P), and 10 mg + 15-mg patches (P/P). Subjects rated an NRT combination each day after 5-6 h of use and ranked among the NRTs after testing all treatments. Double-patches (P/P) were ranked highest for "ease of use", "safety", and "use in public". However, for "help to quit", 70% preferred some form of acute-patch combination (A/P) compared to 30% choosing P/P. For "use under stress" (an immediate need), 93% preferred A/P systems compared to 7% choosing P/P. L/P ranked lowest for "ease of use", I/P and L/P were lowest on "safety", and I/P ranked lowest for "use in public". Expectations of NRTs changed with test experience for patches (better) and lozenges (worse). In brief testing, all combinations were acceptable. P/P was favored for ease, safety, and public use, but a majority chose A/P systems for help in quitting and use under stress. Combined use is viable and needs to be made known and accessible to smokers.

Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

PubMed Central

Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B

2012-01-01

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with

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

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

39 CFR 3050.41 - Treatment of additional financial reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Treatment of additional financial reports. 3050.41... Treatment of additional financial reports. (a) For purposes of the reports required by § 3050.40(a)(2), the... § 3050.40(c) is fairly stated in all material respects, either in relation to the basic financial...

Removal of Listeria monocytogenes dual-species biofilms using combined enzyme-benzalkonium chloride treatments.

PubMed

Rodríguez-López, Pedro; Carballo-Justo, Alba; Draper, Lorraine A; Cabo, Marta L

2017-01-01

The effects of pronase (PRN), cellulase (CEL) or DNaseI alone or combined with benzalkonium chloride (BAC) against Listeria monocytogenes-carrying biofilms were assayed. The best removal activity against L. monocytogenes-Escherichia coli biofilms was obtained using DNaseI followed by PRN and CEL. Subsequently, a modified logistic model was used to quantify the combined effects of PRN or DNaseI with BAC. A better BAC performance after PRN compared to DNaseI eradicating L. monocytogenes was observed. In E. coli the effects were the opposite. Finally, effects of DNaseI and DNaseI-BAC treatments were compared against two different L. monocytogenes-carrying biofilms. DNaseI-BAC was more effective against L. monocytogenes when co-cultured with E. coli. Nonetheless, comparing the removal effects after BAC addition, these were higher in mixed-biofilms with Pseudomonas fluorescens. However, a high number of released viable cells was observed after combined treatments. These results open new perspectives of enzymes as an anti-biofilm strategy for environmental pathogen control.

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.

Addition of alkali to the hydrothermal-mechanochemical treatment of Eucalyptus enhances its enzymatic saccharification.

PubMed

Ishiguro, Maki; Endo, Takashi

2014-02-01

The effects of alkali on hydrothermal-mechanochemical treatment (hydrothermal treatment combined with wet-milling) were examined with the aim of improving pretreatment of lignocellulosic biomass before enzymatic saccharification. After enzymatic saccharification, the highest glucose yield was obtained by autoclaving at 170°C in the presence of 20% NaOH per substrate weight. The wood fiber was unraveled into finer nanofibers by hydrothermal-mechanochemical treatment, thus increasing the specific surface area of the substrate from 11 to 132m(2)/g. Adding 20% NaOH to the treatment further increased the specific surface area of the already fibrillated substrate by 76% (232m(2)/g) due to lignin removal and ester bond cleavage between lignin and hemicellulose. This increase in specific surface area was closely related to the increase in enzymatic digestibility; therefore, NaOH addition may have enhanced the effect of hydrothermal-mechanochemical treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Combined proportional and additive residual error models in population pharmacokinetic modelling.

PubMed

Proost, Johannes H

2017-11-15

In pharmacokinetic modelling, a combined proportional and additive residual error model is often preferred over a proportional or additive residual error model. Different approaches have been proposed, but a comparison between approaches is still lacking. The theoretical background of the methods is described. Method VAR assumes that the variance of the residual error is the sum of the statistically independent proportional and additive components; this method can be coded in three ways. Method SD assumes that the standard deviation of the residual error is the sum of the proportional and additive components. Using datasets from literature and simulations based on these datasets, the methods are compared using NONMEM. The different coding of methods VAR yield identical results. Using method SD, the values of the parameters describing residual error are lower than for method VAR, but the values of the structural parameters and their inter-individual variability are hardly affected by the choice of the method. Both methods are valid approaches in combined proportional and additive residual error modelling, and selection may be based on OFV. When the result of an analysis is used for simulation purposes, it is essential that the simulation tool uses the same method as used during analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Winery wastewater treatment by combination of Cryptococcus laurentii and Fenton's reagent.

PubMed

Santos, Cátia; Lucas, Marco S; Dias, Albino A; Bezerra, Rui M F; Peres, José A; Sampaio, Ana

2014-12-01

Winery wastewaters (WW) have high levels of organic matter, resulting in high COD and BOD and suspended solids. This paper studies the combination of biological and chemical processes in WW treatment. Among 10 yeast isolates, Filobasidium sp. (AGG 577) and Cryptococcus laurentii (AGG 726) were selected due to their superior performance in COD removal. During WW degradation, COD and total polyphenols (TPP) content removal of 89-90% for Filobasidium sp. and 90-93% for C. laurentii were obtained. However, despite similar degradation efficiency for both yeasts, COD kinetics and pH evolution during treatment reveals that C. laurentii presents a faster response than Filobasidium sp. The toxicity (inhibition of Vibrio fischeri luminescence) of C. laurentii treated WW decreases to an inhibition value below 2.5%. However, treated WW exceeds the legal limits, making necessary an additional treatment. In this case, the selection of Fenton's reagent as a chemical final polish step process is a good compromise between efficiency and lower practical complexity. The best results for both COD and TPP removal were obtained with H2O2 initial concentration of 39.2mM and a H2O2:Fe(2+) molar ratio of 15:1. The combined C. laurentii - Fenton's reagent treatment of WW achieved a total reduction of 98% and 96%, for COD and TPP, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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

Cerebroprotective effect of combined treatment with pyrazidol and bemitil in craniocerebral trauma.

PubMed

Zarubina, I V; Kuritsyna, N A; Shabanov, P D

2004-07-01

Monotherapy of consequences of craniocerebral trauma with pyrazidol (1 mg/kg) produced an anxiolytic effect in animals highly resistant to hypoxia and activating effect on low resistant animals. Treatment with bemitil in a dose of 25 mg/kg produced a cerebroprotective effect and normalized individual behavioral characteristics, parameters of energy metabolism, and state of the antioxidant system in the brain of highly and low resistant rats. The effect of bemitil was most pronounced in highly resistant animals. During combined treatment, pyrazidol and bemitil had an additive effect in animals of both groups. They normalized behavioral reactions and prevented the development of metabolic disturbances in the brain.

Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes

PubMed Central

Reynolds, Jonathan K

2009-01-01

JanumetTM, a fixed dose combination of sitagliptin/metformin HCL manufactured by Merck Pharmaceuticals, has received US Food and Drug Administration approval for treatment of patients with type 2 diabetes, that are inadequately controlled, either by sitagliptin or metformin alone or together in free-dose combination form. Sitagliptin, an inhibitor of the enzyme DDP-4, assists patients with type 2 diabetes mellitus to achieve glycemic control. It has been shown to be safe and effective at 100 mg daily doses. The effect of giving sitagliptin in combination with metformin is thought to have a complimentary and possibly additive effect on glycemic control. PMID:21437126

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

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.

PubMed

Che, Huan-Yong; Guo, Hang-Yuan; Si, Xu-Wei; You, Qiao-Ying; Lou, Wei-Ying

2014-01-01

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy.

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.

Textile wastewater reuse after additional treatment by Fenton's reagent.

PubMed

Ribeiro, Marília Cleto Meirelles; Starling, Maria Clara V M; Leão, Mônica Maria Diniz; de Amorim, Camila Costa

2017-03-01

This study verifies textile wastewater reuse treated by the conventional activated sludge process and subjected to further treatment by advanced oxidation processes. Three alternative processes are discussed: Fenton, photo-Fenton, and UV/H 2 O 2 . Evaluation of treatments effects was based on factorial experiment design in which the response variables were the maximum removal of COD and the minimum concentration of residual H 2 O 2 in treated wastewater. Results indicated Fenton's reagent, COD/[H 2 O 2 ]/[Fe 2+ ] mass ratio of 1:2:2, as the best alternative. The selected technique was applied to real wastewater collected from a conventional treatment plant of a textile mill. The quality of the wastewater before and after the additional treatment was monitored in terms of 16 physicochemical parameters defined as suitable for the characterization of waters subjected to industrial textile use. The degradation of the wastewater was also evaluated by determining the distribution of its molecular weight along with the organic matter fractionation by ultrafiltration, measured in terms of COD. Finally, a sample of the wastewater after additional treatment was tested for reuse at pilot scale in order to evaluate the impact on the quality of dyed fabrics. Results show partial compliance of treated wastewater with the physicochemical quality guidelines for reuse. Removal and conversion of high and medium molecular weight substances into low molecular weight substances was observed, as well as the degradation of most of the organic matter originally present in the wastewater. Reuse tests indicated positive results, confirming the applicability of wastewater reuse after the suggested additional treatment. Graphical abstract Textile wastewater samples after additional treatment by Fenton's reagent, photo-Fenton and H 2 O 2 /UV tested in different conditions.

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.

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.

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

The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

NASA Astrophysics Data System (ADS)

Tang, Yuan; McGoron, Anthony J.

2010-02-01

Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.

PubMed

Vignati, F; Loli, P

1996-08-01

Over the last few years ketoconazole and octreotide have been employed in the treatment of pituitary-dependent or ectopic Cushing's syndrome. In four patients (two men and two women, aged 25-64 yr) with severe ACTH-dependent hypercortisolism in whom medical treatment with ketoconazole showed limited effectiveness and/or tolerability, we tried the association with octreotide. In all patients ketoconazole (200-1000 mg) induced a marked decrease in urinary free cortisol (UFC) excretion, but normalization could not be achieved. After ketoconazole discontinuation, three patients received octreotide alone (300-1500 micrograms/day, sc). This drug caused a dramatic decrease in UFC excretion, although not normalization; in all patients, escape from treatment occurred. Combined treatment was carried out for 10-180 days. Urinary cortisol excretion normalized and remained steadily within normal limits in three of four patients in whom normal UFC excretion had never been attained with both single drug regimens; in the fourth patient, UFC excretion decreased to levels lower than those achieved with ketoconazole or octreotide alone. The association with octreotide allowed a reduction in the daily dose of ketoconazole in three patients. Consistent with the steady reduction of cortisol production, a striking clinical improvement occurred in all patients after starting combined treatment. The normalization of UFC in three of four patients treated with both agents suggests that this approach may be useful in the long term treatment of severe forms of hypercortisolism of both pituitary and ectopic origin. In contrast to the limited effectiveness of each drug taken singularly at the same or higher doses, the association of the two drugs had an additive effect in the attainment of normal urinary cortisol excretion.

Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride.

PubMed

Lee, Sun-Young; Kang, Dong-Hyun

2016-05-01

The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

PubMed

Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

2014-01-01

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

Pediatric Bipolar Disorder: Combination Pharmacotherapy, Adverse Effects, and Treatment of High-Risk Youth.

PubMed

Chang, Kiki D

2016-01-01

Treating bipolar disorder in pediatric patients is challenging because data from rigorous trials of pharmacotherapy in this population are still not plentiful enough. Furthermore, the treatment of children and adolescents is complicated by the frequent need to combine pharmacotherapies to address all bipolar symptoms as well as this population's elevated risk for experiencing side effects. Additionally, young patients with depressive episodes who are at high risk for developing bipolar disorder need careful treatment to prevent or delay the emergence of mania. Despite these challenges, clinicians should evaluate the existing pediatric literature, extrapolate evidence obtained from adult patients, and draw from clinical experience to guide treatment decisions for children and adolescents with bipolar disorder. © Copyright 2016 Physicians Postgraduate Press, Inc.

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…

Optimization of heat treatment parameters for additive manufacturing and gravity casting AlSi10Mg alloy

NASA Astrophysics Data System (ADS)

Girelli, L.; Tocci, M.; Montesano, L.; Gelfi, M.; Pola, A.

2017-11-01

Additive manufacturing of metals is a production process developed in the last few years to realize net shape components with complex geometry and high performance. AlSi10Mg is one of the most widely used aluminium alloys, both in this field and in conventional foundry processes, for its significant mechanical properties combined with good corrosion resistance. In this paper the effect of heat treatment on AlSi10Mg alloy was investigated. Solution and ageing treatments were carried out with different temperatures and times on samples obtained by direct metal laser sintering and gravity casting in order to compare their performance. Microstructural analyses and hardness tests were performed to investigate the effectiveness of the heat treatment. The results were correlated to the sample microstructure and porosity, analysed by means of optical microscopy and density measurements. It was found that, in the additive manufactured samples, the heat treatment can reduce significantly the performance of the alloy also because of the increase of porosity due to entrapped gas during the deposition technique and that the higher the solution temperature the higher the increase of such defects. A so remarkable effect was not found in the conventional cast alloy.

New Nomenclatures for Heat Treatments of Additively Manufactured Titanium Alloys

NASA Astrophysics Data System (ADS)

Baker, Andrew H.; Collins, Peter C.; Williams, James C.

2017-07-01

The heat-treatment designations and microstructure nomenclatures for many structural metallic alloys were established for traditional metals processing, such as casting, hot rolling or forging. These terms do not necessarily apply for additively manufactured (i.e., three-dimensionally printed or "3D printed") metallic structures. The heat-treatment terminology for titanium alloys generally implies the heat-treatment temperatures and their sequence relative to a thermomechanical processing step (e.g., forging, rolling). These designations include: β-processing, α + β-processing, β-annealing, duplex annealing and mill annealing. Owing to the absence of a thermomechanical processing step, these traditional designations can pose a problem when titanium alloys are first produced via additive manufacturing, and then heat-treated. This communication proposes new nomenclatures for heat treatments of additively manufactured titanium alloys, and uses the distinct microstructural features to provide a correlation between traditional nomenclature and the proposed nomenclature.

A Bioengineered Nisin Derivative, M21A, in Combination with Food Grade Additives Eradicates Biofilms of Listeria monocytogenes

PubMed Central

Smith, Muireann K.; Draper, Lorraine A.; Hazelhoff, Pieter-Jan; Cotter, Paul D.; Ross, R. P.; Hill, Colin

2016-01-01

The burden of foodborne disease has large economic and social consequences worldwide. Despite strict regulations, a number of pathogens persist within the food environment, which is greatly contributed to by a build-up of resistance mechanisms and also through the formation of biofilms. Biofilms have been shown to be highly resistant to a number of antimicrobials and can be extremely difficult to remove once they are established. In parallel, the growing concern of consumers regarding the use of chemically derived antimicrobials within food has led to a drive toward more natural products. As a consequence, the use of naturally derived antimicrobials has become of particular interest. In this study we investigated the efficacy of nisin A and its bioengineered derivative M21A in combination with food grade additives to treat biofilms of a representative foodborne disease isolate of Listeria monocytogenes. Investigations revealed the enhanced antimicrobial effects, in liquid culture, of M21A in combination with citric acid or cinnamaldehyde over its wild type nisin A counterpart. Subsequently, an investigation was conducted into the effects of these combinations on an established biofilm of the same strain. Nisin M21A (0.1 μg/ml) alone or in combination with cinnamaldehyde (35 μg/ml) or citric acid (175 μg/ml) performed significantly better than combinations involving nisin A. All combinations of M21A with either citric acid or cinnamaldehyde eradicated the L. monocytogenes biofilm (in relation to a non-biofilm control). We conclude that M21A in combination with available food additives could further enhance the antimicrobial treatment of biofilms within the food industry, simply by substituting nisin A with M21A in current commercial products such as Nisaplin® (Danisco, DuPont). PMID:27965658

[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 chemical-biological treatment for prevention/rehabilitation of clogged wells by an iron-oxidizing bacterium.

PubMed

Gino, Efrat; Starosvetsky, Jeanna; Kurzbaum, Eyal; Armon, Robert

2010-04-15

Groundwater wells containing large concentrations of ferrous iron face serious clogging problems as a result of biotic iron oxidation. Following a short time after their start off, wells get clogged, and their production efficiency drop significantly up to a total obstruction, making cleanup and rehabilitation an economic burden. The present study was undertaken to test an experimental combined treatment (chemical and biological) for future prevention or rehabilitation of clogged wells. Sphaerotilus natans (an iron-oxidizing bacterium) freshly isolated from a deep well was grown to form biofilms on two systems: coupons and sand buried miniature wedge wire screen baskets. A combined chemical-biological treatment, applied at laboratory scale by use of glycolic acid (2%) and isolated bacteriophages against Sphaerotilus natans (SN1 and ER1-a newly isolated phage) at low multiplicity of infection (MOI), showed inhibition of biofilm formation and inactivation of the contaminant bacteria. In addition to complete inactivation of S. natans planktonic bacteria by the respective phages, earlier biofilm treatment with reduced glycolic acid concentration revealed efficient exopolysaccharide (EPS) digestion allowing phages to be increasingly efficient against biofilm matrix bacteria. Utilization of this combined treatment revealed clean surfaces of a model stainless steel wedge wire screen baskets (commonly used in wells) for up to 60 days.

Addition of carbonic anhydrase 9 inhibitor SLC-0111 to temozolomide treatment delays glioblastoma growth in vivo

PubMed Central

Boyd, Nathaniel H.; Walker, Kiera; Fried, Joshua; Hackney, James R.; McDonald, Paul C.; Benavides, Gloria A.; Spina, Raffaella; Audia, Alessandra; Scott, Sarah E.; Libby, Catherine J.; Tran, Anh Nhat; Bevensee, Mark O.; Griguer, Corinne; Nozell, Susan; Gillespie, G. Yancey; Nabors, Burt; Bhat, Krishna P.; Bar, Eli E.; Darley-Usmar, Victor; Xu, Bo; Gordon, Emily; Dedhar, Shoukat; Hjelmeland, Anita B.

2017-01-01

Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor-initiating cell hypothesis. Standard of care for glioblastoma (GBM) includes temozolomide chemotherapy, which is not curative, due, in part, to residual therapy-resistant brain tumor-initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CA9), a hypoxia-responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we explored whether CA9 and CA12 inhibitor SLC-0111 could decrease GBM growth in combination with temozolomide or influence percentages of BTICs after chemotherapy. In multiple GBMs, SLC-0111 used concurrently with temozolomide reduced cell growth and induced cell cycle arrest via DNA damage in vitro. In addition, this treatment shifted tumor metabolism to a suppressed bioenergetic state in vivo. SLC-0111 also inhibited the enrichment of BTICs after temozolomide treatment determined via CD133 expression and neurosphere formation capacity. GBM xenografts treated with SLC-0111 in combination with temozolomide regressed significantly, and this effect was greater than that of temozolomide or SLC-0111 alone. We determined that SLC-0111 improves the efficacy of temozolomide to extend survival of GBM-bearing mice and should be explored as a treatment strategy in combination with current standard of care. PMID:29263302

Combined treatment technology based on synergism between hydrodynamic cavitation and advanced oxidation processes.

PubMed

Gogate, Parag R; Patil, Pankaj N

2015-07-01

The present work highlights the novel approach of combination of hydrodynamic cavitation and advanced oxidation processes for wastewater treatment. The initial part of the work concentrates on the critical analysis of the literature related to the combined approaches based on hydrodynamic cavitation followed by a case study of triazophos degradation using different approaches. The analysis of different combinations based on hydrodynamic cavitation with the Fenton chemistry, advanced Fenton chemistry, ozonation, photocatalytic oxidation, and use of hydrogen peroxide has been highlighted with recommendations for important design parameters. Subsequently degradation of triazophos pesticide in aqueous solution (20 ppm solution of commercially available triazophos pesticide) has been investigated using hydrodynamic cavitation and ozonation operated individually and in combination for the first time. Effect of different operating parameters like inlet pressure (1-8 bar) and initial pH (2.5-8) have been investigated initially. The effect of addition of Fenton's reagent at different loadings on the extent of degradation has also been investigated. The combined method of hydrodynamic cavitation and ozone has been studied using two approaches of injecting ozone in the solution tank and at the orifice (at the flow rate of 0.576 g/h and 1.95 g/h). About 50% degradation of triazophos was achieved by hydrodynamic cavitation alone under optimized operating parameters. About 80% degradation of triazophos was achieved by combination of hydrodynamic cavitation and Fenton's reagent whereas complete degradation was achieved using combination of hydrodynamic cavitation and ozonation. TOC removal of 96% was also obtained for the combination of ozone and hydrodynamic cavitation making it the best treatment strategy for removal of triazophos. 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.

Combination of hyaluronic acid, carmellose, and osmoprotectants for the treatment of dry eye disease

PubMed Central

Mateo Orobia, Antonio José; Saa, Jorge; Ollero Lorenzo, Alberto; Herreras, José María

2018-01-01

Background Dry Eye Disease (DED) is a multifactorial disease, with a high prevalence, that can have a great impact on the quality of life of patients. The first step of treatment includes the use of lacrimal substitutes composed of polymers, possible to associate osmoprotectant agents to the lacrimal substitutes. The aim of this article is to analyze the properties of the combination of hyaluronic acid (HA), carmellose, and osmoprotectors (Optava Fusion®; Allergan, Inc., Irvine, CA, USA) on DED. General considerations on the use of artificial tears are also proposed. Methods A group of ophthalmologists, experts in the management of the ocular surface, analyzed different aspects related to DED; among them, the use of artificial tears in general and the properties of the combination of HA, carmellose, and osmoprotectors, in particular, were discussed. A review of the literature was carried out, which included different articles published in Spanish, English, and French until April 2017. Conclusions DED is a common chronic pathology that usually requires sustained treatment. In addition, the combination of HA, carmellose, and osmoprotectors has proven to be effective in the treatment of symptoms and signs of dry eye by the synergistic action of all its components. This review provides key elements to help ophthalmologists who begin in the management of DED. PMID:29563769

New Laser System For Combined Monitoring And Treatment Of Neonatal Hyperbilirubinemia

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; Hamza, Mohammad

1989-09-01

Laser photoradiation therapy for neonatal hyperbilirubinemia is a breakthrough in the management of neonatal jaundice. In this paper the authors present a new laser system that provides combined monitoring and therapy for neonatal hyperbilirubinemia. The new system incorporates tunable laser sources that can be operated at selected wavelengths to achieve both transcutaneous differential absorption measurements of bilirubin concentration in addition to laser photoradiation therapy. The new laser system can allow the treating physician to avoid over or under treatment of jaundiced neonates by the control of serum bilirubin from a critically high level to a reasonably safe level.

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

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.

Addition of Immunosuppressive Treatment to Hemoperfusion Is Associated with Improved Survival after Paraquat Poisoning: A Nationwide Study

PubMed Central

Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen

2014-01-01

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age. PMID:24475310

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.

[Treatment of Graves Hyperthyroidism by Jiakangling Capsule Combined with Reduction of 131I: an Efficacy Observation].

PubMed

Liu, Guan-xin; Liao, Ning

2016-01-01

To observe the clinical efficacy of Jiakangling Capsule (JC) combined with reduction of 1311 in treatment of Graves hyperthyroidism. Totally 387 Graves hyperthyroidism patients were randomly assigned to the treatment group (200 cases) and the control group (187 cases). Patients in the treatment group took JC combined with reduction of 131I. The 131I dosage per gram of thyroid tissue was 50-80 microCi. They additionally took JC one week after taking 1311 for one consecutive month. Patients in the control group took 131 routinely as one disposable treatment. The 131I dosage per gram of thyroid tissue was 70-120 microCi, without using JC or other anti-thyroid drugs. All patients were reexamined after 24-month treatment. Whether hyperthyroidism was cured, incurred, or permanent was observed. Efficacies of thyroglobulin antibody (TGAb) and thyroid microsome antibody (TMAb) were compared between the two groups. Compared with the control group, the incurred ratio increased in the treatment group [3.2% (6/187) vs. 16.0% (32/200), P < 0.01], the incurred ratio of strong positive TGAb and TMAb patients increased [3.5% (2/57) vs. 27.1% (16/59), P < 0.01], the permanent hypothyroidism ratio decreased [21.1% (12/57) vs. 3.4% (2/59), P < 0.05 ]. JC combined with reduction of 1311 was superior in treating Graves hyperthyroidism induced permanent hypothyroidism than routine 1311 treatment, especially for strong positive TGAb and TMAb patients.

Combination Controversies: Checkpoint Inhibition Alone or in Combination for the Treatment of Melanoma?

PubMed

Warner, Allison Betof; Postow, Michael A

2018-05-15

The immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have dramatically improved outcomes for patients with metastatic melanoma; however, not all patients benefit from monotherapy with these agents. To address this issue, complementary combinations of immunotherapy are increasingly being explored as a strategy to improve outcomes. However, combinatorial approaches come with heightened risk of toxicity. In this review, we highlight combinations for which there are prospective data from clinical trials. The combinations discussed include ipilimumab plus anti-programmed death 1 agents, ipilimumab plus granulocyte-macrophage colony-stimulating factor, checkpoint inhibitor plus talimogene laherparepvec, ipilimumab plus chemotherapy, checkpoint inhibitor plus BRAF/MEK targeted therapy, and checkpoint inhibition plus radiation therapy. We discuss data regarding the efficacy and toxicity of combination therapy, and we identify clinical scenarios that may favor treatment with combination therapy.

Short communication: Effect of whey protein addition and transglutaminase treatment on the physical and sensory properties of reduced-fat ice cream.

PubMed

Danesh, Erfan; Goudarzi, Mostafa; Jooyandeh, Hossein

2017-07-01

The effects of whey protein addition and transglutaminase treatment, alone and in combination, on the physical and sensory properties of reduced-fat ice cream were investigated. Adding whey protein with or without enzyme treatment decreased melting rate, overrun, and hardness of the reduced-fat ice cream; however, the enzyme-treated sample had a higher melting rate and overrun and softer texture. Whey protein-fortified samples showed higher melting resistance, but lower overrun and firmer texture compared with the enzyme-treated sample without added whey protein. Whey protein addition with or without transglutaminase treatment caused an increase in apparent viscosity and a decrease in flow index of the reduced-fat ice cream; nevertheless, the flow behavior of full-fat sample was most similar to the enzyme-treated reduced-fat sample with no added whey protein. Descriptive sensory analyses showed that neither whey protein addition nor transglutaminase treatment significantly influenced the flavor and odor of reduced-fat ice cream, but they both noticeably improved the color and texture of the final product. The results of this study suggest that whey protein addition with transglutaminase treatment improves the physical and sensory properties of reduced-fat ice cream more favorably than does whey protein addition or transglutaminase treatment alone. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2010-01-01

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

Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

PubMed

Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

2012-03-01

Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neural Implications of Psychotherapy, Pharmacotherapy, and Combined Treatment in Major Depressive Disorder

PubMed Central

Schwartz, Thomas L.; Santarsieri, Daniel

2016-01-01

Numerous clinical trials have been conducted to determine the utility of antidepressant treatment (ADT), psychotherapy, and combined psycho-pharmaco-psychotherapy (PPPT) in treating major depressive disorder (MDD). While all approaches have shown benefit over placebo to varying degrees, the parallel neurophysiological mechanisms that underlie their efficacy have received little attention. The authors will review and discuss a growing body of literature that relates the factors of treatment selection and response to the principles of neuromodulation, with emphasis regarding how neuroimaging and other experimental data reinforce the need for personalized MDD treatment. This manuscript and its theoretical approaches were supported by conducting relevant literature searches of MEDLINE and PubMed electronic databases, prioritizing systemic reviews, and randomized clinical trials using selected MeSH terms. The authors conclude that ADT, psychotherapy, and PPPT all create potentially observable neurofunctional changes and argue that additive and synergistic potentiation of these effects in PPPT may produce more sustained symptom relief than with monotherapy alone. PMID:28031623

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

PubMed

Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

2017-07-26

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Evaluating trifluridine + tipiracil hydrochloride in a fixed combination (TAS-102) for the treatment of colorectal cancer.

PubMed

Mulet, N; Matos, I; Noguerido, A; Martini, G; Élez, M E; Argilés, G; Tabernero, J

2018-04-01

Despite major progress in treating advanced colorectal cancer (CRC), prognosis in this population after progression on standard treatment remains dismal and the development of new drugs represents an unmet need. Historically, fluoropyrimidines have played a major role in the treatment of metastatic CRC. TAS-102, a novel combination of trifluridine and tipiracil hydrochloride, has demonstrated improvement in overall survival in the refractory CRC setting, with a safe toxicity profile. Areas covered: A literature review of published clinical studies was performed. Herein, the authors review the pharmacological and clinical data of TAS-102 when used in metastatic CRC, both as a single agent as well as in novel combinations under investigation. Expert opinion: The addition of TAS-102 to the therapeutic armamentarium of metastatic CRC is an encouraging breakthrough considering the demonstrated survival benefit and favorable tolerability profile. Combinations with other agents are under clinical investigation in different settings in an attempt to widen its use. To optimize treatment in today's era of molecular oncology, efforts should be focused on understanding primary and secondary resistance mechanisms, along with the identification of potential biomarkers of response.

Full-scale effects of addition of sludge from water treatment stations into processes of sewage treatment by conventional activated sludge.

PubMed

Luiz, Marguti André; Sidney Seckler, Ferreira Filho; Passos, Piveli Roque

2018-06-01

An emerging practice for water treatment plant (WTP) sludge is its disposal in wastewater treatment plants (WWTP), an alternative that does not require the installation of sludge treatment facilities in the WTP. This practice can cause both positive and negative impacts in the WWTP processes since the WTP sludge does not have the same characteristics as domestic wastewater. This issue gives plenty of information in laboratory and pilot scales, but lacks data from full-scale studies. The main purpose of this paper is to study the impact of disposing sludge from the Rio Grande conventional WTP into the ABC WWTP, an activated sludge process facility. Both plants are located in São Paulo, Brazil, and are full-scale facilities. The WTP volumetric flow rate (4.5 m³/s) is almost three times that of WWTP (1.6 m³/s). The data used in this study came from monitoring the processes at both plants. The WWTP liquid phase treatment analysis included the variables BOD, COD, TSS, VSS, ammonia, total nitrogen, phosphorus and iron, measured at the inlet, primary effluent, mixed liquor, and effluent. For the WWTP solids treatment, the parameters tested were total and volatile solids. The performance of the WWTP process was analyzed with and without sludge addition: 'without sludge' in years 2005 and 2006 and 'with sludge' from January 2007 to March 2008. During the second period, the WTP sludge addition increased the WWTP removal efficiencies for solids (93%-96%), organic matter (92%-94% for BOD) and phosphorus (52%-88%), when compared to the period 'without sludge'. These improvements can be explained by higher feed concentrations combined to same or lower effluent concentrations in the 'with sludge' period. No critical negative impacts occurred in the sludge treatment facilities, since the treatment units absorbed the extra solids load from the WTP sludge. Copyright © 2018 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.

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 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.

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.

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.

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.

Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

PubMed Central

Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens

2016-01-01

Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160596

The combination of compost addition and arbuscular mycorrhizal inoculation produced positive and synergistic effects on the phytomanagement of a semiarid mine tailing.

PubMed

Kohler, J; Caravaca, F; Azcón, R; Díaz, G; Roldán, A

2015-05-01

A field experiment was carried out to assess the effectiveness of combining mycorrhizal inoculation with a native AM fungus (Glomus sp.) and the addition of an urban organic waste compost (OWC) applied at two rates (0.5 and 2.0% (w:w)), with regard to promoting the establishment of Anthyllis cytisoides L. seedlings in a heavy metal polluted mine tailing, as well as stimulating soil microbial functions. The results showed that the combined use of the highest dose of OWC and AM inoculation significantly increased shoot biomass - by 64% - compared to the control value. However, the separate use of each treatment had no effect on the shoot biomass of this shrub species. At the 2% rate, OWC enhanced root colonisation by the introduced fungus as well as soil nutrient content and soil dehydrogenase and ß-glucosidase activities. The combined treatment increased the uptake of Zn and Mn in shoots, although only Zn reached excessive or potentially toxic levels. This study demonstrates that the combination of organic amendment and an AM fungus is a suitable tool for the phytomanagement of degraded mine tailings, although its effectiveness is dependent on the dose of the amendment. Copyright © 2015 Elsevier B.V. All rights reserved.

[Clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in treatment of acute paraquat poisoning].

PubMed

Zhao, Y; Jian, X D

2016-07-20

Objective: To investigate the clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in the treatment of acute paraquat poisoning. Methods: A total of 80 patients with acute paraquat poisoning who were admitted to our hospital were enrolled as study subjects and randomly divided into routine treatment group (38 patients) and traditional Chinese medicine (TCM) group (42 patients) . The patients in the TCM group were given compound monoammonium glycyrrhizinate and dandelion in addition to the treatment in the control group. Serum alanine aminotransferase (ALT) , total bilirubin (TBil) , blood urea nitrogen (BUN) , creatinine (Cr) , and arterial blood lactate (Lac) and partial pressure of oxygen (PaO 2 ) during different time periods on day 3, 7, and 9 of treatment were observed in both groups, and ulceration of oral mucosa, pulmonary fibrosis, multiple organ dysfunction syndrome (MODS) , and mortality were compared between the two groups. Results: On days 3, 7, and 9 of treatment, the routine treatment group had significantly higher serum ALT, TBil, BUN, Cr, and arterial blood Lac than the TCM group. The routine treatment group had significantly lower arterial blood PaO 2 than the TCM group, while the TCM group had significantly lower incidence rates of ulceration of oral mucosa, pulmonary fibrosis, and MODS and a significantly lower mortality rate than the routine treatment group ( P <0.05) . Conclusion: In the treatment of patients with acute paraquat poisoning, compound monoammonium glycyrrhizinate combined with dandelion can effectively improve organ function, reduce the incidence of pulmonary fibrosis and MODS, improve the healing rate of oral ulcer, improve prognosis, and reduce mortality rate.

Combined Treatment on the Inactivation of Naturally Existing Bacteria and Escherichia coli O157:H7 Inoculated on Fresh-Cut Kale.

PubMed

Kang, Ji Hoon; Song, Kyung Bin

2017-02-28

An aqueous chlorine dioxide (ClO₂) treatment combined with highly activated calcium oxide (CaO) and mild heat was tested for inactivating naturally existing bacteria and Escherichia coli O157:H7 inoculated on fresh-cut kale. Kale samples were treated with different concentrations of ClO₂ (10, 30, and 50 ppm), CaO (0.01%, 0.05%, 0.1%, and 0.2%), and mild heat (25°C, 45°C, 55°C, and 65°C) as well with combinations of 30 or 50 ppm ClO₂ and 0.2% CaO at 55°C for 3 min. An increasing concentration of ClO₂ and CaO significantly reduced the microbialpopulation compared with the control. In addition, mild heating at 55°C elicited greater microbial reduction than the other temperatures. A combined treatment of 50 ppm ClO₂ and 0.2% CaO at 55°C reduced the population of naturally existing bacteria on kale by 3.10 logcolony forming units (CFU)/g, and the counts of E. coli O157:H7 were below the detection limit (1 log CFU/g). In addition, no significant differences in the Hunter color values were evident in any treatment during storage. Therefore, a combined treatment of ClO₂ and active CaO at 55°C can be an effective sanitizing method to improve the microbiological safety of fresh-cut kale without affecting its quality.

Effect of combined treatment with diuretics and gabapentin on convulsive threshold in mice.

PubMed

Łukawski, Krzysztof; Swiderska, Grajyna; Czuczwar, Stanisław J

2013-01-01

Research data show that diuretics can have anticonvulsant properties. This study examined effects of ethacrynic acid, a loop diuretic, and hydrochlorothiazide, a thiazide-type diuretic, on the anticonvulsant activity of gabapentin, a newer antiepileptic drug, in the maximal electroshock seizure threshold test in mice. Diuretics were administered intraperitoneally (ip.) both acutely (single dose) and chronically (once daily for seven days). Electroconvulsions were produced by an alternating current (50 Hz, 500 V, 0.2 s stimulus duration) delivered via ear-clip electrodes by a generator. Additionally, the influence of combined treatment with the diuretics and gabapentin on motor performance in the chimney test has been assessed. In the current study, ethacrynic acid at the chronic dose of 12.5 mg/kg and the single dose of 100 mg/kg did not affect the anticonvulsant activity of gabapentin. Similarly, hydrochlorothiazide (100 mg/kg), both in acute and chronic experiments, had no effect on the gabapentin action. On the other hand, in the chimney test, the combined treatment with ethacrynic acid (100 mg/kg) and gabapentin (50 mg/kg) significantly impaired motor performance in mice. Based on the current preclinical findings, it can be suggested that the diuretics should not affect the anticonvulsant action of gabapentin in epileptic patients. However, the combination of ethacrynic acid with gabapentin may cause neurotoxicity.

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.

Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model

NASA Astrophysics Data System (ADS)

Menyaev, Yulian A.; Zharov, Vladimir P.

2006-02-01

One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 μm wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.

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

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.

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),…

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

PubMed

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

2013-02-01

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

[Amplipulse-magnetotherapy and iodine-bromine waters in combined treatment of patients with chronic nonspecific salpingo-oophoritis].

PubMed

Iarustovskaia, O V; Rodina, E V; Orekhova, E M; Markina, L P

2005-01-01

Amplipulse-magnetotherapy was used as monotherapy and in combined treatment of 110 patients with chronic nonspecific salpingo-oophoritis (CNSO). Clinical assessment shows that transcerebral amplipulse-megnetotherapy (TAMT) has a positive effects on the course of CNSO, reproductive system and psychoemotional status of the patients. The addition of physical and balneological factors to TAMT enhances and prolongs neurotropic, endocrine, analgetic and anti-inflammatory effects of TAMT.

Combined effects of solar ultraviolet radiation and nutrients addition on growth, biomass and taxonomic composition of coastal marine phytoplankton communities of Patagonia.

PubMed

Marcoval, M Alejandra; Villafañe, Virginia E; Helbling, E Walter

2008-05-29

Experiments (6-8 days) were conducted during late summer, late fall and late winter, 2003 with waters collected off Bahía Nueva, Chubut, Argentina (42.7 degrees S, 65 degrees W) to determine the combined effects of solar ultraviolet radiation (UVR, 280-400 nm) and nutrient addition on phytoplankton communities. Samples were put in UVR-transparent containers and incubated under two radiation treatments: (a) Samples exposed to full solar radiation (PAB treatment, 280-400 nm) and (b) Samples exposed only to PAR (PAR treatment, 400-700 nm). At the beginning of the experiments, nutrients (i.e., NaPO(4)H(2) and NaNO(3)) were added to one set of samples from each radiation treatment (N cultures) whereas in the other set, nutrients remained at the concentration of the seawater. Chlorophyll a, biomass, UV-absorbing compounds and taxonomic composition were recorded throughout the experiments. N cultures always had significantly higher growth rates (P<0.05) than that in non-enriched cultures. At the beginning of experiments, phytoplankton communities were generally dominated by monads and flagellates but by the end, diatoms comprised the bulk of biomass, with only one to four taxa dominating, suggesting a selection towards more tolerant/less sensitive species. Over the experimental time frame, the observed taxonomic changes were mostly due to nutrient availability, and to a lesser extent to solar UVR exposure. Overall, the results indicate that environmental conditions (i.e., light history, nutrient concentration) together with the physiological status of the cells play a very important role at the time to assess the combined effect of nutrient addition and solar radiation on coastal phytoplankton assemblages from Patagonia.

Combined use of ultrasonic liposuction with the pull-through technique for the treatment of gynecomastia.

PubMed

Hammond, Dennis C; Arnold, Jame F; Simon, Amy M; Capraro, Philippe A

2003-09-01

The authors present a method of treatment for gynecomastia that combines the use of two techniques of soft-tissue contouring. This method uses ultrasonic liposuction in conjunction with the pull-through technique of direct excision to effectively remove the fibrofatty tissue of the male breast and the fibrous breast bud through a single 1-cm incision. Fifteen patients were treated in this fashion, and each patient demonstrated a smooth, masculine breast contour with a well-concealed scar, which eliminates the stigma of breast surgery. The procedure is technically straightforward and provides consistent results. It is offered as an additional option for the treatment of gynecomastia.

Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

PubMed

Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

2017-01-01

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale

PubMed Central

Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

2016-01-01

Background In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. Methods The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. Results The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. Conclusions The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification. PMID:27045168

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.

Acute toxicity of two generic drilling fluids and six additives, alone and combined, to mysids (Mysidopsis bahia)

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

Parrish, P.R.; Macauley, J.M.; Montgomery, R.M.

1988-01-01

Toxicity tests were conducted with two laboratory-prepared generic drilling fluids (muds) and six commonly used drilling-fluid additives to determine their toxicity, alone and combined, to mysids (Mysidopsis bahia). In 25 tests, the acute toxicity of combinations of one, two, or three of the drilling-fluid additives mixed with either drilling fluid was less than the toxicity predicted from the empirical 96-h LC50s for drilling fluid additive(s) and/or drilling fluid alone; the observed 96-h LC50s of the mixtures were from 1.3 to 23.6 times the values predicted from the presumption of additive toxicity.

Tolerance development in Listeria monocytogenes-Escherichia coli dual-species biofilms after sublethal exposures to pronase-benzalkonium chloride combined treatments.

PubMed

Rodríguez-López, Pedro; Cabo, Marta López

2017-10-01

This study was designed to assess the effects that sublethal exposures to pronase (PRN) and benzalkonium chloride (BAC) combined treatments have on Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel in terms of tolerance development (TD) to these compounds. Additionally, fluorescence microscopy was used to observe the changes of the biofilm structure. PRN-BAC exposure was carried out using three different approaches and TD was evaluated treating biofilms with a final 100 μg/ml PRN followed by 50 μg/ml BAC combined treatment. Results showed that exposure to PRN-BAC significantly decreased the number of adhered L. monocytogenes (P < 0.05), while E. coli counts remained generally unaltered. It was also demonstrated that the incorporation of recovery periods during sublethal exposures increased the tolerance of both species of the mixed biofilm to the final PRN-BAC treatment. Moreover, control biofilms became more resistant to PRN-BAC if longer incubation periods were used. Regardless of the treatment used, log reduction values were generally lower in L. monocytogenes compared to E. coli. Additionally, microscopy images showed an altered morphology produced by sublethal PRN-BAC in exposed L. monocytogenes-E. coli dual-species biofilms compared to control samples. Results also demonstrated that L. monocytogenes-E. coli dual-species biofilms are able to develop tolerance to PRN-BAC combined treatments depending on way they have been previously exposed. Moreover, they suggest that the generation of bacterial tolerance should be included as a parameter for sanitation procedures design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication.

PubMed

Bell, Todd M; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Carey, Brian D; Lin, Shih-Chao; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A; Bailey, Charles L; Kehn-Hall, Kylene

2018-04-13

Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

PubMed Central

Bell, Todd M.; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A.; Bailey, Charles L.

2018-01-01

Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection. PMID:29652799

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.

A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib

PubMed Central

YERLIKAYA, AZMI; ERDOĞAN, ELIF; OKUR, EMRAH; YERLIKAYA, ŞERIFE; SAVRAN, BIRCAN

2016-01-01

Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study first examined the dose- and time-dependent effects of bortezomib on GRP78 expression levels in the highly metastatic mouse breast cancer 4T1 cell line using western blot analysis. The analysis results revealed that GRP78 levels were significantly increased by bortezomib at a dose as low as 10 nM. Time-dependent experiments indicated that the accumulation of GRP78 was initiated after a 24 h incubation period following the addition of 10 nM bortezomib. Subsequently, the present study determined the half maximal inhibitory concentration of intracellular calcium chelator BAPTA-AM (13.6 µM) on 4T1 cells. The combination effect of BAPTA-AM and bortezomib on the 4T1 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and WST-1 assays and an iCELLigence system. The results revealed that the combination of 10 nM bortezomib + 5 µM BAPTA-AM is more cytotoxic compared with monotherapies, including 10 nM bortezomib, 1 µM BAPTA-AM and 5 µM BAPTA-AM. In addition, the present results revealed that bortezomib + BAPTA-AM combination causes cell death through the induction of apoptosis. The present results also revealed that bortezomib + BAPTA-AM combination-induced apoptosis is associated with a clear increase in the phosphorylation of stress-activated protein kinase/Jun amino-terminal kinase SAPK/JNK. Overall, the present results suggest that bortezomib and BAPTA-AM combination therapy may be a novel therapeutic strategy for breast cancer treatment

Orally administered rapamycin, dacarbazine or both for treatment of human melanoma evaluated in severe combined immunodeficiency mice.

PubMed

Thallinger, Christiane; Skorjanec, Sophie; Soleiman, Afschin; Tzaneva, Stanislava; Griss, Johannes; Rous, Wolfgang; Poeppl, Wolfgang; Weinlich, Georg; Karimian-Teherani, Daniela; Joukhadar, Christian

2008-01-01

In this experimental study, the antineoplastic potential of orally administered rapamycin in human melanoma was evaluated and compared with dacarbazine (DTIC) as well as with the antineoplastic effect of the combination of both drugs. The substances were tested using 2 human melanoma cell lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately susceptible. A human melanoma severe combined immunodeficiency mouse xenotransplantation model was used. After development of palpable tumors, mice received oral rapamycin or saline over 18 days. Additionally, from treatment day 4 to 8, mice were randomly chosen to receive either DTIC or saline treatment. The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in 607B xenografts, no significant tumor weight reduction was observed compared with the saline group (p > 0.05). The combination of rapamycin and DTIC was not superior to rapamycin monotreatment in any cell line. These data indicate that oral rapamycin exerts a relevant antineoplastic effect on human melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive melanoma xenografts. Copyright 2008 S. Karger AG, Basel.

Combination treatments for killing Escherichia coli O157:H7 on alfalfa, radish, broccoli, and mung bean seeds.

PubMed

Bari, M L; Nei, D; Enomoto, K; Todoriki, S; Kawamoto, S

2009-03-01

In this study, the effectiveness of prolonged dry-heat treatment (50 degrees C) alone or in combination with chemical treatments (1% oxalic acid, 0.03% phytic acid, 50% ethanol, electrolyzed acidic water, and electrolyzed alkaline water) in eliminating Escherichia coli O157:H7 on laboratory-inoculated alfalfa, radish, broccoli, and mung bean seeds was compared with that of dry-heat treatment in combination with irradiation treatment. Dry-heat treatment for 17 or 24 h alone could reduce E. coli O157:H7 numbers to below detectable levels in radish, broccoli, and alfalfa seeds, but was unable to reduce the pathogen numbers to below the detectable level in mung bean seeds. In addition, dry-heat treatment for 17 h plus sanitizer treatments were effective in greatly reducing pathogen populations on radish, broccoli, and alfalfa seeds, without compromising the quality of the sprouts, but these treatments did not eliminate the pathogen from radish and alfalfa seeds. Seventeen hours of dry heat followed by a 1.0-kGy dose of irradiation completely eliminated E. coli O157:H7 from radish and mung bean seeds, whereas only a minimum radiation dose of 0.25 kGy was required to completely eliminate the pathogen from broccoli and alfalfa seeds. Dry heat in combination with radiation doses of up to 1.0 kGy did not negatively impact the seed germination rate or length of alfalfa, broccoli, and radish seeds or the length of alfalfa, broccoli, and radish sprouts, but did decrease the length of mung bean sprouts.

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.

[Combination therapy in the medical treatment of glaucoma].

PubMed

Hommer, A

2013-02-01

A combination of antiglaucoma medications is indicated if monotherapy is not sufficient to achieve the predefined target pressure and/or in case of a progression of glaucomatous damage or conversion from ocular hypertension to glaucomatous optic neuropathy. Most recently many fixed combinations with two active compounds have become available for the medical treatment of glaucoma. Compared to non-fixed combinations, these drugs offer a much easier use for the patients. Fixed combinations have to be applied less frequently which may improve adherence. Furthermore, they most likely contain a lower amount of toxic preservatives compared to non-fixed combinations. And finally, fixed combinations may eliminate the risk of a "washout" of the first medication by using the second product of a non-fixed combination too soon after the first drop has been installed. This review aims to examine the most important aspects of IOP-lowering fixed and non-fixed combinations in glaucoma management with a clear focus on the results obtained with fixed combinations. In Germany, fixed combinations with the compositions dorzolamide/timolol (FCDT), brinzolamide/timolol (FCBRINT), latanoprost/timolol (FCLT), travoprost/timolol (FCTT), bimatoprost/timolol (FCBIMT), brimonidine/timolol (FCBT), pilocarpine/timolol (FCPT) and metipranolol/timolol (FCMT) are approved for the medical management of glaucoma and ocular hypertension. The results of clinical studies comparing fixed combinations with their active ingredients and with the corresponding non-fixed combinations will be discussed. Furthermore - if available - the results of direct comparisons of the efficacy and safety of different IOP-lowering fixed combinations are summarised. Georg Thieme Verlag KG Stuttgart · New York.

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

Effect of combinations of additives on the performance of lithium ion batteries

NASA Astrophysics Data System (ADS)

Santee, Stuart; Xiao, Ang; Yang, Li; Gnanaraj, Joe; Lucht, Brett L.

Commercial lithium-ion batteries have excellent performance at room temperature for a few years. However, the calendar life and thermal stability (>50 °C) need to be improved for many applications, including electric vehicles. We have conducted an investigation of the effect of thermal stabilizing additives, including dimethyl acetamide, vinylene carbonate, and lithium bis(oxalato) borate, on the performance of lithium ion batteries stored at 70 °C for one month. The reactions of the lithium hexafluorophosphate/carbonate electrolyte, with and without electrolyte additives, with the surface of the electrodes after initial formation cycling have been analyzed via a combination of IR-ATR and XPS.

Research: Treatment Study to determine the durability of glycaemic control with early treatment with a vildagliptin–metformin combination regimen vs. standard-of-care metformin monotherapy—the VERIFY trial: a randomized double-blind trial

PubMed Central

Del Prato, S; Foley, J E; Kothny, W; Kozlovski, P; Stumvoll, M; Paldánius, P M; Matthews, D R

2014-01-01

Aims Durability of good glycaemic control (HbA1c) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows β-cell deterioration as measured by HbA1c. Methods Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48–58 mmol/mol (6.5–7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin–metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. Summary VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria. PMID:24863949

Combination pharmacotherapy for the treatment of fibromyalgia in adults.

PubMed

Thorpe, Joelle; Shum, Bonnie; Moore, R Andrew; Wiffen, Philip J; Gilron, Ian

2018-02-19

Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects. To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults. We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries. Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain. From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table. We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200

Effects of Combining Na and Sr additions on Eutectic Modification in Al-Si alloy

NASA Astrophysics Data System (ADS)

Zhu, G. L.; Gu, N. J.; Zhou, B. J.

2017-09-01

Experiments were designed to investigate the effects of strontium and sodium modified on the eutectic silicon for Al-Si alloy. It was found that combining addition of Na and Sr did not appear to cause deleterious interactions of modification, at at the same time, Sr-Na was fairly constant with holding time and without obvious modification fading. Addition of Na-Sr modifier could take effect quickly and decrease incubation period.

Induction of micronuclei in V79 cells after combined treatments with heterocyclic aromatic amines.

PubMed

Perez, C; Lopez de Cerain, A; Bello, J

2002-10-01

Heterocyclic aromatic amines (HAs) appear in foods rich in proteins when subjected to different cooking processes. These amines have been demonstrated to be mutagenic in bacteria; in eucaryotic cells, controversial results have been referred. The objective of this study is to evaluate the clastogenic and/or aneugenic capacity of three HAs--2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), and 2-amino-3-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)--in isolated as well as in combined treatments. The micronucleus test in vitro was used on V79 cells in the presence and absence of metabolic activation. The duration of the treatment was 2 h, and cytochalasin B was added for 21 h to stop cytokinesis; then, micronuclei (MN) were counted in binucleated cells. In the presence of metabolic activation, the three amines showed a significant increase in the number of MN with respect to the negative control. The PhIP amine presented the highest values and it also resulted slightly active in the absence of metabolic activation, although these differences have not been considered to be significant. The combined treatments of these amines have shown that the effects attributed to them when administered together are those that are expected for a possible additive effect; the effect attributed to each HA separately is not potentiated nor inhibited.

Potentiating action of 5-fluorouracil when used in combination with platinium compounds and cyclophosphamide in treatment of advanced L1210 leukemia.

PubMed

Gale, G R; Atkins, L M; Schwartz, P; Meischen, S J

1978-01-01

Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (greater than 60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

Combined clopidogrel-aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds.

PubMed

Wang, Zhiming; Xu, Chenghua; Wang, Peng; Wang, Yilong; Xin, Huaping

2015-11-01

To study whether Clopidogrel-Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment. The patients recruited in CHANCE test in our hospital participated in this study. We made a comparison between treatments Aspirin-Clopidogrel combined group and the Aspirin alone group in the numbers of CMB and subsequent cerebral haemorrhages. In addition, we analysed the association between the increased numbers of CMB and subsequent intracerebral haemorrhages. All 129 patients with high risk TIA with microbleeds or minor stroke within 24 hours after the onset (average age 65.9 ± 9.3, 48.7% were male patients) were divided randomly into two groups: (1) 67 patients were given combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, then 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days);(2) the rest patients were given aspirin treatment (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75-300 mg on the first day. The CMB were found in 52.7% of all patients in both groups. There was no siginificant difference between the Aspirin group and the Aspirin-clopidogrel treated group, though the latter showed some slight increase in CMB (Odds ratios (OR) = 1.16, 95% confidence intervals (CI) = 0.54-2.47, P = 0.71). But the numbers of CMB were remarkably associated with the number of primary existing CMB (OR = 6.46, 95%CI 2.57-16.23, P < 0.001), especially that of primary existing CMB ≥  3.In addition, the increasing numbers of CMB associated with primary CMB lesions, which located in corticosubcortical area (CSC) (OR = 4.69, 95%CI 1.51-14.53, P = 0.007). For the treatment of high-risk TIA or minor stroke patients, the

Combination treatment of chlorine dioxide gas and aerosolized sanitizer for inactivating foodborne pathogens on spinach leaves and tomatoes.

PubMed

Park, Sang-Hyun; Kang, Dong-Hyun

2015-08-17

The objective of this study was to evaluate the antimicrobial effect of chlorine dioxide (ClO2) gas and aerosolized sanitizer, when applied alone or in combination, on the survival of Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes inoculated onto spinach leaves and tomato surfaces. Spinach leaves and tomatoes were inoculated with a cocktail of three strains each of the three foodborne pathogens. ClO2 gas (5 or 10 ppmv) and aerosolized peracetic acid (PAA) (80 ppm) were applied alone or in combination for 20 min. Exposure to 10 ppmv of ClO2 gas for 20 min resulted in 3.4, 3.3, and 3.4 log reductions of E. coli O157:H7, S. Typhimurium, and L. monocytogenes on spinach leaves, respectively. Treatment with 80 ppm of aerosolized PAA for 20 min caused 2.3, 1.9, and 0.8 log reductions of E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively. Combined treatment of ClO2 gas (10 ppmv) and aerosolized PAA (80 ppm) for 20 min caused 5.4, 5.1, and 4.1 log reductions of E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively. E. coli O157:H7, S. Typhimurium, and L. monocytogenes on tomatoes experienced similar reduction patterns to those on spinach leaves. As treatment time increased, most combinations of ClO2 gas and aerosolized PAA showed additive effects in the inactivation of the three pathogens. Combined treatment of ClO2 gas and aerosolized PAA produced injured cells of three pathogens on spinach leaves while generally did not produce injured cells of these pathogens on tomatoes. Combined treatment of ClO2 gas (10 ppmv) and aerosolized PAA (80 ppm) did not significantly (p>0.05) affect the color and texture of samples during 7 days of storage. Copyright © 2015. Published by Elsevier B.V.

Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid.

PubMed

Chiu, Chih-Tung; Kuo, Sheng-Nan; Hung, Shao-Wen; Yang, Cheng-Yao

2017-05-30

Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA) and 5-ASA (IBD98-M). HA-fluoresceinamine (FL) conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis.

Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions.

PubMed

Andia, Isabel; Abate, Michele

2018-04-01

Current research on common musculoskeletal problems, including osteoarticular conditions, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients' outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rich plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.

Additive treatment improves survival in elderly patients after non-curative endoscopic resection for early gastric cancer.

PubMed

Jung, Da Hyun; Lee, Yong Chan; Kim, Jie-Hyun; Lee, Sang Kil; Shin, Sung Kwan; Park, Jun Chul; Chung, Hyunsoo; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin

2017-03-01

Endoscopic resection (ER) is accepted as a curative treatment option for selected cases of early gastric cancer (EGC). Although additional surgery is often recommended for patients who have undergone non-curative ER, clinicians are cautious when managing elderly patients with GC because of comorbid conditions. The aim of the study was to investigate clinical outcomes in elderly patients following non-curative ER with and without additive treatment. Subjects included 365 patients (>75 years old) who were diagnosed with EGC and underwent ER between 2007 and 2015. Clinical outcomes of three patient groups [curative ER (n = 246), non-curative ER with additive treatment (n = 37), non-curative ER without additive treatment (n = 82)] were compared. Among the patients who underwent non-curative ER with additive treatment, 28 received surgery, three received a repeat ER, and six experienced argon plasma coagulation. Patients who underwent non-curative ER alone were significantly older than those who underwent additive treatment. Overall 5-year survival rates in the curative ER, non-curative ER with treatment, and non-curative ER without treatment groups were 84, 86, and 69 %, respectively. No significant difference in overall survival was found between patients in the curative ER and non-curative ER with additive treatment groups. The non-curative ER groups were categorized by lymph node metastasis risk factors to create a high-risk group that exhibited positive lymphovascular invasion or deep submucosal invasion greater than SM2 and a low-risk group without risk factors. Overall 5-year survival rate was lowest (60 %) in the high-risk group with non-curative ER and no additive treatment. Elderly patients who underwent non-curative ER with additive treatment showed better survival outcome than those without treatment. Therefore, especially with LVI or deep submucosal invasion, additive treatment is recommended in patients undergoing non-curative ER, even if they are

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.

PubMed

Lev, Avital; Deihimi, Safoora; Shagisultanova, Elena; Xiu, Joanne; Lulla, Amriti R; Dicker, David T; El-Deiry, Wafik S

2017-09-02

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared with BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared with each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006-0.74). However, we found no evidence for c-MET upregulation upon effective BRCA2 knockdown in tumor cells -/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.

Summary of combined treatment under endoscope on 70 esophagus cancer inpatients

NASA Astrophysics Data System (ADS)

Wang, Cheng; Nong, Meilong; Li, Laisheng; Jia, Fang; Hao, Runchun

1993-03-01

We announce with satisfaction that combined treatment on 70 inpatients who suffered esophageal cancer in its middle or late course is perfectly successful. The combined methods include phototherapy, microwave therapy, and anticarcinogen local injection. The results are as follows: CR 3 cases, holds 4.3% of the total inpatients; PR 36 cases, 51.4%; MR 24 cases, 34.3%; NR 7 cases, 10%; the total effective rate 90%. Splendid results of treatment on enlarging the canal, improving dysphagia, and releasing obstruction have been obtained. The dysphagic grade increased from 66 to 148, the grade of esophagostenosis from 64 to 147, and the obstruction releasing rate is 69 out of 70 (that is 98.6%). The histological observation after treatment shows that 59/62 inpatients being reported as having cancer cells appear to have retrogression accompanied with a few or large quantities of necrotic cancer cells, and 3 inpatients were changed to negative reaction. No obvious poisoning or side effects arose. The combined treatment is more advantageous on those of old age or the physically weak and those who cannot stand for an operation, radiotherapy, or normal chemotherapy.

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.

Combined treatment with electrical stimulation and insulin-like growth factor-1 promotes bone regeneration in vitro.

PubMed

Qi, Zhiping; Xia, Peng; Pan, Su; Zheng, Shuang; Fu, Chuan; Chang, Yuxin; Ma, Yue; Wang, Jincheng; Yang, Xiaoyu

2018-01-01

Electrical stimulation (ES) and insulin-like growth factor-1 (IGF-1) are widely used in bone regeneration because of their osteogenic activity. However, the combined effects of ES and supplemental IGF-1 on the whole bone formation process remain unclear. In this study, fluorescence staining and an MTT assay were first utilized to observe the influence of ES and IGF-1 on MC3T3-E1 cell proliferation and adhesion in vitro. Subsequently, osteogenic differentiation was evaluated by the alkaline phosphatase activity (ALP) and the expression of osteogenic marker genes. In addition, cell mineralization was determined by alizarin red staining and scanning electron microscopy (SEM). We demonstrated that the MC3T3-E1 cell proliferation was significantly higher for treatments combining IGF-1 and ES than for treatments with IGF-1 alone. The combination of IGF-1 and ES increased the MC3T3-E1 cell ALP activity, the expression of osteogenesis-related genes and the calcium deposition with a clear dose-dependent effect. Our data show the synergistic effect of IGF-1 and ES in promoting the proliferation, differentiation and mineralization of MC3T3-E1 cells, which suggests that it would be more effective to combine the proper dose of IGF-1 with ES to promote local bone damage repair and regeneration.

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.

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.

[Treatment of Occipital Neuralgia by Electroacupuncture Combined with Neural Mobilization].

PubMed

Wang, Yan; Guo, Zi-Nan; Yang, Zhen; Wang, Shun

2018-03-25

To observe the effect of electroacupuncture (EA) combined with neural mobilization (NM) in the treatment of occipital neuralgia. A total of 62 occipital neuralgia patients were randomized into EA group (19 cases), NM group (22 cases) and EA＋NM group (21 cases). EA was applied at acupoint-pairs as Yuzhen (BL 9)- Tianzhu (BL 10), Fengchi (GB 20)- Wangu (GB 12), etc. NM intervention consisted of occipital muscle group mobilization, C 2 spinous process mobilization, cervical joint passive movement management mobilization, etc., was performed at the impaired cervical spine segment. The two methods were used in combination for patients in the EA＋NM group. All the treatment was given once a day for 2 weeks. Before and after treatment, the visual analogue scale (VAS) and the 6-point (1－6 points) behavioral rating scale (BRS-6) of headache were used to assess the severity of pain. The therapeutic effect was evaluated according to the "Criteria for Diagnosis and Cure-Improvement of Clinical Conditions" formulated by State Administration of Traditional Chinese Medicine of the People's Republic of China in 1994. After treatment, both VAS and BRS-6 scores were significantly lower than those before treatment in each of the three groups ( P <0.05), and were significantly lower in the EA＋NM group than in the simple EA and simple NM groups ( P <0.01, P <0.05). The total effective rates were 78.95% (15/19) in the EA group, 68.18% (15/22) in the NM group, and 90.48% (19/21) in the EA＋NM group, with an obviously better therapeutic effect being in the EA＋NM group relevant to each of the other two treatment groups ( P <0.05). EA, NM and EA combined with NM can improve symptoms of patients with occipital neuralgia, and EA＋NM has a synergic analgesic effect for occipital neuralgia.

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

PubMed

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

2012-04-01

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

Combination irradiation treatments for food safety and phytosanitary uses

USDA-ARS?s Scientific Manuscript database

Combination of irradiation treatment with other preservation techniques is of potential importance in enhancing the effectiveness and reducing the energy or dose requirement for destroying food borne illness and spoilage organisms while retaining or improving product quality. Phytosanitary irradiati...

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.

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

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

Lelieveld, P.; Scoles, M.A.; Brown, J.M.

1985-01-01

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

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.

A combined electrochemical-irradiation treatment of highly colored and polluted industrial wastewater

NASA Astrophysics Data System (ADS)

Barrera-Díaz, C.; Ureña-Nuñez, F.; Campos, E.; Palomar-Pardavé, M.; Romero-Romo, M.

2003-07-01

This study reports on the attainment of optimal conditions for two electrolytic methods to treat wastewater: namely, electrocoagulation and particle destabilization of a highly polluted industrial wastewater, and electrochemically induced oxidation induced by in situ generation of Fenton's reactive. Additionally, a combined method that consisted of electrochemical treatment plus γ-irradiation was carried out. A typical composition of the industrial effluent treated was COD 3400 mg/l, color 3750 Pt/Co units, and fecal coliforms 21000 MPN/ml. The best removal efficiency was obtained with electrochemical oxidation induced in situ , that resulted in the reduction of 78% for the COD, 86% color and 99.9% fecal coliforms removal. A treatment sequence was designed and carried out, such that after both electrochemical processes, a γ-irradiation technique was used to complete the procedure. The samples were irradiated with various doses in an ALC γ-cell unit provided with a Co-60 source. The removal efficiency obtained was 95% for the COD values, 90% color and 99.9% for fecal coliforms.

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors.

PubMed

Güllü, I H; Celik, I; Tekuzman, G; Altunbaş, M; Güler, N; Barişta, I; Alkiş, N; Yalçin, S; Kars, A; Baltali, E; Kansu, E; Firat, D

1996-01-01

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

PubMed Central

Hsu, Yun-Ting; Huang, Jung-Tang; Wu, T. -C; Hung, Chien-Fu; Yang, Yuh-Cheng; Chang, Chih-Long

2013-01-01

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer. PMID:23935988

Efficient Improvement of Silage Additives by Using Genetic Algorithms

PubMed Central

Davies, Zoe S.; Gilbert, Richard J.; Merry, Roger J.; Kell, Douglas B.; Theodorou, Michael K.; Griffith, Gareth W.

2000-01-01

The enormous variety of substances which may be added to forage in order to manipulate and improve the ensilage process presents an empirical, combinatorial optimization problem of great complexity. To investigate the utility of genetic algorithms for designing effective silage additive combinations, a series of small-scale proof of principle silage experiments were performed with fresh ryegrass. Having established that significant biochemical changes occur over an ensilage period as short as 2 days, we performed a series of experiments in which we used 50 silage additive combinations (prepared by using eight bacterial and other additives, each of which was added at six different levels, including zero [i.e., no additive]). The decrease in pH, the increase in lactate concentration, and the free amino acid concentration were measured after 2 days and used to calculate a “fitness” value that indicated the quality of the silage (compared to a control silage made without additives). This analysis also included a “cost” element to account for different total additive levels. In the initial experiment additive levels were selected randomly, but subsequently a genetic algorithm program was used to suggest new additive combinations based on the fitness values determined in the preceding experiments. The result was very efficient selection for silages in which large decreases in pH and high levels of lactate occurred along with low levels of free amino acids. During the series of five experiments, each of which comprised 50 treatments, there was a steady increase in the amount of lactate that accumulated; the best treatment combination was that used in the last experiment, which produced 4.6 times more lactate than the untreated silage. The additive combinations that were found to yield the highest fitness values in the final (fifth) experiment were assessed to determine a range of biochemical and microbiological quality parameters during full-term silage

Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse.

PubMed

Sushchyk, Sarah; Xi, Zheng-Xiong; Wang, Jia Bei

2016-05-01

Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects ofl-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination ofl-THP and LDN reduces drug-seeking behavior during reinstatement more potently thanl-THP alone. Additionally, the combination ofl-THP and LDN attenuates the sedative locomotor effect induced byl-THP. Furthermore, we revealed that treatment with the combination ofl-THP and LDN has an upregulatory effect on both plasmaβ-endorphin and hypothalamic POMC that was not observed inl-THP-treated groups. These results suggest that the combination ofl-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention. U.S. Government work not protected by U.S. copyright.

Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse

PubMed Central

Sushchyk, Sarah; Xi, Zheng-Xiong

2016-01-01

Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects of l-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination of l-THP and LDN reduces drug-seeking behavior during reinstatement more potently than l-THP alone. Additionally, the combination of l-THP and LDN attenuates the sedative locomotor effect induced by l-THP. Furthermore, we revealed that treatment with the combination of l-THP and LDN has an upregulatory effect on both plasma β-endorphin and hypothalamic POMC that was not observed in l-THP-treated groups. These results suggest that the combination of l-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention. PMID:26903543

Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw?

PubMed

Park, Jung-Hyun; Kim, Jin-Woo; Kim, Sun-Jong

2017-06-01

To investigate the effect of the addition of bone morphogenetic protein 2 (BMP-2) to leukocyte-rich and platelet-rich fibrin (L-PRF) on the treatment of medication-related osteonecrosis of the jaws (MRONJ), this study compared the healing outcome of combined use of BMP-2 and L-PRF with single use of L-PRF. Of 55 patients who were diagnosed with MRONJ, 25 were treated with L-PRF alone and 30 were treated with L-PRF and recombinant human BMP-2. For each patient, surgical sites were evaluated postoperatively at 4 and 16 weeks. Associations between the treatment method and the resolution of MRONJ were analyzed with the adjustment of patient-specific factors that may influence the treatment outcome. At 4 and 16 weeks postoperatively, patients with MRONJ who were treated with both L-PRF and BMP-2 showed favorable outcomes with complete resolution of the lesions, which was statistically significant compared with that of the therapy using L-PRF alone (P = .028). Therefore, the additional use of BMP-2 considerably improved MRONJ healing. Among patient-specific factors, the existence of a bacterial colony in the biopsy specimen was a significant factor that negatively affected disease resolution (P = .017). The combined use of BMP-2 and L-PRF leads to the early resolution of MRONJ; thus patients who need to continue antiresorptive therapy may benefit from the combined regimen. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

[Treatment of cough in respiratory tract infections - the effect of combining the natural active compounds with thymol].

PubMed

Schönknecht, Karina; Krauss, Hanna; Jambor, Jerzy; Fal, Andrzej M

Cough is one of the characteristic symptoms of upper respiratory tract infections (URI). Herbal medicines are often used in the treatment of the cough associated with infection and to accelerate recovery or support the immune system. An example of such products are extracts of thyme and primrose, and also their combination with thymol. Thymus vulgaris is a spasmolytic, antimicrobial, anti-inflammatory, immunomodulatory and antioxidant agent. The most important component responsible for the activity of thyme is thymol contained in the volatile thyme oil. Primrose is, most of all, a saponine agent with expectorant and secretolytic activity, showing also spasmolytic, anti-inflammatory and antimicrobial effects. Because of the additive effects of the mentioned extracts and their wide activity profile they are often used as a combination drug. The use of this combination was assessed in the URI with the effects of alleviation of cough and dyspnea, and shortening the length of the disease. The effectiveness of the drug containing the extracts of thyme and primrose with the addition of thymol (Bronchosol®) was comparable to synthetic ambroxol and its safety has been proved. Moreover, the in-vitro antibacterial and antifungal effects of this drug have been evaluated.

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

Effectiveness of additional supervised exercises compared with conventional treatment alone in patients with acute lateral ankle sprains: systematic review

PubMed Central

van Ochten, John; Luijsterburg, Pim A J; van Middelkoop, Marienke; Koes, Bart W; Bierma-Zeinstra, Sita M A

2010-01-01

Objective To summarise the effectiveness of adding supervised exercises to conventional treatment compared with conventional treatment alone in patients with acute lateral ankle sprains. Design Systematic review. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Cinahl, and reference screening. Study selection Included studies were randomised controlled trials, quasi-randomised controlled trials, or clinical trials. Patients were adolescents or adults with an acute lateral ankle sprain. The treatment options were conventional treatment alone or conventional treatment combined with supervised exercises. Two reviewers independently assessed the risk of bias, and one reviewer extracted data. Because of clinical heterogeneity we analysed the data using a best evidence synthesis. Follow-up was classified as short term (up to two weeks), intermediate (two weeks to three months), and long term (more than three months). Results 11 studies were included. There was limited to moderate evidence to suggest that the addition of supervised exercises to conventional treatment leads to faster and better recovery and a faster return to sport at short term follow-up than conventional treatment alone. In specific populations (athletes, soldiers, and patients with severe injuries) this evidence was restricted to a faster return to work and sport only. There was no strong evidence of effectiveness for any of the outcome measures. Most of the included studies had a high risk of bias, with few having adequate statistical power to detect clinically relevant differences. Conclusion Additional supervised exercises compared with conventional treatment alone have some benefit for recovery and return to sport in patients with ankle sprain, though the evidence is limited or moderate and many studies are subject to bias. PMID:20978065

Continuous and pulsed laser high power beam combiner for additive manufacturing applications

NASA Astrophysics Data System (ADS)

Bassignana, Marta; Califano, Alessio; Pescarmona, Francesco; Braglia, Andrea; Perrone, Guido

2018-02-01

Laser-based additive manufacturing (AM) from metal powders is emerging as the new industrial revolution, although current fabrication approaches still require long mechanical post-processing to improve the final surface quality and meet the design tolerances. To overcome this limitation, the next generation machines are expected to complement laser AM with laser ablation (LA) to implement surface finishing and micro texturing already during the device growth process. With this aim, a new beam combiner to allow the real-time interchange of additive and subtractive processes using the same scanner head has been designed. Extensive tests have been carried out using a 6 kW continuous-wave laser similar to that used for the metal powder fusion and a nanosecond 100W pulsed source similar to that used for laser ablation.

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

Economic evaluation of single-pill combination of indapamide and amlodipine in the treatment of arterial hypertension in the Polish setting.

PubMed

Kawalec, Paweł; Holko, Przemysław; Stawowczyk, Ewa; Borowiec, Łukasz; Filipiak, Krzysztof J

2015-01-01

Arterial hypertension is a common disorder that affects around 9 million adults in Poland. Single-pill combinations (SPCs) for the treatment of arterial hypertension have significant advantages over the free combinations, resulting in lower risk of cardiovascular events and lower consumption of medical resources. The current ESC/ESH 2013 guidelines for the first time recommend treatment with a combination of thiazide-like diuretic with calcium channel blocker. Currently, no such combination is reimbursed from public funds in Poland. To assess the economic value of treatment with SPC of indapamide and amlodipine (Tertens-AM®) for hypertensive patients compared with free combination therapy (FC), in the Polish setting. As there are currently no published data directly estimating the additional effect of using indapamide + amlo-dipine SPC vs. FC, two extreme approaches are presented: with difference in effectiveness due to improved adherence to the treatment estimated from published studies on other molecules used in hypertension such as SPCs and FCs - the base-case approach (1); and assuming no difference of effectiveness or adherence between SPC and FC of indapamide and amlodipine - the conservative approach (2). Modelling was carried out based on the Markov process in lifetime horizon. In the base-case approach, with the difference in effectiveness between SPC and FC, it was assumed that the differences in compliance translate into the differences in systolic blood pressure. Patients' characteristics were correlated with the risk of events associated with cardiovascular disease, based on the prediction algorithms from the Framingham Heart Study. Costs were considered from a National Health Fund (NHF) perspective and NHF and patient's perspective, and therefore direct medical costs were only included. The treatment with SPC of indapamide and amlodipine in place of FC resulted in 7.6 additional days of life in full health and longer overall patient survival by 2

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

PubMed

Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

2016-07-01

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of a treatment strategy combining CCI-779 plus DTIC versus DTIC monotreatment in human melanoma in SCID mice.

PubMed

Thallinger, Christiane; Werzowa, Johannes; Poeppl, Wolfgang; Kovar, Florian M; Pratscher, Barbara; Valent, Peter; Quehenberger, Peter; Joukhadar, Christian

2007-10-01

This study compares the antineoplastic potential of a novel treatment strategy combining cell cycle inhibitor-779 (CCI-779) plus dacarbazine (DTIC) versus DTIC monotreatment, the current chemotherapeutic mainstay in combating metastatic melanoma. A controlled four-group parallel study design comprising 24-40 mice per tumor cell line was used in a severe combined immunodeficiency (SCID)-mouse xenotransplantation model. SCID mice were injected with 518A2, Mel-JUSO, or 607B human melanoma cells. After they developed tumors, mice received daily CCI-779 or solvent over 14 days. From treatment day 4-8 mice were additionally injected with DTIC or saline. Treatment with CCI-779 plus DTIC was superior to single agent DTIC in two out of three cell lines (P<0.05). The tumor weight reduction was 44+/-17 and 61+/-6% compared with DTIC monotreatment in Mel-JUSO and 607B melanomas, respectively (P<0.05). In contrast, in 518A2 xenotransplants, CCI-779 plus DTIC treatment was as effective as DTIC monotreatment. CCI-779 monotherapy exerted no statistically significant antitumor effect. Collectively, these data indicate that CCI-779 has the potential to increase the chemotherapeutic efficacy, as the combination of CCI-779 plus DTIC proved to be more efficacious compared to DTIC monotherapy in two out of three melanoma cell lines in vivo.

Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder

PubMed Central

Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

2011-01-01

Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1−/−) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations—either directly in brain, or systemic alone —in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the “combined” mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders. PMID:21326216

Postinflammatory hyperpigmentation: evolving combination treatment strategies.

PubMed

Taylor, Susan C; Burgess, Cheryl M; Callender, Valerie D; Fu, Jan; Rendon, Marta I; Roberts, Wendy E; Shalita, Alan R

2006-08-01

Postinflammatory hyperpigmentation (PIH) is a common acquired excess of pigment in the epidermal and/or dermal layers of the skin. Lesions persist for extended periods if untreated, thus therapy is warranted. Topical monotherapies include the standard bleaching agent hydroquinone (HQ) as well as retinoids. Recently, several fixed-dose combination products were introduced to the armamentarium: HQ 4%-retinol 0.15% in a microsponge formulation; HQ 4%-retinol 0.3%; mequinol 2%-tretinoin (RA) 0.01%; and fluocinolone acetonide (FA) 0.01%, HQ 4%, and RA 0.05%. Recent findings have suggested that mequinol 2%-RA 0.01% solution is a promising alternative for the treatment of PIH.

Treatment of landfill leachate using ASBR combined with zeolite adsorption technology.

PubMed

Lim, Chi Kim; Seow, Ta Wee; Neoh, Chin Hong; Md Nor, Muhamad Hanif; Ibrahim, Zaharah; Ware, Ismail; Mat Sarip, Siti Hajar

2016-12-01

Sanitary landfilling is the most common way to dispose solid urban waste; however, improper landfill management may pose serious environmental threats through discharge of high strength polluted wastewater also known as leachate. The treatment of landfill leachate to fully reduce the negative impact on the environment, is nowadays a challenge. In this study, an aerobic sequencing batch reactor (ASBR) was proposed for the treatment of locally obtained real landfill leachate with initial ammoniacal nitrogen and chemical oxygen demand (COD) concentration of 1800 and 3200 mg/L, respectively. ASBR could remove 65 % of ammoniacal nitrogen and 30 % of COD during seven days of treatment time. Thereafter, an effective adsorbent, i.e., zeolite was used as a secondary treatment step for polishing the ammoniacal nitrogen and COD content that is present in leachate. The results obtained are promising where the adsorption of leachate by zeolite further enhanced the removal of ammoniacal nitrogen and COD up to 96 and 43 %, respectively. Furthermore, this combined biological-physical treatment system was able to remove heavy metals, i.e. aluminium, vanadium, chromium, magnesium, cuprum and plumbum significantly. These results demonstrate that combined ASBR and zeolite adsorption is a feasible technique for the treatment of landfill leachate, even considering this effluent's high resistance to treatment.

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

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.

Treatment of antibiotic fermentation wastewater by combined polyferric sulfate coagulation, Fenton and sedimentation process.

PubMed

Xing, Zi-Peng; Sun, De-Zhi

2009-09-15

Attempts were made in this study to examine the combined polyferric sulfate (PFS) coagulation, Fenton and sedimentation process for treatment of non-degradable antibiotic fermentation wastewater. The experimental results indicated that 66.6% of color and 72.4% of chemical oxygen demand (COD) were removed under the optimum conditions of PFS dosage 200mg/L and pH 4.0. In addition, optimal parameters of Fenton process were determined to be 150 mg/L of H(2)O(2) dosage, 120 mg/L of FeSO(4) and 1h of reaction time. When Fenton treated effluent was controlled at pH 7.0, the pollutants could be further removed by sedimentation process. The overall color, COD and suspended solids (SS) removal reached 97.3%, 96.9% and 86.7% under selected conditions, respectively. Thus this study might offer an effective way for wastewater treatment of antibiotics manufacturer and pharmaceutical industry.

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.

Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes

PubMed Central

Dardano, Angela; Bianchi, Cristina; Del Prato, Stefano; Miccoli, Roberto

2014-01-01

Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients’ preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal–bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients’ viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. PMID:25143741

Decentralised black water treatment by combined auto-thermal aerobic digestion and ammonia - A pilot study optimising treatment capacity.

PubMed

Nordin, A; Göttert, D; Vinnerås, B

2018-02-01

Partial heating of black water by auto-thermal aerobic digestion was combined with the addition of 1% w/w urea and monitoring of pathogens and indicator organisms over a 21-day period. After initial mixing, the 160 m 3 black water (60 m 3 heated and 100 m 3 non-heated) was left undisturbed. The urea was confirmed to be fully degraded into ammonia (5.1 g N L -1 ) first after 14 days, while the pH stabilised at around 9.2 after one week. The initial temperature of 17 °C fell by 6 °C during the study. E. coli and Salmonella spp., which are sensitive to ammonia, were inactivated during the first few days of the study, despite the urea only being partly hydrolysed. At day 14, f-RNA bacteriophages could also no longer be detected. The more persistent somatic coliphages, Enterococcus spp. and Ascaris eggs, showed significant but slow inactivation. The treatment proved to be efficient with regards to salmonella, which is a target pathogen in the Swedish context, but for parasite egg inactivation a higher temperature was required. The treatment would benefit from more frequent stirring to speed up the hydrolysis of urea and thus improve treatment efficiency. The alternative treatment scheme could increase capacity by 2.4 times, albeit with a 40% higher cost per volume due to the increased use of urea. Copyright © 2017 Elsevier Ltd. 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.

Combination of Foot Stimulation and Tramadol Treatment Reverses Irritation Induced Bladder Overactivity in Cats

PubMed Central

Mally, Abhijith D.; Zhang, Fan; Matsuta, Yosuke; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.; Tai, Changfeng

2013-01-01

Purpose We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. Materials and Methods Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. Results Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. Conclusions This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects. PMID:23088991

A combination of additives can synergically decrease acrylamide content in gingerbread without compromising sensory quality.

PubMed

Komprda, Tomáš; Pridal, Antonin; Mikulíková, Renata; Svoboda, Zdeněk; Cwiková, Olga; Nedomová, Šárka; Sýkora, Vladimír

2017-02-01

The present study tested whether replacement of the leavening agent ammonium carbonate by sodium hydrogen carbonate in combination with calcium cation and acidifying agent will synergically decrease acrylamide (AA) content in gingerbread. The type of leavening agent and the presence of Ca 2+ and citric acid accounted for 33.6%, 13.2% and 53.2% of the explained variability of the AA content, respectively (P < 0.01). The AA content in gingerbread produced with (NH 4 ) 2 CO 3 alone was 186.5 µg kg -1 . Irrespective of other tested additives, NaHCO 3 decreased (P < 0.05) AA content to 42% compared to (NH 4 ) 2 CO 3 . Combination of NaHCO 3 + CaCl 2 + citric acid in dough reduced (P < 0.05) AA content below the limit of detection (25 µg kg -1 ). The AA content in gingerbread (y; µg kg -1 ) decreased with an increasing number of additives used (x) according to the equation y = 158.8 - 47.94x (r 2 = 0.42; P < 0.0001). A comprehensive sensory analysis did not indicate any significant deterioration (P > 0.05) in the organoleptic quality of gingerbread produced using calcium cation and citric acid. The present study demonstrates that the combination of additives NaHCO 3 /Ca 2+ /citric acid synergically decreases AA content in gingerbread without compromising the sensory quality. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Combination therapies - the next logical step for the treatment of synucleinopathies?

PubMed Central

Valera, E.; Masliah, E.

2015-01-01

Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson’s disease (PD), PD dementia (PDD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA), in which the protein alpha-synuclein (α-syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, utilizing strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared to monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches in order to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-syn accumulation and cell-to-cell transfer, such as immunotherapy against α-syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies. PMID:26388203

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.

The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats

PubMed Central

SUN, Xiaolei; Fengbo, LI; Xinlong, MA; Jianxiong, MA; ZHAO, Bin; ZHANG, Yang; Yanjun, LI; Jianwei, LV; MENG, Xinmin

2015-01-01

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID:26260240

Plants with genetically modified events combined by conventional breeding: an assessment of the need for additional regulatory data.

PubMed

Pilacinski, W; Crawford, A; Downey, R; Harvey, B; Huber, S; Hunst, P; Lahman, L K; MacIntosh, S; Pohl, M; Rickard, C; Tagliani, L; Weber, N

2011-01-01

Crop varieties with multiple GM events combined by conventional breeding have become important in global agriculture. The regulatory requirements in different countries for such products vary considerably, placing an additional burden on regulatory agencies in countries where the submission of additional data is required and delaying the introduction of innovative products to meet agricultural needs. The process of conventional plant breeding has predictably provided safe food and feed products both historically and in the modern era of plant breeding. Thus, previously approved GM events that have been combined by conventional plant breeding and contain GM traits that are not likely to interact in a manner affecting safety should be considered to be as safe as their conventional counterparts. Such combined GM event crop varieties should require little, if any, additional regulatory data to meet regulatory requirements. Copyright © 2010 Elsevier Ltd. All rights reserved.

Combining phytoextraction and biochar addition improves soil biochemical properties in a soil contaminated with Cd.

PubMed

Lu, Huanping; Li, Zhian; Fu, Shenglei; Méndez, Ana; Gascó, Gabriel; Paz-Ferreiro, Jorge

2015-01-01

The main goal of phytoremediation is to improve ecosystem functioning. Soil biochemical properties are considered as effective indicators of soil quality and are sensitive to various environmental stresses, including heavy metal contamination. The biochemical response in a soil contaminated with cadmium was tested after several treatments aimed to reduce heavy metal availability including liming, biochar addition and phytoextraction using Amaranthus tricolor L. Two biochars were added to the soil: eucalyptus pyrolysed at 600 °C (EB) and poultry litter at 400 °C (PLB). Two liming treatments were chosen with the aim of bringing soil pH to the same values as in the treatments EB and PLB. The properties studied included soil microbial biomass C, soil respiration and the activities of invertase, β-glucosidase, β-glucosaminidase, urease and phosphomonoesterase. Both phytoremediation and biochar addition improved soil biochemical properties, although results were enzyme specific. For biochar addition these changes were partly, but not exclusively, mediated by alterations in soil pH. A careful choice of biochar must be undertaken to optimize the remediation process from the point of view of metal phytoextraction and soil biological activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin.

PubMed

Kim, Eui Hyun; Lee, Ji-Hyun; Oh, Yoonjee; Koh, Ilkyoo; Shim, Jin-Kyoung; Park, Junseong; Choi, Junjeong; Yun, Mijin; Jeon, Jeong Yong; Huh, Yong Min; Chang, Jong Hee; Kim, Sun Ho; Kim, Kyung-Sup; Cheong, Jae-Ho; Kim, Pilnam; Kang, Seok-Gu

2017-02-01

Deprivation of tumor bioenergetics by inhibition of multiple energy pathways has been suggested as an effective therapeutic approach for various human tumors. However, this idea has not been evaluated in glioblastoma (GBM). We hypothesized that dual inhibition of glycolysis and oxidative phosphorylation could effectively suppress GBM tumorspheres (TS). Effects of 2-deoxyglucose (2DG) and metformin, alone and in combination, on GBM-TS were evaluated. Viability, cellular energy metabolism status, stemness, invasive properties, and GBM-TS transcriptomes were examined. In vivo efficacy was tested in a mouse orthotopic xenograft model. GBM-TS viability was decreased by the combination of 2DG and metformin. ATP assay and PET showed that cellular energy metabolism was also decreased by this combination. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TS were also significantly suppressed by combined treatment with 2DG and metformin. A transcriptome analysis showed that the expression levels of stemness- and epithelial mesenchymal transition-related genes were also significantly downregulated by combination of 2DG and metformin. Combination treatment also prolonged survival of tumor-bearing mice and decreased invasiveness of GBM-TS. The combination of 2DG and metformin effectively decreased the stemness and invasive properties of GBM-TS and showed a potential survival benefit in a mouse orthotopic xenograft model. Our findings suggest that targeting TS-forming cells by this dual inhibition of cellular bioenergetics warrants expedited clinical evaluation for the treatment of GBM. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Uterine Artery Embolization Combined with Local Methotrexate and Systemic Methotrexate for Treatment of Cesarean Scar Pregnancy with Different Ultrasonographic Pattern

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

Lian Fan; Wang Yu, E-mail: wyfishking@hotmail.com; Chen Wei

Purpose: This study was designed to compare the effectiveness of systemic methotrexate (MTX) with uterine artery embolization (UAE) combined with local MTX for the treatment of cesarean scar pregnancy (CSP) with different ultrasonographic pattern, and to indicate the preferable therapy in CSP patients. Methods: The results of 21 CSP cases were reviewed. All subjects were initially administrated with systemic MTX (50 mg/m{sup 2} body surface area). UAE combined with local MTX was added to the patients who had failed systemic MTX. The transvaginal ultrasonography data were retrospectively assessed, and two different ultrasonographic patterns were found: surface implantation and deep implantationmore » of amniotic sac. The management and its effectiveness for patients with the two ultrasonographic patterns were studied retrospectively. Ultrasound scan and serum {beta}-hCG were monitored during follow-up. Data were analyzed with the Student's t test. Results: Nine patients were successfully treated with systemic MTX. The remaining 12 cases were successfully treated with additional UAE combined with local MTX. According to the classification by Vial et al. of CSP on ultrasonography, most surface implanted CSPs (8/11, 72.7%) could be successfully treated with systemic MTX, whereas most deeply implanted CSPs (9/10, 90%) had failed systemic MTX but still could be successfully treated with additional UAE combined with local MTX. All patients recovered without severe side effects. Most patients with a future desire for reproduction achieved subsequent pregnancy. Conclusions: For CSP patients suitable for nonsurgical treatment, UAE combined with local MTX would be the superior option compared with systemic MTX in the cases with deep implantation of amniotic sac.« less

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

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.

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.

Effective swine wastewater treatment by combining microbial fuel cells with flocculation.

PubMed

Ding, Weijun; Cheng, Shaoan; Yu, Liliang; Huang, Haobin

2017-09-01

Microbial fuel cells (MFCs) provide a cost-effective method for treating swine wastewater treatment and simultaneously producing electricity, yet they need to be combined with other wastewater treatment processes to improve the effluent water quality. In this paper, we constructed single-chamber air-cathode MFCs with a compact configuration for nitrogen and COD removal and high electricity production and combined them with a low-cost flocculation process to discharge higher quality wastewater. We show that MFCs could remove ammonia at a rate of 269.2 ± 0.5 g m -3 d -1 (99.1± 0.1% ammonia removal efficiency) with a maximum power density of 37.5 W m -3 and 21.6% of coulombic efficiency at a 40:60 ratio of raw swine wastewater to denitrification effluent of swine wastewater. Up to 82.5 ± 0.5% COD could be removed with MFCs, from 2735 ± 15 mg L -1 to 480 ± 15 mg L -1 , and flocculation further reduced levels to 90 ± 1 mg L -1 for a 96.6 ± 0.2% overall COD removal efficiency of the combination technology. Cost analysis of the combined MFC and flocculation process showed a net economic benefit of $ 0.026 m -3 . In summary, this novel combination wastewater treatment method provides an effective way to treat swine wastewater to low pollutant levels in the effluent at low cost (a net gain). Copyright © 2017 Elsevier Ltd. All rights reserved.

Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation.

PubMed

Zhang, Wei; Tan, Yongsheng; Ma, Heping

2017-11-01

Gastric cancer (GC), one of the types of tumor most prone to malignancy, is characterized by high lethality. Numerous molecular mediators of GC have been identified, including transcription factors, signaling molecules and non-coding RNAs. Recently, inhibition of angiogenesis has emerged as a potential strategy for GC therapy. In the present study, the levels of vascular endothelial growth factor (VEGF), peroxisome proliferator-activated receptor-α (PPARα) and miR-21 in GC patients and individuals without cancer, and the correlation between VEGF and miR-21, and PPARα and miR-21 expression were analyzed. In addition, the GC MKN45 cell line was treated with apatinib (a tyrosine kinase inhibitor) and aspirin (an activator of the transcription factor, PPARα) to investigate the effects of these compounds on tumorigenesis. Furthermore, the present study attempted to elucidate the molecular mechanisms of alteration of GC tumorigenesis by aspirin and apatinib. The results of the current study demonstrated that there was a higher expression of VEGF and miR-21 in GC tissues compared with that in morphologically adjacent normal tissues whereas PPARα expression was decreased. These results were confirmed in vitro , as treatment of MKN45 cells with VEGF resulted in a significant increase in miR-21 expression and a significant reduction in PPARα protein expression. Furthermore, the inhibitory effects of VEGF on PPARα mRNA and protein expression were demonstrated to be mediated by miR-21. Suppression of PPARα protein expression attenuated the inhibitory effects of miR-21 on the level of PPARα mRNA, thereby enhancing tumorigenesis in gastric cancer. Treatment of MKN45 cells with aspirin reduced the levels of phosphorylated AKT by activating PPARα, whereas treatment with apatinib inhibited the phosphorylation of vascular endothelial growth factor receptor 2 and phosphoinositide-3 kinase in MKN45 cells. Finally, treatment of MKN45 cells with apatinib and aspirin suppressed

NPDES Permit for Woodcock Home Addition Wastewater Treatment Facility in Montana

EPA Pesticide Factsheets

Under NPDES permit MT-0030554, the Salish and Kootenai Housing Authority is authorized to discharge from its Woodcock Home Addition Wastewater Treatment Facility in Lake County, Montana, to a swale draining to Middle Crow Creek.

Electron beam combined with hydrothermal treatment for enhancing the enzymatic convertibility of sugarcane bagasse

NASA Astrophysics Data System (ADS)

Duarte, C. L.; Ribeiro, M. A.; Oikawa, H.; Mori, M. N.; Napolitano, C. M.; Galvão, C. A.

2012-08-01

The use of microbial cellulolytic enzymes is the most efficient process to liberate glucose from cellulose in biomass without the formation of fermentation inhibitors. A combination of pretreatment technologies is an alternative way to increase the access of enzymes to cellulose, and consequently, the conversion yield. In this way, the present study reports on the enzymatic hydrolysis of SCB submitted to three kinds of pretreatment: electron beam processing (EBP), and EBP followed by hydrothermal (TH) and diluted acid (AH) treatment. SCB samples were irradiated using a radiation dynamics electron beam accelerator, and then submitted to thermal and acid (0.1% sulfuric acid) hydrolysis for 40 and 60 min at 180 °C. These samples were submitted to enzymatic hydrolysis (EH) using commercial preparations, including Celluclast 1.5 L and beta-glycosidase. The addition of diluted acid improved TH treatment allowing for a shorter application time. EBP with 50 kGy increased the enzymatic hydrolysis yield of cellulose by 20% after TH and 30% after AH.

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.

[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.

Comparison of conventional medicine, TCM treatment, and combination of both conventional medicine and TCM treatment for patients with chronic obstructive pulmonary disease: study protocol of a randomized comparative effectiveness research trial.

PubMed

Li, Jian-Sheng; Xie, Yang; Li, Su-Yun; Yu, Xue-Qing

2014-05-01

beneficial effects in reducing the frequency and duration of acute exacerbations, improving exercise capacity and psychosocial function of COPD patients. In addition, the combination of conventional medicine and TCM treatments may be most suitable for COPD patients with better effectiveness and economic evaluation. ClinicalTrials.gov NCT01836016.

Combined use of local irradiation and corynebacterium parvum in the treatment of the murine line 1 lung carcinoma

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

Ullrich, R.L.; Adams, L.M.

1978-02-01

The effectiveness of Corynebacterium parvum in combination with local irradiation has been examined in the treatment of the murine line 1 lung carcinoma, a highly radioresistant, weakly immunogenic tumor that kills the host by means of metastatic spread. Sixteen-week-old, specific-pathogen-free female BABL/c mice were given 10/sup 6/ tumor cells im into the right thigh. Tumors were irradiated on Day 7 after transplant. Those receiving C. parvum treatment were given 0.1 mg either by the intralesional (il), ip, or iv route on Day 4 after transplant or by the il or ip route on Day 8. An additional group received C.more » parvum ip once a week for 4 weeks beginning on Day 8. The influence of the various treatments on local control and metastasis was assessed. To evaluate further the time course and incidence of metastases, cleared lungs were examined at 21, 28, and 35 days in groups given irradiation combined with C. parvum on day 8. C. parvum was more effective in facilitating local control and inhibiting metastatic spread when given after radiation exposure rather than before.« less

Successful treatment of ovarian cancer with apatinib combined with chemotherapy

PubMed Central

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-01-01

Abstract Rationale: The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. Patients concerns: A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Diagnosis: Ovarian cancer. Interventions: The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand–foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. Outcomes: The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Lessons: Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially

Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone.

PubMed

Jovanovic, Lois; Hassman, David R; Gooch, Brent; Jain, Rajeev; Greco, Susan; Khutoryansky, Naum; Hale, Paula M

2004-02-01

The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.

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

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.

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

The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells.

PubMed

Segovia-Mendoza, Mariana; Díaz, Lorenza; Prado-Garcia, Heriberto; Reginato, Mauricio J; Larrea, Fernando; García-Becerra, Rocío

2017-01-01

In breast cancer the use of small molecule inhibitors of tyrosine kinase activity of the ERBB family members improves survival thus represents a valuable therapeutic strategy. The addition of calcitriol, the most active metabolite of vitamin D, or some of its analogs, to conventional anticancer drugs, including tyrosine kinase inhibitors (TKIs), has shown an increased effect on the inhibition of cancer cell growth. In this work, we have evaluated the effects and the mechanism of action of the combination of calcitriol or its analog EB1089 with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell proliferation in a concentration-dependent manner. Addition of calcitriol or EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth and AKT and MAPK phosphorylation than all compounds alone. The combined treatments incremented also the expression of active caspase 3 and induced cell death in two and three-dimensional cell culture and significantly inhibited anchorage-independent colony formation. Our results suggest that the addition of calcitriol or its analog EB1089 to conventional targeted therapies, including lapatinib or neratinib might be of benefit to patients with breast cancer, particularly those with an EGFR and/or HER2 positive phenotype.

The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells

PubMed Central

Segovia-Mendoza, Mariana; Díaz, Lorenza; Prado-Garcia, Heriberto; Reginato, Mauricio J; Larrea, Fernando; García-Becerra, Rocío

2017-01-01

In breast cancer the use of small molecule inhibitors of tyrosine kinase activity of the ERBB family members improves survival thus represents a valuable therapeutic strategy. The addition of calcitriol, the most active metabolite of vitamin D, or some of its analogs, to conventional anticancer drugs, including tyrosine kinase inhibitors (TKIs), has shown an increased effect on the inhibition of cancer cell growth. In this work, we have evaluated the effects and the mechanism of action of the combination of calcitriol or its analog EB1089 with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell proliferation in a concentration-dependent manner. Addition of calcitriol or EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth and AKT and MAPK phosphorylation than all compounds alone. The combined treatments incremented also the expression of active caspase 3 and induced cell death in two and three-dimensional cell culture and significantly inhibited anchorage-independent colony formation. Our results suggest that the addition of calcitriol or its analog EB1089 to conventional targeted therapies, including lapatinib or neratinib might be of benefit to patients with breast cancer, particularly those with an EGFR and/or HER2 positive phenotype. PMID:28744399

Urinary retention during combined treatment of postpsychotic depression with duloxetine and olanzapine.

PubMed

Englisch, Susanne; Fritzinger, Michael; Zink, Mathias

2008-01-01

Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine, has been approved for the treatment of major depressive episodes and for female stress urinary incontinence. At present, only sparse experiences are available regarding antidepressive treatment in patients with a psychotic lifetime diagnose, whereas this group of patients often suffer from major depressive episodes. Here, we describe the first case of a male patient with postpsychotic depression who developed the severe side effect of urinary retention during antidepressive treatment with duloxetine combined with olanzapine. After remission of his psychotic episode, the patient presented with depressed mood, psychomotor inhibition, sleep disturbance, and suicidal ideas. Without changing the antipsychotic therapy, we implemented duloxetine (60 mg/d) and the patient significantly improved. However, he increasingly suffered from obstructive voiding difficulties and complained about a weak urinary stream and incomplete voiding leading to unacceptable dribbling. The urinary retention disappeared completely within 1 week after discontinuation of duloxetine. We switched to venlafaxine (150 mg/d) and were able to keep the depression in remission. This case report demonstrates for the first time the onset of urinary retention in postpsychotic depression and during combined treatment with duloxetine and olanzapine. We therefore suggest increased attention on voiding function in particular if several pharmacological agents are combined.

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.

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.

Efficacy of a feed-additive antibacterial combination for improving feedlot cattle performance and health.

PubMed Central

Gallo, G F; Berg, J L

1995-01-01

The effectiveness of a feed-additive antimicrobial combination for improving feedlot performance and health was tested using 4325 high-risk feeder calves randomly allocated to a control group or an experimental group. The experimental group received the conventional ration plus a feed additive containing 700 mg per head/day of chlortetracycline and sulfamethazine from arrival at the feedlot to day 56 of the feeding period. The inclusion of the feed additive to the ration significantly improved average daily gain for days 0-28 (P = 0.0163) and 0-56 (P = 0.0001), and the feed conversion for days 0-28 (P = 0.0061) and 0-56 (P = 0.0004). Additionally, the use of the feed additive significantly reduced the rate of bovine respiratory disease morbidity for days 0-28 (P = 0.0014) and 0-56 (P = 0.0001), the rate of relapses and mortality for days 0-56 (P = 0.0151 and P = 0.0209, respectively), and the rate of animals diagnosed with chronic respiratory disease for days 0-28 and 0-56 (P = 0.0009 and P = 0.0002, respectively). Performance and health improvements produced by the use of the feed additive were cost-effective. PMID:7600512

Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates

PubMed Central

Camargos G. V.; Bhattacharya P.; van Lenthe G. H.; Del Bel Cury A. A.; Naert I.; Duyck J.; Vandamme K.

2015-01-01

Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness. PMID:26027958

The Efficacy, Longevity, and Safety of Combined Radiofrequency Treatment and Hyaluronic Acid Filler for Skin Rejuvenation

PubMed Central

Kim, Hyuk; Park, Kui Young; Choi, Sun Young; Koh, Hyun-Ju; Park, Sun-Young; Park, Won-Seok; Bae, Il-Hong

2014-01-01

Background Recent advances in hyaluronic acid (HA) fillers and radiofrequency (RF) devices have been made in the context of skin rejuvenation and cosmetic surgery. Moreover, combination regimens with both techniques are currently being developed. Objective The present study was designed to examine the clinical and histologic effects of a new needle that incorporates an RF device for HA injections. Methods A new intradermal needle RF device (INNOfill; Pacific Pharma, Korea) was assessed in the present study. In the animal arm, procollagen production was measured by using enzyme-linked immunosorbent assay, the filler volume was quantified by incorporating a dye with filler, and the filler distribution was assessed through the changes in tissue structure. In the human arm, the efficacy of the combination regimen was assessed by using the wrinkle severity rating scale (WSRS). Results In the animal study, RF treatment increased procollagen production in a time-dependent fashion. The total volume was significantly increased with the RF treatment when compared with the filler injections alone, and lasted for up to 7 weeks after treatment. Additionally, the filler distribution was reduced in animals treated with RF when compared with the untreated group. In the human study, the nasolabial folds of subjects treated with RF before filler injections exhibited a significantly greater change in the WSRS score from baseline when compared with the nasolabial folds treated with filler injections alone. Conclusion A new device incorporating RF treatment before HA filler injection may represent a biocompatible and long-lasting advance in skin rejuvenation. PMID:25143672

Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

PubMed

Namba, Masashi; Kim, Shokei; Zhan, Yumei; Nakao, Takafumi; Iwao, Hiroshi

2002-05-01

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

Irradiation and additive combinations on the pathogen reduction and quality of poultry meat.

PubMed

Ahn, Dong U; Kim, Il Suk; Lee, Eun Joo

2013-02-01

Reduction of foodborne illnesses and deaths by improving the safety of poultry products is one of the priority areas in the United States, and developing and implementing effective food processing technologies can be very effective to accomplish that goal. Irradiation is an effective processing technology for eliminating pathogens in poultry meat. Addition of antimicrobial agents during processing can be another approach to control pathogens in poultry products. However, the adoption of irradiation technology by the meat industry is limited because of quality and health concerns about irradiated meat products. Irradiation produces a characteristic aroma as well as alters meat flavor and color that significantly affect consumer acceptance. The generation of a pink color in cooked poultry and off-odor in poultry by irradiation is a critical issue because consumers associate the presence of a pink color in cooked poultry breast meat as contaminated or undercooked, and off-odor in raw meat and off-flavor in cooked meat with undesirable chemical reactions. As a result, the meat industry has difficulties in using irradiation to achieve its food safety benefits. Antimicrobials such as sodium lactate, sodium diacetate, and potassium benzoate are extensively used to extend the shelf-life and ensure the safety of meat products. However, the use of these antimicrobial agents alone cannot guarantee the safety of poultry products. It is known that some of the herbs, spices, and antimicrobials commonly used in meat processing can have synergistic effects with irradiation in controlling pathogens in meat. Also, the addition of spices or herbs in irradiated meat improves the quality of irradiated poultry by reducing lipid oxidation and production of off-odor volatiles or masking off-flavor. Therefore, combinations of irradiation with these additives can accomplish better pathogen reduction in meat products than using them alone even at lower levels of antimicrobials/herbs and

Valsartan addition to amlodipine is more effective than losartan addition in hypertensive patients inadequately controlled by amlodipine.

PubMed

Fogari, Roberto; Mugellini, Amedeo; Preti, Paola; Zoppi, Annalisa; Derosa, Giuseppe

2010-03-03

This study evaluated the effects on blood pressure (BP) of valsartan 160 mg or losartan 100 mg addition to amlodipine 5 mg in hypertensive patients. 221 patients with inadequately controlled BP (DBP >or= 90 mmHg) after 4 weeks of treatment with amlodipine 5 mg were randomized to receive losartan/amlodipine combination therapy or valsartan/amlodipine combination therapy for 4 weeks in a cross-over study design. At the end of the wash-out period and of each treatment period, clinic and ambulatory BP measurements were recorded. 166 patients completed the study. Both combination treatments induced a greater ambulatory BP reduction than did monotherapy. However, the further mean reductions in BP versus monotherapy were significantly greater with the valsartan/amlodipine combination (SBP/DBP: -7.9 +/- 3.4/-6.5 +/- 2.6 mmHg for 24-hour, -8.0 +/- 3.4/-6.6 +/- 2.7 mmHg for daytime; -7.7 +/- 3.3/-6.4 +/- 2.7 mmHg for nighttime) than with the losartan/amlodipine combination (SBP/DBP: -5.5 +/- 2.8/-4.2 +/- 2.1 mmHg for 24-hour, -5.7 +/- 2.9/-4.4 +/- 2.2 mmHg for daytime; -4.8 +/- 2.8/-3.7 +/- 2.2 mmHg for nighttime; P < 0.01 vs valsartan/amlodipine). The incidence of adverse events with valsartan/amlodipine (8%) and losartan/amlodipine (9%) was lower than that observed with amlodipine monotherapy (17%; P < 0.05 vs combinations). Valsartan 160 mg plus amlodipine 5 mg produced greater BP reductions than losartan 100 mg plus amlodipine 5 mg.

Combinational light emitting diode-high frequency focused ultrasound treatment for HeLa cell.

PubMed

Choe, Se-Woon; Park, Kitae; Park, Chulwoo; Ryu, Jaemyung; Choi, Hojong

2017-12-01

Light sources such as laser and light emitting diode or ultrasound devices have been widely used for cancer therapy and regenerative medicines, since they are more cost-effective and less harmful than radiation therapy, chemotherapy or magnetic treatment. Compared to laser and low intensity ultrasound techniques, light emitting diode and high frequency focused ultrasound shows enhanced therapeutic effects, especially for small tumors. We propose combinational light emitting diode-high frequency focused ultrasound treatment for human cervical cancer HeLa cells. Individual red, green, and blue light emitting diode light only, high frequency focused ultrasound only, or light emitting diode light combined with high frequency focused ultrasound treatments were applied in order to characterize the responses of HeLa cells. Cell density exposed by blue light emitting diode light combined with high frequency focused ultrasound (2.19 ± 0.58%) was much lower than that of cells exposed by red and green light emitting diode lights (81.71 ± 9.92% and 61.81 ± 4.09%), blue light emitting diode light (11.19 ± 2.51%) or high frequency focused ultrasound only (9.72 ± 1.04%). We believe that the proposed combinational blue light emitting diode-high frequency focused ultrasound treatment could have therapeutic benefits to alleviate cancer cell proliferation.

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 combination drug. Comprehensive treatment of AR that effectively relieves nasal congestion can also improve patient QoL. Administration of the second-generation antihistamine desloratadine in combination with the decongestant pseudoephedrine may be regarded as an efficacious and convenient option for patients with AR who are particularly troubled by nasal congestion.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

PubMed

Abilleira, Sònia; Ribera, Aida; Cardona, Pedro; Rubiera, Marta; López-Cancio, Elena; Amaro, Sergi; Rodríguez-Campello, Ana; Camps-Renom, Pol; Cánovas, David; de Miquel, Maria Angels; Tomasello, Alejandro; Remollo, Sebastian; López-Rueda, Antonio; Vivas, Elio; Perendreu, Joan; Gallofré, Miquel

2017-02-01

Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care. © 2017 American Heart Association, Inc.

Individual and combined in vitro (anti)androgenic effects of certain food additives and cosmetic preservatives.

PubMed

Pop, Anca; Drugan, Tudor; Gutleb, Arno C; Lupu, Diana; Cherfan, Julien; Loghin, Felicia; Kiss, Béla

2016-04-01

The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti-androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha-dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endoscopic Pilonidal Sinus Treatment Combined With Crystalized Phenol Application May Prevent Recurrence.

PubMed

Gecim, Ibrahim Ethem; Goktug, Utku Ufuk; Celasin, Haydar

2017-04-01

No single treatment yet exists for pilonidal disease that has a short healing time, good cosmetic results, and a low rate of recurrence. Phenol crystal application and diathermy ablation through an endoscope have been used for the treatment of pilonidal disease, but this cohort is the first one to combine them. The purpose of this study was to examine the safety, effectiveness, and short- and long-term outcomes of crystalized phenol treatment combined with endoscopic pilonidal sinus treatment for pilonidal disease. This was a prospective cohort study. Procedures were performed in 2 hospitals by the same surgeon between February and July 2014. Twenty-three patients underwent surgical treatment for pilonidal disease. Under local anesthesia and sedation, all of the patients underwent a video-assisted diathermy ablation of the sinus cavity and the application of phenol crystals. Adverse events were recorded as a measure of safety and tolerability. Failure to heal and recurrence rate were documented and evaluated. Patients were discharged on the same day as surgery. There was no or minimal postoperative pain (mean visual analog scale score, 1.40 ± 0.95). Mean operation time was 20.43 ± 6.19 minutes, and the median return-to-work duration was 2.00 days (mean, 3.03 ± 2.95 d). Patients were followed-up for 18 to 24 months (mean, 22.00 ± 1.88 mo). No serious complications or rehospitalization were observed. No primary failure to heal or recurrence was observed. This study did not include a control group with which to compare and consisted of a relatively small number of patients. Crystalized phenol treatment combined with endoscopic pilonidal sinus treatment was safe, tolerable, and achieved fast and durable healing with no recurrence over an average of 22 months of follow-up.

Combination treatment of pediatric coats' disease: a bicenter study in Taiwan.

PubMed

Lin, Chun-Ju; Chen, San-Ni; Hwang, Jiunn-Feng; Yang, Chung-May

2013-01-01

To present the clinical outcome of different combination treatment modalities in pediatric Coats' disease in two Taiwan medical centers. A retrospective review of clinical records was done of pediatric patients with Coats' disease treated at National Taiwan University Hospital and Changhua Christian Hospital. Data regarding the age at the time of diagnosis, initial presentation, methods of treatment, visual and anatomic results, and complications were recorded. Changes in vision and retinal status with the different methods of treatment were specifically evaluated. From 2005 through 2011, 10 eyes of 9 patients were treated under the diagnosis of Coats' disease. The clinical manifestations varied from localized vascular abnormalities with subretinal fluid and hard exudates to extensive detachment with massive exudates and retinal hemorrhage. The main treatment modalities include argon laser photocoagulation, micropulse laser, and cryotherapy. The adjunctive therapies included intravitreal triamcinolone, bevacizumab, and ranibizumab. The mean follow-up was 40.50 ± 20.52 months (range: 14 to 72 months). Best corrected visual acuity at last follow-up was light perception to 1.0 (20/20 Snellen). Anatomic improvement was achieved in 9 eyes (90%). Visual improvement was noted in 7 eyes (70%), visual stabilization in 2 eyes (20%), and visual deterioration in 1 eye (10%). Vitreous fibrosis evolving into tractional retinal detachment occurred in 1 patient receiving cryotherapy combined with intravitreal bevacizumab injections. No enucleation was ultimately necessary. Pediatric Coats' disease varies greatly in severity. Carefully selected treatment modalities can improve most eyes with different conditions. Intravitreal anti-vascular endothelial growth factor agents may act as useful adjuncts to improve anatomic and functional outcome. Cryotherapy combined with the intravitreal bevacizumab injection in severe cases of exudative retinal detachment may carry the risk of

[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.

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.

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

PubMed

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

2002-06-01

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

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.

Combination of fractional QSRL and IPL for melasma treatment in Chinese population.

PubMed

Tong, La-Ga; Wu, Yan; Wang, Bin; Xu, Xue-Gang; Tu, Han-Deng; Chen, Hong-Duo; Li, Yuan-Hong

2017-02-01

Melasma is the most common and distressing pigmentary disorder presenting to dermatology clinics. Various treatment protocols for melasma have been suggested in the previous literature and applied in various clinical settings. However, no satisfactory therapy has been widely accepted. To evaluate the efficiency and safety of a combination treatment with fractional Q-switched ruby laser (QSRL) and intense pulsed light (IPL) for melasma in Chinese population. Fifty-three Chinese melasma patients were enrolled in this study. Each patient underwent 2 courses of treatments at 2-week interval. One course was composed of 3 successive sessions of 694-nm fractional QSRL at intervals of two weeks followed by one IPL. The efficacy was evaluated by non-invasive measurements and subjective assessments. The adverse effects were recorded. Mean melanin index (MI) and erythema index (EI) significantly decreased from 216.1 and 381.8 pre-treatment to 167.8 and 310.3 post-treatment, respectively. Mean melasma area and severity index (MASI) decreased dramatically from 14.66 before treatment to 5.70 after the final treatment. These values remained at low levels at 3-month follow-up. The percentage of patients who achieved moderate or significant improvements was 73.6%. Adverse effects of QSRL and IPL were minimal. The combination treatment of fractional QSRL and IPL would be a promising modality for managing melasma in Chinese patients.

Combined treatment in carcinoma of the nasopharynx

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

Souhami, L.; Rabinowits, M.

1988-08-01

From October 1982 to August 1984, 30 previously untreated patients with biopsy-proven carcinoma of the nasopharynx, stage III (26.5%) and stage IV (73.5%), received combined radiotherapy (6,000 to 7,000 cGy over a period of 7 to 7.5 weeks) and chemotherapy (mitomycin-C 10 mg/M2, IV; 5-fluorouracil 750 mg/M2, IV; and methotrexate 30 mg/M2, IV) concomitantly. There were 20 males and 10 females, with a median age of 40 years. Minimal follow-up duration was 24 months. Actuarial overall survival rate at 48 months was 49%. Complete local response was achieved in 75% of the patients, with 31% of the cases failing distantly.more » The complication rate was high and included severe mucositis, xerostomia, and septicemia (fatal in two cases). Despite high local disease control, survival rate did not increase. A randomized trial is urgently needed to establish whether or not combined treatment is of value in advanced carcinoma of the nasopharynx.« less

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

PubMed

Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

2015-05-15

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

Review on effect of chemical, thermal, additive treatment on mechanical properties of basalt fiber and their composites

NASA Astrophysics Data System (ADS)

Jain, Naman; Singh, Vinay Kumar; Chauhan, Sakshi

2017-12-01

Basalt fiber is emerging out the new reinforcing material for composites. To overcome some of the disadvantages of fibers such as poor bonding to polymers, low thermal stability and high moisture absorption fiber characteristics are modified with chemical, thermal and additive treatments. Chemical treatment corrosive resistance to alkali and acid were investigated which were used to clean and modify the surface of fiber for higher bonding with resins. To improve the thermal stability and reduce moisture uptake thermal treatment such as plasma and non thermal plasma were used which increased the surface roughness and change the chemical composition of surface of basalt fiber. Additive treatment is used to improve the mechanical properties of fibers, in basalt fiber additive treatment was done with SiO2 additive because of its chemical composition which contains major content of SiO2. In present investigation review on the effect of different treatment such as chemical, thermal and additive were studied. Effect of these treatment on chemical composition of the surface of basalt fiber and corrosion to acidic and alkali solution were studied with their effect on mechanical properties of basalt fiber and their composite.

Combined treatment with Dendrobium candidum and black tea extract promotes osteoprotective activity in ovariectomized estrogen deficient rats and osteoclast formation.

PubMed

Wang, Ming-Yue; Shen, Chang; An, Meng-Fei; Xie, Chuan-Qi; Wu, Xin; Zhu, Qiang-Qiang; Sun, Bin; Huang, Yan-Ping; Zhao, Yun-Li; Wang, Xuan-Jun; Sheng, Jun

2018-05-01

Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected. Results showed that OVX rats that were treated orally with a DC and BTE combination for 12 weeks maintained their calcium (Ca) and phosphorus (P) homeostasis and exhibited significantly enhanced estradiol (E 2 ) and OPG levels. This combination treatment also simultaneously reduced levels of interleukin (IL)-1β, IL-6 and improved the organ coefficients of the uterus and femur as well as BMD and BMC in OVX rats. In addition, this DC and BTE combination suppressed osteoclast differentiation in the RANKL-stimulated osteoclastogenesis of RAW 264.7 cells and effectively inhibited the expression of osteoclast-associated genes and proteins. The results of this study further highlight the fact that a combination of DC and BTE improved ovariectomy-induced osteoporosis in rats and suppressed RANKL-stimulated osteoclastogenesis in RAW 264.7 cells. This combination also significantly alleviated osteoporosis when compared to the alternative sole treatments above, due to synergistic effects among components. One partial mechanism of this combination might be the inhibition of osteoclast proliferation and the regulation of NFATC1/c-Fos expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Combined Treatment of Mulberry Leaf and Fruit Extract Ameliorates Obesity-Related Inflammation and Oxidative Stress in High Fat Diet-Induced Obese Mice

PubMed Central

Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook

2013-01-01

Abstract The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity. PMID:23957352

Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice.

PubMed

Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook; Lim, Yunsook

2013-08-01

The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity.

[Synergistic lethal effect of combined treatment of arsenic trioxide and aclacinomycin on human acute myeloid leukemia cell line KG-1a].

PubMed

Ye, Y B; Xu, X J; Chen, Y H; Zhang, M W; Qiu, D F; Guo, Z W; He, H Q

2017-04-23

Objective: To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a. Methods: Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis. Results: The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 μmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 μmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone ( P <0.05). The apoptotic rate of KG-1a cells treated with both 1.5 μmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 μmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone ( P <0.05). The apoptotic rate of KG-1a cells treated with both 3.0 μmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 μmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone ( P <0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents. Conclusions: Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell

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.

Plant tolerance to mercury in a contaminated soil is enhanced by the combined effects of humic matter addition and inoculation with arbuscular mycorrhizal fungi.

PubMed

Cozzolino, V; De Martino, A; Nebbioso, A; Di Meo, V; Salluzzo, A; Piccolo, A

2016-06-01

In a greenhouse pot experiment, lettuce plants (Lactuca sativa L.) were grown in a Hg-contaminated sandy soil with and without inoculation with arbuscular mycorrhizal fungi (AMF) (a commercial inoculum containing infective propagules of Rhizophagus irregularis and Funneliformis mosseae) amended with different rates of a humic acid (0, 1, and 2 g kg(-1) of soil), with the objective of verifying the synergistic effects of the two soil treatments on the Hg tolerance of lettuce plants. Our results indicated that the plant biomass was significantly increased by the combined effect of AMF and humic acid treatments. Addition of humic matter to soil boosted the AMF effect on improving the nutritional plant status, enhancing the pigment content in plant leaves, and inhibiting both Hg uptake and Hg translocation from the roots to the shoots. This was attributed not only to the Hg immobilization by stable complexes with HA and with extraradical mycorrhizal mycelium in soil and root surfaces but also to an improved mineral nutrition promoted by AMF. This work indicates that the combined use of AMF and humic acids may become a useful practice in Hg-contaminated soils to reduce Hg toxicity to crops.

Influence of extracellular polymeric substances (EPS) treated by combined ultrasound pretreatment and chemical re-flocculation on water treatment sludge settling performance.

PubMed

Chen, Wei; Gao, Xiaohong; Xu, Hang; Cai, Yan; Cui, Jianfeng

2017-03-01

Extracellular polymeric substances (EPS) are high molecular weight polymers and play a significant role in floc stability, floc size, bioflocculation and sludge settleability. The destruction and reconstruction of EPS improve the performance of solid-water separation processes. In this study, the influence of combined ultrasound pretreatment and chemical re-flocculation on the spatial distribution and composition of EPS was examined. Settleability efficiency demonstrated that the optimal operating condition was an ultrasound pretreatment time of 15 min at pH 6. Sludge particles were greatly disintegrated and the protein-like substances were converted into smaller molecules after ultrasound treatment, and pH had important effects on solubilization and degradation of protein-like substances. The flocs of sludge water after addition of polyacrylamide were larger in size and denser in structure than those resulting from addition of polyaluminium chloride. However, polyaluminium chloride had a better capacity for degrading EPS, especially at a dosage of 1.2 g/g total suspended solids. The results of this research show that the combination of ultrasonication and chemical re-flocculation is effective in treating sludge water from a drinking water treatment plant. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fixed-functional appliance treatment combined with growth hormone therapy.

PubMed

Jung, Min-Ho

2017-09-01

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

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

PubMed

Fredin, Ken; Lorås, Håvard

2017-10-01

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

[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.

Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.

PubMed

Berhanu, Aklile; Prigge, Jonathan T; Silvera, Peter M; Honeychurch, Kady M; Hruby, Dennis E; Grosenbach, Douglas W

2015-07-01

The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy.

PubMed

Ren, Feifeng; Tang, Lin; Cai, Yin; Yuan, Xin; Huang, Wenhan; Luo, Lei; Zhou, Jun; Zheng, Yaning

2015-05-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin-angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN. Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI + ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI). In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups. Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.

Two-stage combined treatment of acid mine drainage and municipal wastewater.

PubMed

Deng, Dongyang; Lin, Lian-Shin

2013-01-01

This study examined the feasibility of the combined treatment of field-collected acid mine drainages (AMD, pH = 4.2 ± 0.9, iron = 112 ± 118 mg/L, sulfate = 1,846 ± 594 mg/L) and municipal wastewater (MWW, avg. chemical oxygen demand (COD) = 234-333 mg/L) using a two-stage process. The process consisted of batch mixing of the two wastes to condition the mixture solutions, followed by anaerobic biological treatment. The mixings performed under a range of AMD/MWW ratios resulted in phosphate removal of 9 to ∼100%, the mixture pH of 6.2-7.9, and COD/sulfate concentration ratio of 0.05-5.4. The biological treatment consistently removed COD and sulfate by >80% from the mixture solutions for COD/sulfate ratios of 0.6-5.4. Alkalinity was produced in the biological treatment causing increased pH and further removal of metals from the solutions. Scanning electron microscopy of produced sludge with energy dispersion analysis suggested chemical precipitation and associated adsorption and co-precipitation as the mechanisms for metal removal (Fe: >99%, Al: ∼100%, Mn: 75 to ∼100%, Ca: 52-81%, Mg: 13-76%, and Na: 56-76%). The study showed promising results for the treatment method and denoted the potential of developing innovative technologies for combined management of the two wastes in mining regions.

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments.

PubMed

Wallace, David K; Dean, Trevano W; Hartnett, Mary Elizabeth; Kong, Lingkun; Smith, Lois E; Hubbard, G Baker; McGregor, Mary Lou; Jordan, Catherine O; Mantagos, Iason S; Bell, Edward F; Kraker, Raymond T

2018-06-07

Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Masked, multicenter, dose de-escalation study. A total of 61 premature infants with type 1 ROP. If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Combined endodontic-periodontic treatment of a palatal groove: a case report.

PubMed

Schwartz, Scott A; Koch, Michael A; Deas, David E; Powell, Charles A

2006-06-01

The palatal groove is a developmental anomaly that predisposes the tooth involved to a severe periodontal defect. When further complicated by pulp necrosis, these grooves often present a diagnostic and treatment planning challenge that requires an interdisciplinary treatment approach. This case report describes the successful collaborative management of a maxillary lateral incisor with an extensive palatal groove using a combination of nonsurgical endodontic therapy, odontoplasty, and periodontal regenerative techniques.

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

Effects of a combined treatment with GPR30 agonist G-1 and herceptin on growth and gene expression of human breast cancer cell lines.

PubMed

Lubig, Julia; Lattrich, Claus; Springwald, Anette; Häring, Julia; Schüler, Susanne; Ortmann, Olaf; Treeck, Oliver

2012-06-01

Expression of G-protein-coupled receptor 30 (GPR30) is present in HER2-overexpressing breast cancer. In this study, we examined to what extent GPR30-agonist G-1 would affect the antitumoral action of trastuzumab (Herceptin). Combined treatment with both drugs exerted an additive growth-inhibitory effect on breast cancer cells which was accompanied by a significant decline of cyclin A2 expression both on the protein and the mRNA level. Combined treatment also resulted in expression changes of c-fos, cyclin D1, or p21/WAF-1. The results of our study encourage further attempts to test the relevance of these in vitro data in the clinical setting.

Combination Treatment with Apricoxib and IL-27 Enhances Inhibition of Epithelial-Mesenchymal Transition in Human Lung Cancer Cells through a STAT1 Dominant Pathway

PubMed Central

Lee, Mi-Heon; Kachroo, Puja; Pagano, Paul C; Yanagawa, Jane; Wang, Gerald; Walser, Tonya C; Krysan, Kostyantyn; Sharma, Sherven; John, Maie St.; Dubinett, Steven M; Lee, Jay M

2015-01-01

Background The cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many malignancies, including lung cancer. Apricoxib, a selective COX-2 inhibitor, has been described to inhibit epithelial-mesenchymal transition (EMT) in human malignancies. The mechanism by which apricoxib may alter the tumor microenvironment by affecting EMT through other important signaling pathways is poorly defined. IL-27 has been shown to have anti-tumor activity and our recent study showed that IL-27 inhibited EMT through a STAT1 dominant pathway. Objective The purpose of this study is to investigate the role of apricoxib combined with IL-27 in inhibiting lung carcinogenesis by modulation of EMT through STAT signaling. Methods and Results Western blot analysis revealed that IL-27 stimulation of human non-small cell lung cancer (NSCLC) cell lines results in STAT1 and STAT3 activation, decreased Snail protein and mesenchymal markers (N-cadherin and vimentin) and a concomitant increase in expression of epithelial markers (E-cadherin, β-and γ-catenins), and inhibition of cell migration. The combination of apricoxib and IL-27 resulted in augmentation of STAT1 activation. However, IL-27 mediated STAT3 activation was decreased by the addition of apricoxib. STAT1 siRNA was used to determine the involvement of STAT1 pathway in the enhanced inhibition of EMT and cell migration by the combined IL-27 and apricoxib treatment. Pretreatment of cells with STAT1 siRNA inhibited the effect of combined IL-27 and apricoxib in the activation of STAT1 and STAT3. In addition, the augmented expression of epithelial markers, decreased expression mesenchymal markers, and inhibited cell migration by the combination treatment were also inhibited by STAT1 siRNA, suggesting that the STAT1 pathway is important in the enhanced effect from the combination treatment. Conclusion Combined apricoxib and IL-27 has an enhanced effect in inhibition of epithelial-mesenchymal transition and cell

Combination Treatment of Citral Potentiates the Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with Pirarubicin for Colorectal Cancer.

PubMed

Fang, Zhiyuan; Wang, Yu; Li, Hao; Yu, Shuaishuai; Liu, Ziying; Fan, Zhichao; Chen, Xiaomin; Wu, Yuying; Pan, Xuebo; Li, Xiaokun; Wang, Cong

2017-10-02

Citral is a widely used penetration enhancer that has been used to assist the delivery of drugs through the skin. In this study we aimed to investigate the effectiveness of combination treatments of citral with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer and to unravel the underlying mechanism by which citral increased the efficacy of HIPEC. In vitro experiments indicated that citral increased cytoplasmic absorption of pirarubicin and potentiated the effects of pirarubicin on colorectal cancer cells to induce apoptosis. Intracellular reactive oxygen species (ROS) activity was elevated after single or combo treatments with pirarubicin, leading to compromised NF-κB signaling. Therefore, the results suggested that the effects of citral were mediated by increasing cell permeability and ROS productions. Furthermore, the colorectal xenograft model was used to evaluate the efficacy of the combo treatment at the histological and molecular levels, which showed that the cotreatment with citral for colorectal cancer increased the efficacy of HIPEC with pirarubicin with respect to both ascite control and tumor load. The results indicated that citral was an effective additive for HIPEC with pirarubicin for colorectal cancer, which warrant further effort to explore the translational application of this new treatment regimen.

Evaluation of Combined Peracetic acid and UV treatment for ...

EPA Pesticide Factsheets

The current study evaluates the effectiveness of the combined application of Peracetic acid and ultraviolet radiation as alternative disinfectant agents to the traditional chlorination of wastewater effluents. Various pathogens (E. coli, enterococci and fecal coliforms) were evaluated in the study. Four experiments were conducted using low to high PAA levels and UV dosages. E. coli and enterococci were resistant to low to moderate PAA dosage (0.5- 1 mg/L). These microbes can be removed effectively at high PAA dosage (2.5 mg/L) with 30 min contact time. Fecal coliforms were completely inactivated even at a low PAA dose of 0.7 mg/L. E. coli was more susceptible to UV disinfection than enterococci at low UV dosages. Enterococci required at least 40 mJ/cm2 for 2.5 log inactivation. In combined PAA + UV treatment, low UV intensities between 7 – 40 mJ/cm2 showed poor disinfection performance at a low PAA concentration of 1.5 mg/L. High UV intensities of 120 and 60 mJ/cm2 inactivated all the pathogens to below detection levels even at low to moderate PAA (0.7 mg/L and 1 mg/L) pretreatment concentration. Combined PAA + UV treatment at 1 mg/L (for 15 and 30 min contact time) + 120 and 60 mJ/cm2 did not show any regrowth of microbes, whereas PAA only disinfection with 15 min contact time showed regrowth of enterococci and fecal coliforms. UV only disinfection showed E. coli regrowth. • This pilot scale study was designed for providing necessary parameter optimization

Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

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

Hojka-Osinska, Anna, E-mail: hojka@immuno.iitd.pan.wroc.pl; Ziolo, Ewa, E-mail: ziolo@immuno.iitd.pan.wroc.pl; Rapak, Andrzej, E-mail: rapak@immuno.iitd.pan.wroc.pl

Highlights: Black-Right-Pointing-Pointer The combination of fenretinide and indomethacin induces a high level of cell death. Black-Right-Pointing-Pointer Apoptotic pathway is caspase-independent. Black-Right-Pointing-Pointer Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergisticmore » effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.« less

Development of a multi-modal Monte-Carlo radiation treatment planning system combined with PHITS

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

Kumada, Hiroaki; Nakamura, Takemi; Komeda, Masao

A new multi-modal Monte-Carlo radiation treatment planning system is under development at Japan Atomic Energy Agency. This system (developing code: JCDS-FX) builds on fundamental technologies of JCDS. JCDS was developed by JAEA to perform treatment planning of boron neutron capture therapy (BNCT) which is being conducted at JRR-4 in JAEA. JCDS has many advantages based on practical accomplishments for actual clinical trials of BNCT at JRR-4, the advantages have been taken over to JCDS-FX. One of the features of JCDS-FX is that PHITS has been applied to particle transport calculation. PHITS is a multipurpose particle Monte-Carlo transport code, thus applicationmore » of PHITS enables to evaluate doses for not only BNCT but also several radiotherapies like proton therapy. To verify calculation accuracy of JCDS-FX with PHITS for BNCT, treatment planning of an actual BNCT conducted at JRR-4 was performed retrospectively. The verification results demonstrated the new system was applicable to BNCT clinical trials in practical use. In framework of R and D for laser-driven proton therapy, we begin study for application of JCDS-FX combined with PHITS to proton therapy in addition to BNCT. Several features and performances of the new multimodal Monte-Carlo radiotherapy planning system are presented.« less

[Combined treatment of endometriosis: radical yet gentle].

PubMed

Alkatout, Ibrahim; Wedel, Thilo; Maass, Nicolai

2018-02-01

Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the management of individual patients. This should take into account the severity of the disease and whether the patient desires to have children. Particular emphasis is laid on the anatomical intersections which, when injured, can lead to persistent damage of the anterior, middle or posterior compartment and are not infrequently the cause of urological and urogynaecological follow-up measures. Typical symptoms of endometriosis include chronic pelvic pain, subfertility, dysmenorrhoea, deep dyspareunia, cyclical bowel or bladder symptoms (e. g. dyschezia, bloating, constipation, rectal bleeding, diarrhoea and haematuria), abnormal menstrual bleeding, chronic fatigue and low back pain. Approx. 50 % of all female teenagers and up to 32 % of all women of reproductive age who have been operated for chronic pelvic pain or dysmenorrhoea suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 % and > 60 % and is very much dependent on integrated management and surgical skills. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should be reserved to appropriate

Combination of metformin and pioglitazone and its effect in treatment of comorbid pathology.

PubMed

Shaienko, Zlatoslava O; Bobyreva, Lyudmila Ye

2018-01-01

Introduction: The early development and high incidence of cardiovascular lesion in patients with type 2 diabetes mellitus is one of the most serious challenges for the diabetology worldwide. The aim: The purpose of the paper is to determine the dynamics of the insulin resistance indices in patients with type 2 diabetes mellitus concomitant with coronary heart disease in the combination therapy with metformin and pioglitazone during 3 and 6 months. Materials and methods: 95 patients with type 2 diabetes mellitus and coronary heart disease have been treated and randomized into two groups: the comparison group (n=37), treated with metformin and sulfonylureas, and the study group (n=58), treated with metformin in combination with pioglitazone. Prior, after 3 and 6 months of treatment C-peptide was assessed and index of the insulin resistance was calculated. Results: The resulting data proved the statistically significant lowering of the markers and level of the insulin resistance under the effect of combination treatment with metformin and pioglitazone. Conclusions: The proposed variant of the combination therapy has a positive effect on the clinical course of the coronary heart disease in patients with type 2 diabetes mellitus, well tolerated by the patients and can be considered as the pathogenetic factor in the treatment of these diseases.

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…

[Clinical effect of hemoperfusion combined with hemodialysis in treatment of severe organophosphate pesticide poisoning].

PubMed

Guo, Lei; Ye, Hua; Pan, Liwei; Sun, Laifang; Ying, Binyu

2014-12-01

To investigate the clinical effect of hemoperfusion combined with hemodialysis in the treatment of severe organophosphate pesticide poisoning. Ninety-eight patients with severe organophosphate pesticide poisoning who were admitted to the emergency department of our hospital from March 2005 to September 2013 were equally divided into control group and observation group according to treatment methods. The control group was given conventional emergency treatment, while the observation group was given hemoperfusion combined with hemodialysis and the conventional emergency treatment. The clinical outcomes and complications of two groups were compared. In the control group, 35 patients were cured and 14 patients died, so the cure rate was 71.4%. In the treatment group, 46 patients were cured and 3 patients died, so the cure rate was 93.9%. The treatment group had a significantly higher cure rate than the control group (χ² = 8.611, P < 0.05). And the treatment group had significantly shorter duration of coma (P < 0.01), mean length of hospital stay (P < 0.01), and time to recovery of cholinesterase activity (P < 0.01) and a significantly reduced dose of atropine than the control group (P < 0.01). The control group had significantly more cases of urinary retention than the treatment group (18 vs. 6, χ² = 4.991, P < 0.05). And the control group had more cases of intermediate syndrome, respiratory failure, delayed neurological damage, and rebound than the treatment group. Hemoperfusion combined hemodialysis has a good clinical effect and causes fewer complications in treating severe organophosphate pesticide poisoning, so it is worthy of clinical promotion.

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

Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine

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

Mueller, W.U.S.; Streffer, C.; Wurm, R.

1985-01-01

The influence of caffeine (0.1 or 2 mM), X-rays (0.24 Gy or 0.94 Gy, or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X-rays as well as caffeine induced micronuclei. The dose-effect curve after irradiation was linear for the dose range measured. Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation-induced micronuclei was observed when irradiation of themore » embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.« less

Early postoperative magnet application combined with hydrocolloid dressing for the treatment of earlobe keloids.

PubMed

Park, Tae Hwan; Chang, Choong Hyun

2013-04-01

To prevent the recurrence of earlobe keloids after surgical removal, a reliable and safe postoperative treatment method is critical. To the authors' knowledge, no studies have elucidated the most effective postoperative dressing method for preventing the recurrence of earlobe keloids. This study aimed to compare keloid recurrence rates in patients whose keloids were dressed using conventional methods (plain gauze or a polyvinyl alcohol sponge) with those of a matched cohort of patients whose keloids were dressed using magnets combined with hydrocolloid materials. This observational case-control study compared a retrospective cohort of patients whose keloids were dressed using conventional methods with a matched prospective cohort of patients whose keloids were dressed using magnets combined with hydrocolloid materials. The study included patients with pathologically confirmed earlobe keloids that were surgically excised with primary closure. Patients 8 years of age or older underwent adjuvant pressure therapy with magnets at the study hospital. Patients were excluded from the study if they were unavailable for follow-up evaluation, if they had received additional adjuvant therapy during treatment, or if histologic confirmation of a keloid was not obtained. Matched-pair analysis was performed using the McNemar test. Treatment outcome was evaluated as recurrence or nonrecurrence. Overall, 9 (11.2%) of the 80 study patients experienced recurrence. The recurrence rate was significantly lower in the matched case group (2 of 40, 5%) than in the matched control group (7 of 40, 17.5%) during the follow-up period of 18 months (p=0.0253). The authors' novel dressing of magnets and hydrocolloid materials appears to be effective in reducing earlobe keloid recurrence. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to

Tinnitus therapy using tailor-made notched music delivered via a smartphone application and Ginko combined treatment: A pilot study.

PubMed

Kim, So Young; Chang, Mun Young; Hong, Min; Yoo, Sun-Gil; Oh, Dongik; Park, Moo Kyun

2017-10-01

Notched music therapy has been suggested to be effective for relieving tinnitus. We have developed a smartphone application using tailor-made notched music for tinnitus patients. This study aimed to evaluate the effect of this smartphone application on reducing tinnitus. In addition, we investigated the predictive factors for tinnitus treatment outcome using this smartphone application. A total of 26 patients who were chronically distressed by tinnitus with a ≥18 Tinnitus Handicap Inventory (THI) score were recruited from March 2013 to March 2015 (National Clinical Trial (NCT) Identifier Number 01663467). Patients were instructed to listen to tailor-made notched music through our smartphone application for 30-60min per day and were prescribed Ginkgo biloba for 3 months. Treatment outcome was evaluated using the THI, a visual analogue scale that measures the effects of tinnitus in terms of loudness, noticeable time, annoyance, and disruption of daily life. Demographic data, including age, sex, duration of tinnitus, and pre-treatment scores on questionnaires such as the Beck Depression Inventory (BDI), State Trait Anxiety Inventory (TAI), and Pittsburgh Sleep Quality Index (PSQI) scores were compared between the effective and non-effective groups according to the differences between their pre- and post-treatment THI scores. Smartphone application-delivered notched music therapy and Ginko combined treatment improved the THI score from 33.9±18.9 to 23.1±15.2; the effect was particularly marked for the emotional score of the THI. Improvement in the THI score was positively correlated with the initial THI score (P=0.001, adjusted estimated value=0.49, 95% confidence interval=0.25-0.73). Chronic tinnitus patients who underwent smartphone application-delivered notched music therapy and Ginko combined treatment showed improved THI scores, particularly the emotional score of the THI. A smartphone application-delivered therapy and Ginko combined treatment may be more

Decomposition of intact chicken feathers by a thermophile in combination with an acidulocomposting garbage-treatment process.

PubMed

Shigeri, Yasushi; Matsui, Tatsunobu; Watanabe, Kunihiko

2009-11-01

In order to develop a practical method for the decomposition of intact chicken feathers, a moderate thermophile strain, Meiothermus ruber H328, having strong keratinolytic activity, was used in a bio-type garbage-treatment machine working with an acidulocomposting process. The addition of strain H328 cells (15 g) combined with acidulocomposting in the garbage machine resulted in 70% degradation of intact chicken feathers (30 g) within 14 d. This degradation efficiency is comparable to a previous result employing the strain as a single bacterium in flask culture, and it indicates that strain H328 can promote intact feather degradation activity in a garbage machine currently on the market.

[Clinical effect of triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori infection in children].

PubMed

Zhao, Hong-Mei; Ou-Yang, Hong-Juan; Duan, Bo-Ping; Xu, Bin; Chen, Zhi-Yong; Tang, Juan; You, Jie-Yu

2014-03-01

To evaluate the clinical effect of proton pump inhibitor-based triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori (Hp) infection among children in terms of Hp eradication rate and incidence of adverse events. A prospective randomised controlled study was conducted on 240 children with a confirmed diagnosis of Hp infection. These patients were randomized into triple therapy (n=120) and probiotics groups (n=120). The triple therapy group received amoxicillin [40 mg/(kg·d), Tid], clarithromycin [15 mg/(kg·d), Bid] and omeprazole [0.7-0.8 mg/(kg·d), Qd], while the probiotics group received Saccharomyces boulardii (250 mg, Bid) in addition to triple therapy. The course of treatment was 14 days in both groups. The adverse events in subjects were recorded by their parents during treatment. Hp eradiation was evaluated by (13)C breath test at 4 weeks after treatment, and the eradication rate and incidence of adverse events were compared between the two groups. The Hp eradication rates were 75.8% (91/120) in the triple therapy group and 85% (102/120) in the probiotics group (P>0.05). Compared with the triple therapy group, the probiotics group had nonsignificantly lower incidence of nausea, vomiting, and abdominal pain (P>0.05) and significantly lower incidence of stomatitis, constipation and diarrhea (P<0.05). Triple therapy combined with Saccharomyces boulardii cannot significantly increase Hp eradication rate, but can significantly reduce the incidence of stomatitis, constipation, and diarrhea during treatment.

Treatment strategies for combining immunostimulatory oncolytic virus therapeutics with dendritic cell injections.

PubMed

Wares, Joanna R; Crivelli, Joseph J; Yun, Chae-Ok; Choi, Il-Kyu; Gevertz, Jana L; Kim, Peter S

2015-12-01

Oncolytic viruses (OVs) are used to treat cancer, as they selectively replicate inside of and lyse tumor cells. The efficacy of this process is limited and new OVs are being designed to mediate tumor cell release of cytokines and co-stimulatory molecules, which attract cytotoxic T cells to target tumor cells, thus increasing the tumor-killing effects of OVs. To further promote treatment efficacy, OVs can be combined with other treatments, such as was done by Huang et al., who showed that combining OV injections with dendritic cell (DC) injections was a more effective treatment than either treatment alone. To further investigate this combination, we built a mathematical model consisting of a system of ordinary differential equations and fit the model to the hierarchical data provided from Huang et al. We used the model to determine the effect of varying doses of OV and DC injections and to test alternative treatment strategies. We found that the DC dose given in Huang et al. was near a bifurcation point and that a slightly larger dose could cause complete eradication of the tumor. Further, the model results suggest that it is more effective to treat a tumor with immunostimulatory oncolytic viruses first and then follow-up with a sequence of DCs than to alternate OV and DC injections. This protocol, which was not considered in the experiments of Huang et al., allows the infection to initially thrive before the immune response is enhanced. Taken together, our work shows how the ordering, temporal spacing, and dosage of OV and DC can be chosen to maximize efficacy and to potentially eliminate tumors altogether.

Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee

PubMed Central

Zeng, Chao; Wei, Jie; Li, Hui; Wang, Yi-lun; Xie, Dong-xing; Yang, Tuo; Gao, Shu-guang; Li, Yu-sheng; Luo, Wei; Lei, Guang-hua

2015-01-01

This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA. PMID:26576862

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

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.

Novel diode-based laser system for combined transcutaneous monitoring and computer-controlled intermittent treatment of jaundiced neonates

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; El-Ahl, Mohammad H. S.; Hamza, Ahmad M.

2001-06-01

The high efficacy of laser phototherapy combined with transcutaneous monitoring of serum bilirubin provides optimum safety for jaundiced infants from the risk of bilirubin encephalopathy. In this paper the authors introduce the design and operating principles of a new laser system that can provide simultaneous monitoring and treatment of several jaundiced babies at one time. The new system incorporates diode-based laser sources oscillating at selected wavelengths to achieve both transcutaneous differential absorption measurements of bilirubin concentration in addition to the computer controlled intermittent laser therapy through a network of optical fibers. The detailed description and operating characteristics of this system are presented.

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

Vegephy: impact of vegetable oils used as extemporaneous additives on pesticide residues and their crop protection potential.

PubMed

Rousseau, G; Coutanceau, P; Lebeau, F; Pigeon, O; Ducat, N; De Vos, P

2013-01-01

Within the framework of the VEGEPHY project set up to assess the effect of refined oils used as extemporaneous additives, both alone and in combination with oligosaccharides (guar, xanthan and carboxymethyl cellulose), on the quality of plant protection treatments for wheat, a study was conducted on the effect of combinations of additives on the level of pesticide residues in wheat plants and grain and their impact on treatment efficiency. The use of some of these additives gave efficiency results that were comparable with those obtained with additives that are currently used but are not bio-based. The use of refined oils as extemporaneous additives, both alone and combined with oligosaccharides, led to better penetration by the pesticide as well as longer persistence of its activity. The experiments were conducted with fungicides, herbicides, plant growth regulators and various types of formulation (EC, SC and WG). The results obtained were conclusive, but they did depend on the physico-chemical properties of the active substance. The risk of exceeding the maximum residue levels (MRLs) of pesticides was also evaluated. Even where the MRLs had not been not exceeded, the experiments showed that in some cases the treatment with these additives could lead to pesticide residues up to two times higher than those measured for the treatment without additives. It would be necessary, therefore, to reduce the treatment dose associated with the additive and/or have a long enough pre-harvest interval to avoid exceeding the MRLs. The use of green additives could be a useful and easy way to attain the European Union (EU) goal of reducing pesticide use by improving the retention of active substances on the plant and reducing the number of treatments.

[Treatment results for different categories of vaginal intraepithelial neoplasia with electrocoagulation, 5-fluorouracil and combined treatment].

PubMed

Veloz-Martínez, María Guadalupe; Quintana-Romero, Verónica; Contreras-Morales, María del Rosario Sandra; Jiménez-Vieyra, Carlos Ramón

2015-10-01

Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer. To compare the results of the treatment for the different categories of VAIN with electrocoagulation, 5-fluorouracil and combined treatment. Observational an analytical study. We stablished groups according to the category of VAIN evaluating and comparing remission, persistence, recurrence, or progression of the disease ac- cording to the received treatment, with a 1-year follow up. The results were compared by chi2 and Kruskal Wallis. The statistics analysis was done with the SPSS program version 20. One hundred thirty seven patients between 20 and 81 years of age (mean age: 52.49 years) were included. Seventy-four percent of the patients had a history of premalignant or malignant cervical lesions. Seventy-four patients had VAIN I, 34 patients had VAIN II, 22 patients had VAIN III and there were seven cases of vaginal carcinoma in situ. Fifty-eight patients were treated with electrocoagulation, 55 patients were treated with 5-FU, 16 patients had combined treatment, and eight patients received expectant management. Sixty three percent of patients had total remission of the lesion, 34% had persistence and 3% showed progression, and there were no cases of recurrence. Results were better in patients with VAIN I treated with 5-FU (bigger percentage of remission P .026), for the remaining categories of VAIN, no treatment showed superior results. The superior response occurs in patients with VAIN I treated with 5-FU. None of the treatments achieves a 100% remission. The VAIN frequency is high, patients with a history of malignant or premalignant cervical pathology should undergo a closer surveillance through cytocolposcopic control with respect to the remaining population.

Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors.

PubMed

Livnat, Tami; Budnik, Ivan; Levy-Mendelovich, Sarina; Avishai, Einat; Misgav, Mudi; Barg, Assaf Arie; Lubetsky, Aharon; Brutman-Barazani, Tami; Kenet, Gili

2017-07-01

Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors. Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII+FEIBA as IV bolus doses. TG spiking studies showed individual responses not correlated to inhibitor titer. Combinations of agents augmented TG as compared to any single agent, while combined FVIII+FEIBA yielded the highest TG, supporting it as a potential treatment. Following emergent successful surgery of child treated by concomitant FVIII+FEIBA, a total of 396 episodes in 7/15 patients were treated with concomitant FVIII+FEIBA. Five patients were treated for bleeding episodes only, whereas 2 were children undergoing immune tolerance induction (ITI) with FEIBA prophylaxis. Four minor surgeries were performed on FVIII+FEIBA repeated infusions. Neither thrombosis nor any other adverse events were documented. A combination of FVIII+FEIBA may be effective and safe as an alternative treatment option for some high-responding inhibitor patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Sintering and properties of Si3N4 with and without additives by HIP treatment

NASA Technical Reports Server (NTRS)

Kuratani, S.; Shimada, M.; Koizumi, M.

1986-01-01

Hot Isostatic Pressing (HIP) of Si3N4 powders with and without additives was performed using a glass container, and various kinds of pressureless-sintered Si3N4 were HIP'ed without a container. The effects of HIP treatment on density, microstructure, flexural strength, microhardness, and fracture toughness on Si3N4 ceramics were studied. Using a glass container it was difficult to reach theoretical density. The microhardness of HIP'ed Si3N4 without additives was low, and the fracture toughness of HIP'ed Si3N4 with and without additives was 22 to 25 W/m-K, and it decreased with increasing the amount of additives. The density and flexural strength, and hardness of pressureless-sintered Si3N4 which contained Al2O and Y2O3 as oxide additives were remarkably improved by HIP treatment using nitrogen as a pressure transmitting gas. It is very important to select the sintering conditions for fabricating the presintered body of Si3N4 in order to improve the mechanical properties of Si3N4 by HIP treatment.

[Rasagiline in daily clinical use. Results of a treatment study of Parkinson patients with a combination treatment].

PubMed

Jost, W H; Klasser, M; Reichmann, H

2008-10-01

Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of monoamine oxidase type B of the second generation. Rasagiline is indicated for the treatment of Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. The efficacy and tolerability of rasagiline has been demonstrated in large-scale, controlled clinical studies in patients with early PD as well as with more advanced PD. This multicentred post-marketing observational study included an investigation of the efficacy and tolerability of rasagiline in a large patient population under conditions of the daily routine in neurologic practice with a special attention on the collection of data regarding a patients' subjective evaluation of quality of life. A total of 754 patients with Parkinson's disease were enrolled, 545 of the patients (63% male patients, mean age 68 years, mean duration of PD 6 years, Hoehn & Yahr stage II to III in 69% of the patients) started rasagiline 1 mg/day as adjunct therapy for up to 4 months. The PD symptoms were rated by the physicians using the Columbia University Rating Scale (CURS) and the clinical fluctuations subscale of the Unified Parkinson's Disease Rating Scale (UPDRS, part IV B). Different aspects of quality of life were rated by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39). In addition, patients documented the number of hours spend in the OFF-state in "24-hour" home diaries prior to each of the assessment visits. During the treatment period rasagiline was most frequently co-administered with levodopa/DCI (81.7%) and/or dopamine agonists (65.8%). The mean treatment duration was 117.4 (+/-36.4) days, during which PD medication remained unchanged in 86.6% of the cases. The improvement rates in each of the CURS items ranged between 31.1% to 48.4% and the total score was reduced by 22% under the therapy of rasagiline. In the motor part (tremor

Treatment of Combined Spinal Deformity in Patient with Ollier Disease and Abnormal Vertebrae

PubMed Central

Ryabykh, S. О.; Gubin, A. V.; Prudnikova, О. G.; Kobyzev, А. Е.

2012-01-01

We report staged treatment of severe combined spinal deformity in an 11-year-old patient with Ollier disease and abnormal cervical vertebra. Combined scoliosis with systemic pathology and abnormal vertebrae is a rare condition and features atypical deformity location and rapid progression rate and frequently involves the rib cage and pelvis, disturbing the function of chest organs and skeleton. Progressive deformity resulted in cachexia and acute respiratory failure. A halo-pelvic distraction device assembled of Ilizarov components was employed for a staged surgical treatment performed for lifesaving indications. After vital functions stabilized, the scoliosis curve of the cervical spine was corrected and fixed with a hybrid system of transpedicular supporting points, connecting rods, and connectors that provided staged distraction during growth. The treatment showed good functional and cosmetic result. PMID:24436859

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

PubMed

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-11-15

The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

Degradation of triclosan and its main intermediates during the combined irradiation and biological treatment.

PubMed

Wang, Shizong; Wang, Jianlong

2018-05-01

Triclosan is an extensively applied antimicrobial agent which has been frequently detected in the environment. In this paper, the degradation of triclosan and its main intermediates was investigated during the combined irradiation and biological treatment. The results showed that triclosan degradation increased with increase of absorbed dose, the removal efficiency of triclosan was 62%, 77%, 87%, 91% and 94%, respectively at 1, 2, 3, 4 and 5 kGy. The final removal efficiency of triclosan after the combined irradiation and biological process was 81%, 86%, 90%, 92% and 95%, respectively. During the irradiation process, two main intermediates, that is, 4,4'-2'-phenoxyphenol (Intermediate 1) and 4-chloro-2'-phenoxyphenol (Intermediate 2) were detected, in which Intermediate 1 dominated during the irradiation process. In the following biological treatment process, Intermediates 1 and 2 could be further degraded. In single biological treatment process, the final removal efficiency of triclosan was 54%, and Intermediates 1 and 2 were detected. Intermediate 1 could be biodegraded while Intermediate 2 could not. The concentration of Intermediate 2 increased during biological treatment process. In conclusion, irradiation as pre-treatment process can enhance the degradation of triclosan and improve the biodegradability of Intermediate 2. Combined irradiation and biological process can be promising for treating antibiotic-containing wastewater.

Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride

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

Rabin, B.M.; Hunt, W.A.; Lee, J.

1987-08-01

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride didmore » produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.« less

Sulphaphenazole, streptomycin and sulphaphenazole combination, trimethoprim, and erythromycin in the treatment of chancroid.

PubMed Central

Kumar, B; Sharma, V K; Bakaya, V

1990-01-01

One hundred and thirty six patients with chancroid were treated with four different treatment regimens; (A) Sulphaphenazole 1 g 12 hourly by mouth x 10 days (B) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days; (C) trimethoprim 200 mg 12 hourly by mouth x 7-10 days, and (D) erythromycin 500 mg 6 hourly orally x 7-10 days. Cure rates of 9% with sulphaphenazole alone, 48% with streptomycin and sulphaphenazole combination, 93% with trimethoprim and 100% with erythromycin were obtained. Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid. There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology. Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out. PMID:2187791

Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1987-08-01

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.

Stem cells and combination therapy for the treatment of traumatic brain injury.

PubMed

Dekmak, AmiraSan; Mantash, Sarah; Shaito, Abdullah; Toutonji, Amer; Ramadan, Naify; Ghazale, Hussein; Kassem, Nouhad; Darwish, Hala; Zibara, Kazem

2018-03-15

TBI is a nondegenerative, noncongenital insult to the brain from an external mechanical force; for instance a violent blow in a car accident. It is a complex injury with a broad spectrum of symptoms and has become a major cause of death and disability in addition to being a burden on public health and societies worldwide. As such, finding a therapy for TBI has become a major health concern for many countries, which has led to the emergence of many monotherapies that have shown promising effects in animal models of TBI, but have not yet proven any significant efficacy in clinical trials. In this paper, we will review existing and novel TBI treatment options. We will first shed light on the complex pathophysiology and molecular mechanisms of this disorder, understanding of which is a necessity for launching any treatment option. We will then review most of the currently available treatments for TBI including the recent approaches in the field of stem cell therapy as an optimal solution to treat TBI. Therapy using endogenous stem cells will be reviewed, followed by therapies utilizing exogenous stem cells from embryonic, induced pluripotent, mesenchymal, and neural origin. Combination therapy is also discussed as an emergent novel approach to treat TBI. Two approaches are highlighted, an approach concerning growth factors and another using ROCK inhibitors. These approaches are highlighted with regard to their benefits in minimizing the outcomes of TBI. Finally, we focus on the consequent improvements in motor and cognitive functions after stem cell therapy. Overall, this review will cover existing treatment options and recent advancements in TBI therapy, with a focus on the potential application of these strategies as a solution to improve the functional outcomes of TBI. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Investigation of a combined platinum and electron lifetime control treatment for silicon

NASA Astrophysics Data System (ADS)

Jia, Yunpeng; Cui, Zhihang; Yang, Fei; Zhao, Bao; Zou, Shikai; Liang, Yongsheng

2017-02-01

In silicon, the effect of Combined Lifetime Treatment (CLT) involving platinum diffusion and subsequent electron irradiation is different from the separate treatments of platinum diffusion and electron irradiation, even the treatment of electron irradiation followed by platinum diffusion. In this paper, we investigated the experimental behavior of different kinds of lifetime treated samples. We found that the reverse leakage current (Irr) increases with the increasing platinum diffusion temperature or electron irradiation dose in the separate treatments. Conversely, Irr of the CLT samples decreased with rising platinum diffusion temperature at the same dose of subsequent electron irradiation. By deep-level transient spectroscopy (DLTS), a new energy level E7 (Ec -0.376 eV) was found in our CLT samples. The new level E7 suppresses the dominance of the deeper level E8 (Ec -0.476 eV), which is caused by electron irradiation directly and results in Irr's increase. The formation of the level E7 comes from the complex defect-combined effect between platinum atoms and silicon vacancies, and it affects device's characteristics finally. These research will be helpful to the development of platinum-diffused devices used in intense electron irradiation environments.

COMBINE genetics study: the pharmacogenetics of alcoholism treatment response: genes and mechanisms.

PubMed

Goldman, David; Oroszi, Gabor; O'Malley, Stephanie; Anton, Raymond

2005-07-01

Partial efficacy of treatment and differences in adverse events across individuals are a challenge and an opportunity in the treatment of alcoholism. Individuation of therapy and understanding origins of differential treatment response may require identification of inherited functional variants of genes. The neurobiology of reward, executive cognitive function, anxiety and dysphoria have been identified as critical domains that may have a genetic basis that could predict treatment response. The COMBINE Study presents a unique opportunity to evaluate specific genetic loci (markers) that affect neurobiology central to addiction and extended withdrawal. The study also addresses variation in drug metabolism and action. Candidate genetic markers are selected for study based on functionality and abundance. COMT Vall58Met is a common (minor allele frequency 0.42), functional, catecholamine-metabolizing enzyme polymorphism with threefold relevance. Vall58Met alters executive cognitive function, stress and anxiety responses and brain endogenous opioid function. OPRM1 Asn40Asp is a common (minor allele frequency 0.10), functional polymorphism of the mu-opioid receptor, which may serve as a gatekeeper molecule in naltrexone's actions and was recently reported to affect naltrexone response. HTTLPR (minor allele frequency 0.40) alters serotonin transporter function to affect anxiety, dysphoria and obsessional behavior, which are assessed in COMBINE and may be related to relapse and addictive behavior. All genetic testing is consented through a separate human research protocol, and the testing is conducted nonclinically, confidentially and apart from the clinical record to protect human research participants who have volunteered for this aspect of COMBINE.

The combined effects of vinclozolin and procymidone do not deviate from expected additivity in vitro and in vivo.

PubMed

Nellemann, Christine; Dalgaard, Majken; Lam, Henrik Rye; Vinggaard, Anne Marie

2003-02-01

The combination effects of the well-known antiandrogenic fungicides, vinclozolin and procymidone, were tested both in vitro and in vivo. In vitro both vinclozolin and procymidone significantly inhibited the binding of agonist to the androgen receptor with the concentration that resulted in 50% inhibition (IC(50)) values of 0.1 and 0.6 micro M, respectively. By applying the isobole method, the effect of combining the two pesticides in vitro was found to be additive. In castrated testosterone-treated rats the administration of vinclozolin starting at 10 mg/kg led to a decrease in organ weight of all tested reproductive organs. The levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were increased significantly with doses of 100 mg/kg vinclozolin and above. Expression of the androgen-responsive gene, TRPM-2, was increased starting at 100 mg/kg vinclozolin. For procymidone, reproductive organ weights were diminished at 10 mg/kg and LH was increased at a concentration of 25 mg/kg and above, compared to the testosterone-treated controls. FSH was significantly increased only at 25 mg/kg procymidone. The studied gene expressions were changed by 100 mg/kg procymidone. Dosing the animals with a combination of a 1:1 mixture of vinclozolin and procymidone resulted in a weight reduction in the reproductive organs and an increase of serum LH and FSH as early as with 10 mg/kg combined dose. The relative expressions of TRPM-2 and PBP C3 were changed compared to controls at 100 mg/kg. The level of 5-HT in the rat brain was increased after a dose of 10 mg/kg. Using the isobole method, comparisons of the observed and predicted effects assuming additivity on reproductive organ weights, hormone levels, and gene expression showed agreement and thus the combination effects are suggested to be additive in vivo as well as in vitro.

[Efficiency of combined methods of hemorroid treatment using hal-rar and laser destruction].

PubMed

Rodoman, G V; Kornev, L V; Shalaeva, T I; Malushenko, R N

2017-01-01

To develop the combined method of treatment of hemorrhoids with arterial ligation under Doppler control and laser destruction of internal and external hemorrhoids. The study included 100 patients with chronic hemorrhoids stage II and III. Combined method of HAL-laser was used in study group, HAL RAR-technique in control group 1 and closed hemorrhoidectomy with linear stapler in control group 2. Сomparative evaluation of results in both groups was performed. Combined method overcomes the drawbacks of traditional surgical treatment and limitations in external components elimination which are inherent for HAL-RAR. Moreover, it has a higher efficiency in treating of hemorrhoids stage II-III compared with HAL-RAR and is equally safe and well tolerable for patients. This method does not increase the risk of recurrence, reduces incidence of complications and time of disability.

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.

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

Augmented growth inhibition of B16-BL6 melanoma by combined treatment with a selective matrix metalloproteinase inhibitor, MMI-166, and cytotoxic agents.

PubMed

Hojo, Kanji; Maki, Hideo; Sawada, Takuko Yamada; Maekawa, Ryuji; Yoshioka, Takayuki

2002-01-01

MMI-166 is a selective matrix metalloproteinase (MMP) inhibitor. The purpose of this study was to evaluate the antitumor efficacy of the combined treatment of MMI-166 with paclitaxel or carboplatin. Mice bearing B16-BL6 melanoma were treated p.o. with MMI-166 from 1 day after tumor inoculation. The mice were administered i.v. with either paclitaxel or carboplatin at the maximum tolerated dose (MTD). MMI-166 monotherapy inhibited in vivo growth of the B16-BL6 tumor to an extent similar to that of paclitaxel or carboplatin monotherapy. When MMI-166 was combined with paclitaxel or carboplatin, the antitumor efficacy was significantly (p < 0.01) augmented in comparison with either MMI-166 or each cytotoxic agent alone. The hematotoxicity study demonstrated that daily treatment with MMI-166 did not affect the blood cell number in the mice and more importantly the combination of MMI-166 with paclitaxel did not augment the hematotoxicity caused by paclitaxel. An in vitro cytotoxicity study showed that MMI-166 itself has neither direct cytotoxicity against B16-BL6 tumor cells nor does it augment the cytotoxicity of paclitaxel or carboplatin. These results indicate that augmented antitumor activity of the combination treatment was not simply due to the augmentation of direct cytotoxic activity, but was rather an additive effect of the antitumor activities of different mechanisms. They suggest the effectiveness of a combination therapy of MMI-166 with paclitaxel or carboplatin in clinical therapy.

An observational study of patient satisfaction with fesoterodine in the treatment of overactive bladder: effects of additional educational material.

PubMed

Schneider, T; Arumi, D; Crook, T J; Sun, F; Michel, M C

2014-09-01

To compare the effects of additional educational material on treatment satisfaction of overactive bladder (OAB) patients treated with a muscarinic receptor antagonist. In an observational study of OAB patients being treated by their physician with fesoterodine for 4 months (FAKTEN study), sites were randomised to providing standard treatment or additional educational material including the SAGA tool. Patient satisfaction was assessed by three validated patient-reported outcomes including the Treatment Satisfaction Question. Because of premature discontinuation of the study, descriptive statistical analysis was performed. A total of 431 and 342 patients received standard treatment or additional educational material, respectively. At study end, 76.1% [95% CI = 71.3, 80.4] of patients with standard care and 79.6% [95% CI = 74.4, 84.1] with additional SAGA tool were satisfied with treatment (primary end-point). Comparable outcomes with and without the additional educational material were also found in various patient subgroups, at the 1-month time point, and for the other patient-reported outcomes. A notable exception was the subgroup of treatment-naïve patients in which the percentage of satisfied patients was 77.2% vs. 89.5% with standard treatment and additional SAGA tool, respectively (post hoc analysis). In an observational study, most overactive bladder patients were satisfied with fesoterodine treatment. Because of the small sample size, the study does not support or refute the hypothesis that adding the SAGA tool will improve patient satisfaction with treatment. The potential effect of additional educational material in treatment-naïve patients warrants further dedicated studies. © 2014 John Wiley & Sons Ltd.

Pharmacological treatment of obstructive sleep apnea with a combination of pseudoephedrine and domperidone.

PubMed

Larrain, Augusto; Kapur, Vishesh K; Gooley, Ted A; Pope, Charles E

2010-04-15

To determine the effect of the drug combination domperidone and pseudoephedrine on nocturnal oximetry measurements and daytime sleepiness in patients with obstructive sleep apnea. We recruited patients with severe snoring and apneic episodes willing to undergo repeated nocturnal oximetry testing. Following baseline clinical history, Epworth Sleepiness Scale administration, and home overnight nocturnal oximetry, patients were started on weight-adjusted doses of domperidone and pseudoephedrine. Follow-up oximetry studies were performed at the patient's convenience. On the final visit, a repeat clinical history, Epworth score, and oximetry were obtained. Seventeen of 23 patients noted disappearance of snoring and apneic episodes. Another 2 patients reported improvement in snoring and no apneic episodes. All but one patient had a decrease in Epworth scores (mean decrease 9.4 (95% CI, 6.8-12.1, p < 0.0001). Mean oxygen saturation (2.5; 95% Cl, 0.66-4.41, p = 0.008), percent time with oxygen saturation < 90% (14.8; 95% CI, 24.4 to 5.2, p = 0.003), and the 4% oxygen desaturation index (18.2; 95% CI, 27.3 to 9.1, p < 0.0001) improved significantly. No adverse effects of treatment were noted. The combination of domperidone and pseudoephedrine improved self reported snoring and sleepiness, and may have improved apneic episodes and sleep-related nocturnal oxygen desaturation in patients with obstructive sleep apnea provided the proportion of time spent asleep did not diminish. This drug combination warrants further study as a treatment for obstructive sleep apnea. Obstructive sleep apnea; oximetry; sleepiness; domperidone; pseudoephedrine; pharmacotherapy; desaturation; treatment Larrain A; Kapur VK; Gooley TA; Pope CE. Pharmacological treatment of obstructive sleep apnea with a combination of pseudoephedrine and domperidone.

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.

Rifampicin-containing antibiotic combinations in the treatment of difficult infections.

PubMed

Grüneberg, R N; Emmerson, A M; Ridgway, G L

1984-06-01

Combination of rifampicin with trimethoprim, erythromycin, tetracycline or fusidic acid have some desirable features in the treatment of difficult infections. They are active against a very wide range of possible pathogens. Resistance to rifampicin is rare. Such combinations may be bactericidal and may be usefully synergistic. They may prevent or delay the emergence of bacterial resistant seen when some single agents are used. They can be used in patients with penicillin hypersensitivity. A series of life-threatening infections has been treated with rifampicin-containing combinations. The infections included endocarditis, meningitis, pneumonia, Legionnaire's disease, and head and neck sepsis. A major reason for the choice of drug was often penicillin hypersensitivity. A second reason was the presumption (mostly subsequently confirmed) that streptococci and/or staphylococci were implicated. The clinical outcome of these infections was generally satisfactory, with few side effects and little evidence of the emergence of antibiotic resistance.

Censored data treatment using additional information in intelligent medical systems

NASA Astrophysics Data System (ADS)

Zenkova, Z. N.

2015-11-01

Statistical procedures are a very important and significant part of modern intelligent medical systems. They are used for proceeding, mining and analysis of different types of the data about patients and their diseases; help to make various decisions, regarding the diagnosis, treatment, medication or surgery, etc. In many cases the data can be censored or incomplete. It is a well-known fact that censorship considerably reduces the efficiency of statistical procedures. In this paper the author makes a brief review of the approaches which allow improvement of the procedures using additional information, and describes a modified estimation of an unknown cumulative distribution function involving additional information about a quantile which is known exactly. The additional information is used by applying a projection of a classical estimator to a set of estimators with certain properties. The Kaplan-Meier estimator is considered as an estimator of the unknown cumulative distribution function, the properties of the modified estimator are investigated for a case of a single right censorship by means of simulations.

Identifying the mechanism of Escherichia coli O157:H7 survival by the addition of salt in the treatment with organic acids.

PubMed

Bae, Y-M; Yoon, J-H; Kim, J-Y; Lee, S-Y

2018-01-01

In this study, the effects of the addition of salt to treatment with acids (one of several organic acids and salt in various solutions including rich or minimal broth, buffer, or distilled water) on the reduction of Escherichia coli O157:H7 were investigated. The protein expression profiles corresponding to acid stress (acetic acid) with or without salt addition were studied using a comparative proteomic analysis of E. coli O157:H7. When acetic, lactic, or propionic acid was combined with 3% NaCl, mutually antagonistic effects of acid and salt on viability of E. coli O157:H7 were observed only in tryptone and yeast extract broth. After exposure to acetic acid alone or in combination with salt, approximately 851 and 916 protein spots were detected, respectively. Analysis of 10 statistically significant differentially expressed proteins revealed that these proteins are mainly related to energy metabolism. When we compared protein expression of E. coli O157:H7 treated with acetic acid and the combination of the acid and salt, the differentially expressed proteins were not related to acid stress- and salt stress-inducible proteins such as stress shock proteins. According to these results, the increased resistance of E. coli O157:H7 to acetic acid after the addition of salt may not be the result of synthesis of proteins related to these phenomena; therefore, further research needs to be conducted to identify the mechanism of the mutually antagonistic effect of some organic acids and salt. © 2017 The Society for Applied Microbiology.

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.

New combination treatments in the management of asthma: focus on fluticasone/vilanterol

PubMed Central

Tan, Laren D; Chan, Andrew L; Albertson, Timothy E

2014-01-01

Despite the 2007 National Asthma Education and Prevention Program Expert Panel 3 guidelines for the treatment of uncontrolled asthma, many patients with poorly controlled asthma still continue to tax the health care system. Controlling asthma symptoms and preventing acute exacerbations have been the foundation of care. Using long-term controller treatments such as inhaled corticosteroids (ICS) and inhaled long-acting beta2-agonists (LABAs) is a common approach. While patient responses to recommended pharmacotherapy may vary, poor adherence to therapy also contributes to poor asthma control. A once-daily combination inhaler, such as fluticasone furoate, an ICS, in combination with vilanterol, a LABA, offers increased convenience and potential improved adherence, which should result in enhanced clinical outcomes and reduced exacerbations. The ICS/LABA combination inhaler of fluticasone furoate and vilanterol is currently approved in the United States for use in the maintenance of chronic obstructive pulmonary disease and to reduce exacerbations. This paper reviews the expanding literature on the efficacy of fluticasone furoate and vilanterol in treating asthma. PMID:24833910

Effect of Combined Treatment with AT1 Receptor Antagonists and Tiagabine on Seizures, Memory and Motor Coordination in Mice.

PubMed

Łukawski, Krzysztof; Janowska, Agnieszka; Czuczwar, Stanisław J

2015-01-01

Losartan and telmisartan, angiotensin AT1 receptor antagonists, are widely used antihypertensive drugs in patients. It is also known that arterial hypertension is often present in people with epilepsy, therefore, drug interactions between AT1 receptor antagonists and antiepileptic drugs can occur in clinical practice. The aim of the current study was to assess the effect of losartan and telmisartan on the anticonvulsant activity of tiagabine, a second-generation antiepileptic drug, in mice. Additionally, the effect of the combined treatment with AT1 receptor antagonists and TGB on long-term memory and motor coordination has been assessed in animals. The study was performed on male Swiss mice. Convulsions were examined in the maximal electroshock seizure threshold test. Long-term memory was measured in the passive-avoidance task and motor coordination was evaluated in the chimney test. AT1 receptor antagonists and TGB were administered intraperitoneally. Losartan (50 mg/kg) or telmisartan (30 mg/kg) did not influence the anticonvulsant activity of TGB applied at doses of 2, 4 and 6 mg/kg. However, both AT1 receptor antagonists in combinations with TGB (6 mg/kg) impaired motor coordination in the chimney test. The concomitant treatment of the drugs did not decrease retention in the passive avoidance task. It is suggested that losartan and telmisartan should not affect the anticonvulsant action of TGB in people with epilepsy. Because the combined treatment with AT1 receptor antagonists and TGB led to neurotoxic effects in animals, caution is advised during concomitant use of these drugs in patients.

Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment

PubMed Central

Zhang, Che; Huang, Li; Gu, Jiaowei

2015-01-01

Background. Cerebral palsy (CP) is the most common cause leading to childhood disability. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transplantation is a promising alternative considering the safety and efficacy in current reports. This report represents a case of hUCB-MSCs transplantation combined with basic rehabilitation treatment beginning as early as age 6 months with follow-up as long as 5 years. Methods. A 6-year-old female patient was diagnosed with CP at age 6 months. The patient accepted 4 infusions of intravenous hUCB-MSCs in each course and received 4 courses of transplantation totally. A series of assessments were performed before the first transplantation, including laboratory tests, CDCC Infant Mental Development Scale, and Gross Motor Function Measure-88 (GMFM-88). Then annual assessments using the GMFM-88, Ashworth spasm assessment, and comprehensive function assessment scale were made in addition to the annual laboratory tests. In addition, electroencephalography and brain magnetic resonance imaging were conducted before transplantation and in the follow-up phase. Rehabilitation and safety follow-up have been ongoing for 5 years up to date. Results. There was no complaint about adverse effects during hospitalization or postoperative follow-up. Motor function recovered to normal level according to the evaluation of scales. Language function improved significantly. Linguistic rehabilitation therapy was enhanced for further improvement. Conclusions. The clinical application of hUC-MSCs combined with basic rehabilitation treatment was effective and safe for improving motor and comprehensive function in a patient with CP. PMID:27335947

Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment.

PubMed

Pensel, Patricia E; Elissondo, Natalia; Gambino, Guillermo; Gamboa, Gabriela Ullio; Benoit, J P; Elissondo, María C

2017-10-15

Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments

Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion.

PubMed

Kang, Joon Hee; Lee, Seon-Hyeong; Lee, Jae-Seon; Nam, Boas; Seong, Tae Wha; Son, Jaekyoung; Jang, Hyonchol; Hong, Kyeong Man; Lee, Cheolju; Kim, Soo-Youl

2016-08-02

Among ALDH isoforms, ALDH1L1 in the folate pathway showed highly increased expression in non-small-cell lung cancer cells (NSCLC). Based on the basic mechanism of ALDH converting aldehyde to carboxylic acid with by-product NADH, we suggested that ALDH1L1 may contribute to ATP production using NADH through oxidative phosphorylation. ALDH1L1 knockdown reduced ATP production by up to 60% concomitantly with decrease of NADH in NSCLC. ALDH inhibitor, gossypol, also reduced ATP production in a dose dependent manner together with decrease of NADH level in NSCLC. A combination treatment of gossypol with phenformin, mitochondrial complex I inhibitor, synergized ATP depletion, which efficiently induced cell death. Pre-clinical xenograft model using human NSCLC demonstrated a remarkable therapeutic response to the combined treatment of gossypol and phenformin.

Short-term clinical outcome of orthosis alone vs combination of orthosis, nerve, and tendon gliding exercises and ultrasound therapy for treatment of carpal tunnel syndrome.

PubMed

Sim, Sze En; Gunasagaran, Jayaletchumi; Goh, Khean-Jin; Ahmad, Tunku Sara

2018-02-07

Prospective randomized study. Carpal tunnel syndrome (CTS) has been described as the most common compression neuropathy. Many modalities exist for conservative treatment. Efficacy of each modality has been described in the literature. However, the effectiveness of combination of these modalities is not well established. The purpose of this study is to assess the short-term clinical outcome of conservative treatment for CTS comparing orthosis alone with combination of orthosis, nerve/tendon gliding exercises, and ultrasound therapy. Forty-one patients who presented to Upper Limb Reconstructive and Microsurgery Clinic, University Malaya Medical Centre with CTS and positive electrodiagnostic study were recruited. Fifteen patients had bilateral CTS. Fifty-six wrists were equally randomized to orthosis alone and a combined therapy of orthosis, nerve/tendon gliding exercise, and ultrasound therapy. All patients were required to complete the Boston Carpal Tunnel Questionnaire during the first visit and 2 months after treatment. Both the orthosis and combined therapy groups showed a significant improvement in symptoms and function after treatment. The mean difference of symptoms in the orthosis group was 0.53; 95% confidence interval [CI]: 0.23-0.83 (P = .001) and in the combined therapy group was 0.48; 95% CI: 0.24-0.72 (P < .001). Mean difference of function in the orthosis group was 0.59; 95% CI: 0.28-0.91 (P = .001) and combined group was 0.69; 95% CI: 0.49-0.89 (P < .001). However, there was no significant difference in symptom severity and functional status scores between the groups. Our findings support other findings where orthosis and exercises improved symptom severity and functional status scores, however, there was no significant difference between orthosis alone and combined treatment. Patients who underwent conservative management for CTS showed improvement in symptoms and function. However, the combination of orthosis, nerve/tendon gliding exercises

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

PubMed Central

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

Stabilization of lead in incineration fly ash by moderate thermal treatment with sodium hydroxide addition

PubMed Central

Yang, Yuanyi; He, Yong; Sun, Xiaolong; Ge, Li-Ya; Zhang, Kewei; Yang, Weizhong

2017-01-01

Municipal solid waste (MSW) incineration fly ash (IFA) can be potentially reused as a substitute for some raw materials, but treatment for detoxification is indispensable owing to high contents of heavy metals in fly ash. In the present work, due to excessive leaching concentration of lead (Pb), a moderate thermal treatment with sodium hydroxide (NaOH) addition was employed to stabilize Pb in IFA. The moderate thermal treatment was performed under relatively low temperature ranging from 300 to 500°C and at retention time from 1 to 3 h with NaOH addition in a range of 1 to 9%. Leaching results showed that leaching concentrations of Pb in IFA leachates decreased below the standard for hazardous waste identification (5 mg/L) in China under all treatment scenarios. With the increase of temperature, retention time and the amount of NaOH, the concentration of Pb were further suppressed in IFA leachates. Especially, at 500°C for 3 h with 9% NaOH addition, the concentration of Pb dropped to 0.18 mg/L, which was below the standard for sanitary landfill (0.25 mg/L) in China. In thermal process, needle-like crystallites melted to form granules and clumps with compacter structure and less pores. After the thermal treatment, water-soluble and exchangeable fractions of Pb significantly decreased. Therefore, the thermal treatment coupled with NaOH could be applied to realize the environmentally sound management of MSW IFA. PMID:28586368

Stabilization of lead in incineration fly ash by moderate thermal treatment with sodium hydroxide addition.

PubMed

Gong, Bing; Deng, Yi; Yang, Yuanyi; He, Yong; Sun, Xiaolong; Ge, Li-Ya; Zhang, Kewei; Yang, Weizhong

2017-01-01

Municipal solid waste (MSW) incineration fly ash (IFA) can be potentially reused as a substitute for some raw materials, but treatment for detoxification is indispensable owing to high contents of heavy metals in fly ash. In the present work, due to excessive leaching concentration of lead (Pb), a moderate thermal treatment with sodium hydroxide (NaOH) addition was employed to stabilize Pb in IFA. The moderate thermal treatment was performed under relatively low temperature ranging from 300 to 500°C and at retention time from 1 to 3 h with NaOH addition in a range of 1 to 9%. Leaching results showed that leaching concentrations of Pb in IFA leachates decreased below the standard for hazardous waste identification (5 mg/L) in China under all treatment scenarios. With the increase of temperature, retention time and the amount of NaOH, the concentration of Pb were further suppressed in IFA leachates. Especially, at 500°C for 3 h with 9% NaOH addition, the concentration of Pb dropped to 0.18 mg/L, which was below the standard for sanitary landfill (0.25 mg/L) in China. In thermal process, needle-like crystallites melted to form granules and clumps with compacter structure and less pores. After the thermal treatment, water-soluble and exchangeable fractions of Pb significantly decreased. Therefore, the thermal treatment coupled with NaOH could be applied to realize the environmentally sound management of MSW IFA.

The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.

PubMed Central

Blomberg, B.; Spinaci, S.; Fourie, B.; Laing, R.

2001-01-01

There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs). PMID:11217670

Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

PubMed

Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

2017-03-05

Clopidogrel (Plavix ® , Sanofi-Aventis), the adenosine diphosphate P2Y 12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl 3 -induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel. Copyright © 2017 Elsevier B.V. All rights reserved.

[Clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia].

PubMed

Chen, Qi-Fen; Zhang, Yi-Wei

2018-02-01

To investigate the clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia. A total of 88 children with diarrhea secondary to Mycoplasma pneumoniae pneumonia between June 2015 and March 2017 were divided into control group and study group using a random number table, with 44 children in each group. The children in the control group were given routine treatment combined with azithromycin sequential therapy, and those in the study group were given oral Saccharomyces boulardii powder in addition to the treatment in the control group until the end of azithromycin sequential therapy. After the treatment ended, the two groups were compared in terms of time to improvement of clinical symptoms, length of hospital stay, clinical outcome, defecation frequency before and after treatment, condition of intestinal dysbacteriosis, and incidence of adverse events. Compared with the control group, the study group had significantly shorter time to improvement of clinical symptoms and length of hospital stay (P<0.05). The study group had a significantly higher response rate than the control group (P<0.05). On days 3 and 5 of treatment, the study group had a significant reduction in defecation frequency compared with the control group (P<0.05). The study group had a significantly lower rate of intestinal dysbacteriosis than the control group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). In the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia, Saccharomyces boulardii powder combined with azithromycin sequential therapy can improve clinical symptoms, shorten the length of hospital stay, reduce defecation frequency and the incidence of intestinal dysbacteriosis, and improve clinical outcomes, and does not increase the risk of adverse events.

Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis.

PubMed

Kuehr, Joachim; Brauburger, Jens; Zielen, Stefan; Schauer, Uwe; Kamin, Wolfgang; Von Berg, Andrea; Leupold, Wolfgang; Bergmann, Karl-Christian; Rolinck-Werninghaus, Claudia; Gräve, Michael; Hultsch, Thomas; Wahn, Ulrich

2002-02-01

Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE antibody have complementary modes of action. The purpose of this study was to determine whether combined therapy could provide better efficacy than either treatment alone. We conducted a randomized, double-blinded trial to assess the efficacy and safety of subcutaneously administered anti-IgE (omalizumab) or placebo in children and adolescents with seasonal allergic rhinitis in both a birch pollen season and a grass pollen season (sequential seasons together lasting an average of 84 days). There were 4 treatment arms. Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was started before and maintained during the anticipated pollen seasons (a total of 24 weeks). The primary efficacy variable was symptom load, the sum of daily symptom severity score plus rescue medication use. A total of 221 subjects (intent-to-treat population) aged 6 to 17 years were analyzed for efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by 48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups receiving unrelated SIT were considered placebo controls. In the grass season, symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 (-32%); SIT-grass + anti-IgE, 0.26 (-71%). Anti-IgE therapy conferred a protective effect independent of the type of allergen. Additional clinical benefit was demonstrated in both pollen seasons, whether there was coverage by SIT or not. This combination might prove useful for the treatment of allergic rhinitis, particularly for polysensitized patients.

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.

A Movable Combined Water Treatment Facility for Rainwater Harvesting

NASA Astrophysics Data System (ADS)

Zhang, L.; Liao, L.

2003-12-01

Alarming water shortage and increased water scarcity world wide has led to increased interests in alternative water sources. Rainwater harvesting is one of them which is getting more and more attention. There is a huge potential for generalization and extension of rainwater harvesting system as an alternative water supply. This is especially important for arid and semi-arid regions where the water shortage blocks further social, economical development. Earlier laboratory experiments and field study showed that harvested rainwater requires treatments of different degrees in order to meet the WHO drinking water standards. The main focus of this study is to ascertain the quality of stored rainwater for drinking purposes with emphasis on water disinfection and pollutants removal. A movable, low-cost, fully functional small scale treatment facility is proposed and tested under simulated field condition. A number of actual and potential hazardous pollutants were identified in the collected water samples together with laboratory test. The corresponding water purification procedure and fresh-keeping methods are discussed. The final proposal of this movable facility needs to be further examined to achieve optimal combined treatment efficiency.

Combining Pharmacological and Psychological Treatments for Binge Eating Disorder: Current Status, Limitations, and Future Directions.

PubMed

Grilo, Carlos M; Reas, Deborah L; Mitchell, James E

2016-06-01

Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed.

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

Clinical and radiographic evaluation of intrabony periodontal defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute.

PubMed

Pietruska, Małgorzata; Skurska, Anna; Pietruski, Jan; Dolińska, Ewa; Arweiler, Nicole; Milewski, Robert; Duraj, Ewa; Sculean, Anton

2012-11-01

The aim of this study has been to compare the clinical and radiographic outcome of periodontal intrabony defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute application. Thirty patients diagnosed with advanced periodontits were divided into two groups: the control group (OFD), in which an open flap debridement procedure was performed and the test group (OFD+NHA), in which defects were additionally filled with nanocrystalline hydroxyapatite bone substitute material. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR) and clinical attachment level (CAL) were measured prior to, then 6 and 12months following treatment. Radiographic depth and width of defects were also evaluated. There were no differences in any clinical and radiographic parameters between the examined groups prior to treatment. After treatment, BOP, GI, PD, CAL, radiographic depth and width parameter values improved statistically significantly in both groups. The PI value did not change, but the GR value increased significantly after treatment. There were no statistical differences in evaluated parameters between OFD and OFD+NHA groups 6 and 12months after treatment. Within the limits of the study, it can be concluded that the additional use of nanocrystalline hydroxyapatite bone substitute material after open flap procedure does not improve clinical and radiographic treatment outcome. Copyright © 2012 Elsevier GmbH. All rights reserved.

Improving 4D plan quality for PBS-based liver tumour treatments by combining online image guided beam gating with rescanning

NASA Astrophysics Data System (ADS)

Zhang, Ye; Knopf, Antje-Christin; Weber, Damien Charles; Lomax, Antony John

2015-10-01

Pencil beam scanned (PBS) proton therapy has many advantages over conventional radiotherapy, but its effectiveness for treating mobile tumours remains questionable. Gating dose delivery to the breathing pattern is a well-developed method in conventional radiotherapy for mitigating tumour-motion, but its clinical efficiency for PBS proton therapy is not yet well documented. In this study, the dosimetric benefits and the treatment efficiency of beam gating for PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data sets, which give realistic 4DCT extracting motion information from 4DMRI. The value of 4DCT(MRI) is its capability of providing not only patient geometries and deformable breathing characteristics, but also includes variations in the breathing patterns between breathing cycles. In order to monitor target motion and derive a gating signal, we simulate time-resolved beams’ eye view (BEV) x-ray images as an online motion surrogate. 4DDCs have been performed using three amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived from either pre-implanted fiducial markers or the diaphragm. In addition, gating has also been simulated in combination with up to 19 times rescanning using either volumetric or layered approaches. The quality of the resulting 4DDC plans has been quantified in terms of the plan homogeneity index (HI), total treatment time and duty cycle. Results show that neither beam gating nor rescanning alone can fully retrieve the plan homogeneity of the static reference plan. Especially for variable breathing patterns, reductions of the effective duty cycle to as low as 10% have been observed with the smallest gating rescanning window (3 mm), implying that gating on its own for such cases would result in much longer treatment times. In addition, when rescanning is applied on its own, large differences between volumetric

[Combined treatment course at a health resort of patients with chronic erosive gastritis].

PubMed

Mezhueva, P F; Novozhilova, L I

1989-01-01

Multiple modality treatment of erosive gastritis (100 cases) in Essentuki spa combined oral intake of mineral water (spring N 4) with carbon dioxide baths and pelotherapy. Therapeutic effect was achieved in all the patients: the erosions disappeared in 49% and reduced in 51% of those treated. The conclusion is made on effectiveness of such combined therapy in chronic erosive gastritis.

Apicidin and Docetaxel Combination Treatment Drives CTCFL Expression and HMGB1 Release Acting as Potential Antitumor Immune Response Inducers in Metastatic Breast Cancer Cells12

PubMed Central

Buoncervello, Maria; Borghi, Paola; Romagnoli, Giulia; Spadaro, Francesca; Belardelli, Filippo; Toschi, Elena; Gabriele, Lucia

2012-01-01

Currently approved combination regimens available for the treatment of metastatic tumors, such as breast cancer, have been shown to increase response rates, often at the cost of a substantial increase in toxicity. An ideal combination strategy may consist of agents with different mechanisms of action leading to complementary antitumor activities and safety profiles. In the present study, we investigated the effects of the epigenetic modulator apicidin in combination with the cytotoxic agent docetaxel in tumor breast cell lines characterized by different grades of invasiveness. We report that combined treatment of apicidin and docetaxel, at low toxicity doses, stimulates in metastatic breast cancer cells the expression of CTCF-like protein and other cancer antigens, thus potentially favoring an antitumor immune response. In addition, apicidin and docetaxel co-treatment specifically stimulates apoptosis, characterized by an increased Bax/Bcl-2 ratio and caspase-8 activation. Importantly, following combined exposure to these agents, metastatic cells were also found to induce signals of immunogenic apoptosis such as cell surface expression of calreticulin and release of considerable amounts of high-mobility group box 1 protein, thus potentially promoting the translation of induced cell death into antitumor immune response. Altogether, our results indicate that the combined use of apicidin and docetaxel, at a low toxicity profile, may represent a potential innovative strategy able to activate complementary antitumor pathways in metastatic breast cancer cells, associated with a potential control of metastatic growth and possible induction of antitumor immunity. PMID:23019417

New environmentally-benign concepts in wood protection: the combination of organic biocides and non-biocidal additives

Treesearch

Frederick Green; Tor P. Schultz

2003-01-01

The principal wood preservative for residential use is currently a broad-spectrum biocide which contains As, Cr and Cu. However, the use of totally organic wood preservative systems in certain applications or localities may be required in the future. This will greatly increase the price of treated wood. The combination of organic biocides with non-biocidal additives to...

Combining medically assisted treatment and Twelve-Step programming: a perspective and review.

PubMed

Galanter, Marc

2018-01-01

People with severe substance use disorders require long-term rehabilitative care after the initial treatment. There is, however, a deficit in the availability of such care. This may be due both to inadequate medical coverage and insufficient use of community-based Twelve-Step programs in many treatment facilities. In order to address this deficit, rehabilitative care for severe substance use disorders could be promoted through collaboration between practitioners of medically assisted treatment, employing medications, and Twelve-Step-oriented practitioners. To describe the limitations and benefits in applying biomedical approaches and Twelve-Step resources in the rehabilitation of persons with severe substance use disorders; and to assess how the two approaches can be employed together to improve clinical outcome. Empirical literature focusing on clinical and manpower issues is reviewed with regard (a) to limitations in available treatment options in ambulatory and residential addiction treatment facilities for persons with severe substance use disorders, (b) problems of long-term rehabilitation particular to opioid-dependent persons, associated with the limitations of pharmacologic approaches, (c) the relative effectiveness of biomedical and Twelve-Step approaches in the clinical context, and (d) the potential for enhanced use of these approaches, singly and in combination, to address perceived deficits. The biomedical and Twelve-Step-oriented approaches are based on differing theoretical and empirically grounded models. Research-based opportunities are reviewed for improving addiction rehabilitation resources with enhanced collaboration between practitioners of these two potentially complementary practice models. This can involve medications for both acute and chronic treatment for substances for which such medications are available, and Twelve-Step-based support for abstinence and long-term rehabilitation. Clinical and Scientific Significance: Criteria for

Efficient reduction of pathogenic and spoilage microorganisms from apple cider by combining microfiltration with UV treatment.

PubMed

Zhao, Dongjun; Barrientos, Jessie Usaga; Wang, Qing; Markland, Sarah M; Churey, John J; Padilla-Zakour, Olga I; Worobo, Randy W; Kniel, Kalmia E; Moraru, Carmen I

2015-04-01

Thermal pasteurization can achieve the U. S. Food and Drug Administration-required 5-log reduction of pathogenic Escherichia coli O157:H7 and Cryptosporidium parvum in apple juice and cider, but it can also negatively affect the nutritional and organoleptic properties of the treated products. In addition, thermal pasteurization is only marginally effective against the acidophilic, thermophilic, and spore-forming bacteria Alicyclobacillus spp., which is known to cause off-flavors in juice products. In this study, the efficiency of a combined microfiltration (MF) and UV process as a nonthermal treatment for the reduction of pathogenic and nonpathogenic E. coli, C. parvum, and Alicyclobacillus acidoterrestris from apple cider was investigated. MF was used to physically remove suspended solids and microorganisms from apple cider, thus enhancing the effectiveness of UV and allowing a lower UV dose to be used. MF, with ceramic membranes (pore sizes, 0.8 and 1.4 μm), was performed at a temperature of 10 °C and a transmembrane pressure of 155 kPa. The subsequent UV treatment was conducted using at a low UV dose of 1.75 mJ/cm(2). The combined MF and UV achieved more than a 5-log reduction of E. coli, C. parvum, and A. acidoterrestris. MF with the 0.8-μm pore size performed better than the 1.4-μm pore size on removal of E. coli and A. acidoterrestris. The developed nonthermal hurdle treatment has the potential to significantly reduce pathogens, as well as spores, yeasts, molds, and protozoa in apple cider, and thus help juice processors improve the safety and quality of their products.

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

PubMed Central

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

2009-01-01

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

Treatment of condyloma acuminata in pregnant women with cryotherapy combined with proanthocyanidins: Outcome and safety

PubMed Central

YANG, LI-JUAN; ZHU, DONG-NING; DANG, YAN-LING; ZHAO, XIONG

2016-01-01

Patients with condyloma acuminata (CA) during pregnancy represent a special risk group. The outcomes of many treatment methods for such cases are not satisfactory. The purpose of the present study was to evaluate the treatment outcome and safety of cryotherapy combined with proanthocyanidins (PCs) for CA in pregnant women. In this study, 46 pregnant women with CA were treated with cryotherapy combined with PCs. The lesions were sprayed with liquid nitrogen until the color of the wart changed from flesh colored to purple. A PC-containing formulation was then sprayed onto a non-woven fabric or single-layer gauze and applied to the affected area. The PC treatment was applied for 20 min, 2 or 3 times per day. All patients were followed up at 1 and 3 months. No visible warts remained after the cryotherapy and PC treatment. At the 1-month follow-up, only 1 case of recurrence was identified. At 3 months, 5 cases of recurrence were identified, and the recurrence rate was 10.9%. The satisfaction rate of the patients was 94% at 1 month and 87% at 3 months after treatment. All pregnancies resulted in healthy live births without delivery complications. Cryotherapy combined with PCs is indicated to be a safe and effective procedure and may serve as a treatment option for pregnant women with CA. PMID:27284325

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.

Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion

PubMed Central

Lee, Jae-Seon; Nam, Boas; Seong, Tae Wha; Son, Jaekyoung; Jang, Hyonchol; Hong, Kyeong Man; Lee, Cheolju; Kim, Soo-Youl

2016-01-01

Among ALDH isoforms, ALDH1L1 in the folate pathway showed highly increased expression in non-small-cell lung cancer cells (NSCLC). Based on the basic mechanism of ALDH converting aldehyde to carboxylic acid with by-product NADH, we suggested that ALDH1L1 may contribute to ATP production using NADH through oxidative phosphorylation. ALDH1L1 knockdown reduced ATP production by up to 60% concomitantly with decrease of NADH in NSCLC. ALDH inhibitor, gossypol, also reduced ATP production in a dose dependent manner together with decrease of NADH level in NSCLC. A combination treatment of gossypol with phenformin, mitochondrial complex I inhibitor, synergized ATP depletion, which efficiently induced cell death. Pre-clinical xenograft model using human NSCLC demonstrated a remarkable therapeutic response to the combined treatment of gossypol and phenformin. PMID:27384481

Comparison of glycemic control and β-cell function in new onset T2DM patients with PCOS of metformin and saxagliptin monotherapy or combination treatment.

PubMed

Tao, Tao; Wu, Peihong; Wang, Yuying; Liu, Wei

2018-02-27

Impaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China. A total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study. All patients received treatment for 24 weeks with metformin, saxagliptin, or their combination. Patients were allocated to one of three treatment groups by a computer-generated code that facilitated equal patient distribution of 25 patients per group. The primary outcome was a change in glycemic control and β-cell function. A total of 63 patients completed the study (n = 21, for each group). The reduction in hemoglobin A1c was significant in the combination group, compared to the monotherapy groups (saxagliptin vs. combination treatment vs. metformin: - 1.1 vs. -1.3 vs. -1.1%, P = 0.016), whereas it was comparable between the metformin and saxagliptin groups (P > 0.05). Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P < 0.01 for all). However, no significant change was observed in the homeostasis model assessment- β-cell function among the metformin and combination groups, and no significant changes were observed in the insulinogenic index among all three groups (P > 0.05 for all). In addition, saxagliptin and metformin treatments significantly reduced body mass index and high-sensitivity C-reactive protein levels (P < 0.01 for both). Saxagliptin and metformin were comparably effective in regulating weight loss, glycemic control, and β-cell function, improving lipid profiles, and

Comparison of risk assessment based on clinical judgement and Cariogram in addition to patient perceived treatment need.

PubMed

Hänsel Petersson, Gunnel; Åkerman, Sigvard; Isberg, Per-Erik; Ericson, Dan

2016-07-07

Predicting future risk for oral diseases, treatment need and prognosis are tasks performed daily in clinical practice. A large variety of methods have been reported, ranging from clinical judgement or "gut feeling" or even patient interviewing, to complex assessments of combinations of known risk factors. In clinical practice, there is an ongoing continuous search for less complicated and more valid tools for risk assessment. There is also a lack of knowledge how different common methods relates to one another. The aim of this study was to investigate if caries risk assessment (CRA) based on clinical judgement and the Cariogram model give similar results. In addition, to assess which factors from clinical status and history agree best with the CRA based on clinical judgement and how the patient's own perception of future oral treatment need correspond with the sum of examiners risk score. Clinical examinations were performed on randomly selected individuals 20-89 years old living in Skåne, Sweden. In total, 451 individuals were examined, 51 % women. The clinical examination included caries detection, saliva samples and radiographic examination together with history and a questionnaire. The examiners made a risk classification and the authors made a second risk calculation according to the Cariogram. For those assessed as low risk using the Cariogram 69 % also were assessed as low risk based on clinical judgement. For the other risk groups the agreement was lower. Clinical variables that significantly related to CRA based on clinical judgement were DS (decayed surfaces) and combining DS and incipient lesions, DMFT (decayed, missed, filled teeth), plaque amount, history and soft drink intake. Patients' perception of future oral treatment need correlated to some extent with the sum of examiners risk score. The main finding was that CRA based on clinical judgement and the Cariogram model gave similar results for the groups that were predicted at low level of future

Improving external beam radiotherapy by combination with internal irradiation.

PubMed

Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

2015-07-01

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

Is fixed combination therapy appropriate for initial hypertension treatment?

PubMed

Elliott, William J

2002-08-01

Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

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.

Combined Endovascular Treatment with Distal Radial Artery Coil Embolization and Angioplasty in Steal Syndrome Associated with Forearm Dialysis Fistula.

PubMed

Tercan, Fahri; Koçyiğit, Ali; Güney, Bünyamin

2016-09-01

The present study was performed to define the results of the endovascular treatment with angioplasty and distal radial artery embolization in ischemic steal syndrome associated with forearm arteriovenous accesses. The cases referred to our interventional radiology unit with symptoms and physical examination findings suggestive of ischemic steal syndrome were retrospectively evaluated first by Doppler ultrasonography, and then by angiography. Cases with proximal artery stenosis were applied angioplasty, and those with steal syndrome underwent coil embolization to distal radial artery. Of 589 patients who underwent endovascular intervention for dialysis arteriovenous fistulae (AVF)-associated problems, 6 (1.01 %) (5 female, 1 males; mean age 62 (range 41-78) with forearm fistula underwent combined endovascular treatment for steal syndrome. In addition to steal phenomenon, there were stenosis and/or occlusion in proximal radial and/or ulnar artery in 6 patients concurrently. Embolization of distal radial artery and angioplasty to proximal arterial stenoses were performed in all patients. Ischemic symptoms were eliminated in all patients and the AVF were in use at the time of study. In one patient, ischemic symptoms recurring 6 months later were alleviated by repeat angioplasty of ulnar artery. In palmar arch steal syndrome affecting forearm fistulae, combined distal radial embolization and angioplasty is also an effective treatment method in the presence of proximal radial and ulnar arterial stenoses and occlusions.

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.

Combination of Anti-angiogenesis with Chemotherapy for More Effective Cancer Treatment*

PubMed Central

Ma, Jie; Waxman, David J.

2008-01-01

Angiogenesis is a hallmark of tumor development and metastasis and is now a validated target for cancer treatment. Overall, however, the survival benefits of anti-angiogenic drugs have, thus far, been rather modest, stimulating interest in developing more effective ways to combine anti-angiogenic drugs with established chemotherapies. This review discusses recent progress and emerging challenges in this field; interactions between anti-angiogenic drugs and conventional chemotherapeutic agents are examined, and strategies for the optimization of combination therapies are discussed. Anti-angiogenic drugs such as the anti-VEGF antibody bevacizumab can induce a functional normalization of the tumor vasculature that is transient and can potentiate the activity of co-administered chemoradiotherapies. However, chronic angiogenesis inhibition typically reduces tumor uptake of co-administered chemotherapeutics, indicating a need to explore new approaches, including intermittent treatment schedules and provascular strategies to increase chemotherapeutic drug exposure. In cases where anti-angiogenesis-induced tumor cell starvation augments the intrinsic cytotoxic effects of a conventional chemotherapeutic drug, combination therapy may increase anti-tumor activity despite a decrease in cytotoxic drug exposure. As new angiogenesis inhibitors enter the clinic, reliable surrogate markers are needed to monitor the progress of anti-angiogenic therapies and to identify responsive patients. New targets for anti-angiogenesis continue to be discovered, increasing the opportunities to interdict tumor angiogenesis and circumvent resistance mechanisms that may emerge with chronic use of these drugs. PMID:19074844

Obstructive sleep apnea combined dyslipidemia render additive effect on increasing atherosclerotic cardiovascular diseases prevalence.

PubMed

Cao, Zhiyong; Zhang, Ping; He, Zhiqing; Yang, Jing; Liang, Chun; Ren, Yusheng; Wu, Zonggui

2016-05-26

Current study was designed to investigate the effects of obstructive sleep apnea (OSA) combined dyslipidemia on the prevalence of atherosclerotic cardiovascular diseases (ASCVD). This was a cross-sectional study and subjects with documented dyslipidemia and without previous diagnosis of OSA were enrolled. Polysomnography was applied to evaluate apnea-hypopnea index (AHI). Based on AHI value, subjects were classified into four groups: without OSA, mild, moderate and severe OSA groups. Clinical characteristics and laboratory examination data were recorded. Relationship between AHI event and lipid profiles was analyzed, and logistic regression analysis was used to evaluate the effects of OSA combined dyslipidemia on ASCVD prevalence. Totally 248 subjects with dyslipidemia were enrolled. Compared to the other 3 groups, subjects with severe OSA were older, male predominant and had higher smoking rate. In addition, subjects with severe OSA had higher body mass index, waist-hip ratio, blood pressure, and higher rates of overweight and obesity. Serum levels of fasting plasma glucose, glycated hemoglobin, LDL-C and CRP were all significantly higher. ASCVD prevalence was considerably higher in subjects with severe OSA. AHI event in the severe OSA group was up to 35.4 ± 5.1 events per hour which was significantly higher than the other groups (P < 0.05 for trend). Pearson correlation analysis showed that only LDL-C was positively correlated with AHI events (r = 0.685, P < 0.05). Logistic regression analysis revealed that in unadjusted model, compared to dyslipidemia plus no-OSA group (reference group), OSA enhanced ASCVD risk in subjects with dyslipidemia, regardless of OSA severity. After extensively adjusted for confounding variables, the odds of dyslipidemia plus mild-OSA was reduced to insignificance. While the effects of moderate- and severe-OSA on promoting ASCVD risk in subjects with dyslipidemia remained significant, with severe-OSA most prominent (odds ratio: 1

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

Additive effects of plant sterols supplementation in addition to different lipid-lowering regimens.

PubMed

Malina, Daniela M T; Fonseca, Francisco A; Barbosa, Sílvio A; Kasmas, Soraia H; Machado, Valéria A; França, Carolina N; Borges, Ney C; Moreno, Ronilson A; Izar, Maria C

2015-01-01

Plant sterol (PS) supplementation has been widely used alone or combined with lipid-lowering therapies (LLTs) to reduce low-density lipoprotein (LDL) cholesterol. The effects of PS added to high-intensity LLT are less reported, especially regarding the effects on cholesterol synthesis and absorption. A prospective, randomized, open-label study, with parallel arms and blinded end points was designed to evaluate the effects of addition of PS to LLT on LDL cholesterol, markers of cholesterol synthesis, and absorption. Eighty-six patients of both genders were submitted to a 4-wk run-in period with atorvastatin 10 mg (baseline). Following, subjects received atorvastatin 40 mg, ezetimibe 10 mg, or combination of both drugs for another 4-wk period (phase I). In phase II, capsules containing 2.0 g of PSs were added to previous assigned treatments for 4 wk. Lipids, apolipoproteins, plasma campesterol, β-sitosterol, and desmosterol levels were assayed at all time points. Within and between-group analyses were performed. Compared with baseline, atorvastatin 40 mg reduced total and LDL cholesterol (3% and 22%, respectively, P < .05), increased β-sitosterol, campesterol/cholesterol, and β-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, P < .05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, P < .05), and the combined therapy decreased total and LDL cholesterol (22% and 38%, respectively, P < .05), campesterol, β-sitosterol, and campesterol/cholesterol ratio (54%, 40%, and 27%, P < .05). Addition of PS further reduced total and LDL cholesterol by ∼ 7.7 and 6.5%, respectively, in the atorvastatin therapy group and 5.0 and 4.0% in the combined therapy group (P < .05, for all), with no further effects in absorption or synthesis markers. PS added to LLT can further improve lipid profile, without additional effects on intestinal sterol absorption or synthesis. Copyright © 2015 National Lipid Association

Combination therapy in combating cancer

PubMed Central

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

2017-01-01

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

Experimental additions of aluminum sulfateand ammonium nitrate to in situ mesocosms toreduce cyanobacterial biovolume and microcystinconcentration

USGS Publications Warehouse

Harris, Theodore D.; Wilhelm, Frank M.; Graham, Jennifer L.; Loftin, Keith A.

2014-01-01

Recent studies suggest that nitrogen additions to increase the total nitrogen:total phosphorus (TN:TP) ratio may reduce cyanobacterial biovolume and microcystin concentration in reservoirs. In systems where TP is >100 μg/L, however, nitrogen additions to increase the TN:TP ratio could cause ammonia, nitrate, or nitrite toxicity to terrestrial and aquatic organisms. Reducing phosphorus via aluminum sulfate (alum) may be needed prior to nitrogen additions aimed at increasing the TN:TP ratio.We experimentally tested this sequential management approach in large in situ mesocosms (70.7 m3) to examine effects on cyanobacteria and microcystin concentration. Because alum removes nutrients and most seston from the water column, alum treatment reduced both TN and TP, leaving post-treatment TN:TP ratios similar to pre-treatment ratios. Cyanobacterial biovolume was reduced after alum addition, but the percent composition (i.e., relative) cyanobacterial abundance remained unchanged. A single ammonium nitrate (nitrogen) addition increased the TN:TP ratio 7-fold. After the TN:TP ratio was >50 (by weight), cyanobacterial biovolume and abundance were reduced, and chrysophyte and cryptophyte biovolume and abundance increased compared to the alum treatment. Microcystin was not detectable until the TN:TP ratio was <50. Although both treatments reduced cyanobacteria, only the nitrogen treatment seemed to stimulate energy flow from primary producers to zooplankton, which suggests that combining alum and nitrogen treatments may be a viable in-lake management strategy to reduce cyanobacteria and possibly microcystin concentrations in high-phosphorus systems. Additional studies are needed to define best management practices before combined alum and nitrogen additions are implemented as a reservoir management strategy.

Effect of tamoxifen, methoxyprogesterone acetate and combined treatment on cellular proliferation and apoptosis in SKOV3/DDP cells via the regulation of vascular endothelial growth factor.

PubMed

Wen, Lv; Hong, Ding; Yanyin, Wu; Mingyue, Zhang; Baohua, Li

2013-05-01

The aim of this study was to investigate the effect of tamoxifen (TAM), methoxyprogesterone acetate (MPA) and their combined treatment on cisplatin-resistant ovarian cancer SKOV3/DDP cells, as well as the potential mechanisms. MTT assay was used to investigate the effect of different concentrations (0.01, 0.1, 1, 10 and 100 μM) of TAM, MPA and their combined treatment on the proliferation of cisplatin-resistant ovarian cancer SKOV3/DDP cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of SKOV3/DDP cells treated with medium concentration (10 μM) of TAM, MPA and their combined treatment. Change in the protein level of vascular endothelial growth factor (VEGF) in response to drug treatments was measured using Western-blot. The proliferation of SKOV3/DDP cells was inhibited by 1, 10 and 100 μM of TAM or MPA in a dose-dependent manner. Compared to the control group, 10 μM TAM could significantly arrest SKOV3/DDP cells in the G0/G1 stage and induce apoptosis (p < 0.01). However, 10 μM MPA only promoted cell apoptosis, while exhibited little effect on the cell cycle. We further found that 10 μM TAM could remarkably reduce the protein expression of VEGF, while 10 μM MPA only induce a slight reduction. Strikingly, the combined treatment of TAM and MPA exhibited additive effect on the proliferation, cell cycle, apoptosis rate and VEGF expression of SKOV3/DDP cells. We found that TAM, MPA and their combined treatment exhibited significant inhibitory effect on the cisplatin-resistant ovarian cancer SKOV3/DDP cells. Hence, TAM and MPA could be potential cytotoxic drugs to treat cisplatin-resistant patients with advanced ovarian cancer.

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

2018-01-01

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

Combined effects of high pressure homogenization treatment and citral on microbiological quality of apricot juice.

PubMed

Patrignani, Francesca; Tabanelli, Giulia; Siroli, Lorenzo; Gardini, Fausto; Lanciotti, Rosalba

2013-01-01

High pressure homogenization (HPH) technique is able to significantly reduce spoilage microbiota in fruit juice. On the other hand, aroma compounds and essential oils can have a key role in the microbial stability of these products. For this reason, the aim of this work was to evaluate the combined effects of an aroma compound (citral, used at a concentration of 50 mg/l) and HPH treatments (performed at 100 MPa for 1-8 successive passes) on the inactivation dynamics of Saccharomyces cerevisiae SPA strain inoculated in apricot juices at level of about 4.5 log CFU/ml. Moreover, growth of surviving yeast cells was measured during the storage of the treated juice at 10°C and pH, water activity, viscosity and volatile molecule profile of apricot juice were studied. Since citral had been diluted in ethanol before the addition to juice, also samples with only ethanol added at the same volume used to dissolve citral were considered. The results showed that yeast cell viability decreased with the increases of passes at 100 MPa and the relationship between yeast cell loads and number of passes at 100 MPa followed a linear trend. In addition, the effect of HPH treatment can be notably potentiated throughout the presence of citral and ethanol, increasing the time necessary to reach a spoilage threshold during storage. The volatile profiles of the juices added with citral showed a substitution by yeast metabolism of this aldehyde with molecule characterized by a lower antimicrobial activity such as alcohols. The HPH treatments had also a significant effect on pH and viscosity of apricot juices while did not affect a(w). Copyright © 2012 Elsevier B.V. All rights reserved.

Combined treatment: impact of optimal psychotherapy and medication in bipolar disorder.

PubMed

Parikh, Sagar V; Hawke, Lisa D; Velyvis, Vytas; Zaretsky, Ari; Beaulieu, Serge; Patelis-Siotis, Irene; MacQueen, Glenda; Young, L Trevor; Yatham, Lakshmi N; Cervantes, Pablo

2015-02-01

The current study investigated the longitudinal course of symptoms in bipolar disorder among individuals receiving optimal treatment combining pharmacotherapy and psychotherapy, as well as predictors of the course of illness. A total of 160 participants with bipolar disorder (bipolar I disorder: n = 115; bipolar II disorder: n = 45) received regular pharmacological treatment, complemented by a manualized, evidence-based psychosocial treatment - that is, cognitive behavioral therapy or psychoeducation. Participants were assessed at baseline and prospectively for 72 weeks using the Longitudinal Interval Follow-up Evaluation (LIFE) scale scores for mania/hypomania and depression, as well as comparison measures (clinicaltrials.gov identifier: NCT00188838). Over a 72-week period, patients spent a clear majority (about 65%) of time euthymic. Symptoms were experienced more than 50% of the time by only a quarter of the sample. Depressive symptoms strongly dominated over (hypo)manic symptoms, while subsyndromal symptoms were more common than full diagnosable episodes for both polarities. Mixed symptoms were rare, but present for a minority of participants. Individuals experienced approximately six significant mood changes per year, with a full relapse on average every 7.5 months. Participants who had fewer depressive symptoms at intake, a later age at onset, and no history of psychotic symptoms spent more weeks well over the course of the study. Combined pharmacological and adjunctive psychosocial treatments appeared to provide an improved course of illness compared to the results of previous studies. Efforts to further improve the course of illness beyond that provided by current optimal treatment regimens will require a substantial focus on both subsyndromal and syndromal depressive symptoms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: systematic review and meta-analysis.

PubMed

Martínez-Vázquez, M A; Vázquez-Elizondo, G; González-González, J A; Gutiérrez-Udave, R; Maldonado-Garza, H J; Bosques-Padilla, F J

2012-01-01

Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS. We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI. Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations. Copyright © 2011 Asociación Mexicana de Gastroenterología. Published by Elsevier España. All rights reserved.

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

PubMed

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

2017-05-19

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

Two-year evaluation of Intermittent Preventive Treatment for Children (IPTc) combined with timely home treatment for malaria control in Ghana.

PubMed

Ahorlu, Collins K; Koram, Kwadwo A; Seake-Kwawu, Atsu; Weiss, Mitchell G

2011-05-15

Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. Intermittent preventive treatment for children (IPTc) combined with timely treatment of malaria related febrile illness at home to reduce parasite prevalence and malaria morbidity in children aged between six and 60 months in a coastal community in Ghana. This paper reports persistence of reduced parasitaemia two years into the intervention. The baseline and year-one-evaluation findings were published earlier. The main objective in the second year was to demonstrate whether the two interventions would further reduce parasite prevalence and malaria-related febrile illness in the study population. This was an intervention study designed to compare baseline and evaluation findings without a control group. The study combined home-based delivery of intermittent preventive treatment for children (IPTc) aged 6 - 60 months and home treatment of suspected febrile malaria-related illness within 24 hours. All children aged 6-60 months received home-based delivery of intermittent preventive treatment using amodiaquine + artesunate, delivered at home by community assistants every four months (6 times in 24 months). Malaria parasite prevalence surveys were conducted before the first and after the third and sixth IPTc to the children. The evaluation surveys were done four months after the third and sixth IPTc was given. Parasite prevalence which reduced from 25% to 3.0% at year-one evaluation had reduced further from 3% to 1% at year-two-evaluation. At baseline, 13.8% of the children were febrile (axilary temperature of ≥ 37.5 °C) compared to 2.2% at year-one-evaluation while 2.1% were febrile at year-two-evaluation. The year-two-evaluation result indicates that IPTc given three times in a year (every four months) combined with timely treatment of febrile malaria illness, is effective to reduce malaria parasite prevalence in children aged 6 to 60 months

Comparison of water wash, trimming, and combined hot water and lactic acid treatments for reducing bacteria of fecal origin on beef carcasses.

PubMed

Castillo, A; Lucia, L M; Goodson, K J; Savell, J W; Acuff, G R

1998-07-01

Cleaning treatments, such as high-pressure water wash at 35 degrees C or trim, alone and combined with sanitizing treatments, such as hot water (95 degrees C at the source), warm (55 degrees C) 2% lactic acid spray, and combinations of these two sanitizing methods, were compared for their effectiveness in reducing inoculated numbers (5.0 to 6.0 log CFU/cm2) of Salmonella typhimurium, Escherichia coli O157:H7, aerobic plate counts, Enterobacteriaceae, total coliforms, thermotolerant coliforms, and generic E. coli on hot beef carcass surface areas in a model carcass spray cabinet. Log reductions in numbers of all tested organisms by water wash or trim alone were significantly smaller than the log reductions obtained by the different combined treatments. Regardless of the cleaning treatment (water wash or trim) or surface area, the range for mean log reductions by hot water was from 4.0 to > 4.8 log CFU/cm2, by lactic acid spray was from 4.6 to > 4.9 log CFU/cm2, by hot water followed by lactic acid spray was from 4.5 to > 4.9 log CFU/cm2, and by lactic acid spray followed by hot water was from 4.4 to > 4.6 log CFU/cm2, for S. typhimurium and E. coli O157:H7. Identical reductions were obtained for thermotolerant coliforms and generic E. coli. No differences in bacterial reductions were observed for different carcass surface regions. Water wash and trim treatments caused spreading of the contamination to other areas of the carcass surface while providing an overall reduction in fecal or pathogenic contamination on carcass surface areas. This relocated contamination after either water wash or trim was most effectively reduced by following with hot water and then lactic acid spray. This combined treatment yielded 0% positive samples for S. typhimurium, E. coli O157:H7, thermotolerant coliforms, and generic E. coli on areas outside the inoculated areas, whereas percent positive samples after applying other combined treatments ranged from 22 to 44% for S. typhimurium, 0 to

Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer

PubMed Central

Lucena, Silvia Rocío; Salazar, Nerea; Gracia-Cazaña, Tamara; Zamarrón, Alicia; González, Salvador; Juarranz, Ángeles; Gilaberte, Yolanda

2015-01-01

Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer. PMID:26516853

Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer.

PubMed

Lucena, Silvia Rocío; Salazar, Nerea; Gracia-Cazaña, Tamara; Zamarrón, Alicia; González, Salvador; Juarranz, Ángeles; Gilaberte, Yolanda

2015-10-28

Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer.

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.

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.

Landfill Leachate Toxicity Removal in Combined Treatment with Municipal Wastewater

PubMed Central

Kalka, J.

2012-01-01

Combined treatment of landfill leachate and municipal wastewater was performed in order to investigate the changes of leachate toxicity during biological treatment. Three laboratory A2O lab-scale reactors were operating under the same parameters (Q-8.5–10 L/d; HRT-1.4–1.6 d; MLSS 1.6–2.5 g/L) except for the influent characteristic and load. The influent of reactor I consisted of municipal wastewater amended with leachate from postclosure landfill; influent of reactor II consisted of leachate collected from transient landfill and municipal wastewater; reactor III served as a control and its influent consisted of municipal wastewater only. Toxicity of raw and treated wastewater was determinted by four acute toxicity tests with Daphnia magna, Thamnocephalus platyurus, Vibrio fischeri, and Raphidocelis subcapitata. Landfill leachate increased initial toxicity of wastewater. During biological treatment, significant decline of acute toxicity was observed, but still mixture of leachate and wastewater was harmful to all tested organisms. PMID:22623882

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

PubMed

Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

2017-08-01

In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

A fixed-dose combination of memantine extended-release and donepezil in the treatment of moderate-to-severe Alzheimer's disease.

PubMed