Efficacy Of Various Combinations Research Articles

Evaluation of novel cosmetic shampoo formulations against Malassezia species: Preliminary results of anti-dandruff shampoo formulations.

Malassezia species are common, clinically relevant, and lipid-dependent yeasts of humans. They are also the leading causes of the dandruff problem of humans, and the azoles are used primarily in their topical and systemic treatment. Resistance to azoles is an emerging problem among Malassezia sp., which indicates the need of new drug assessments that will be effective against dandruff and limit the use of azoles and other agents in treatment. Among them, the efficacy of various combinations of piroctone olamine and climbazole against Malassezia sp. ishighly important. Here, we assessed the efficacies of various piroctone olamine and climbazole formulations against Malassezia sp. in comparison with ketoconazole. A total of nine formulations were included in the study, where each formulation was prepared from different concentrations of piroctone olamine and climbazole and both. All formulations contained the same ingredients as water, surfactants, hair conditioning agents, and preservatives. Malassezia furfur CBS1878, Malassezia globosa CBS7874, and Malassezia sympodialis CBS9570 were tested for antifungal susceptibility of each formulation by agar diffusion method. Sizes of the inhibition zones were compared with standard medical shampoo containing 2% ketoconazole, and the data were analyzed by Dunnett's multiple-comparison test. For all Malassezia sp. strains, climbazole 0.5% and piroctone olamine/climbazole (0.1%/0.1% and 0.1%/0.5%) combinations were found to have the same effect as the medical shampoo containing 2% ketoconazole. Piroctone olamine/climbazole 1.0%/0.1% formulation showed the same efficacy as 2% ketoconazole on M. furfur and M. sympodialis, while 0.1%/0.5% formulation to only M. furfur. For M. globosa, none of the formulations tested were as effective as ketoconazole. The species distribution of Malassezia sp. varies depending on the anatomical location on the host. According to the results of this study, climbazole and piroctone olamine combinations seem to be promising options against the dandruff problem with their high antifungal/anti dandruff efficacy.

Taoist way of a balanced exercise training cocktail for the management of primary hypertension in older persons.

High blood pressure is the world's leading risk factor for mortality, affecting nearly half of the global population aged 50-79 years. Physical inactivity is one factor contributing to the prevalence of hypertension. This paper discusses a new concept for the management of hypertension in older persons. We are inclined to fade the current guidelines used in China, the United States, and Europe. Although demonstrating irrefutable benefits for blood pressure regulation, the guidelines fail to address the need to incorporate balance exercises, which are crucial for mitigating the risk of falling. We address three pressing questions regarding the efficacy of various combinations of exercise modes for blood pressure regulation, alongside providing an overview of balance exercises. At the core of our concept, we explicate the challenges inherent in addressing the global pandemic of physical inactivity and hypertension in regular socioeconomic people. No guidelines could change the state of inactivity by jumping between zero and all things, where "zero" symbolizes conditions such as physical inactivity and hypertension, and the concept of "all things" encompasses the ideals of an active lifestyle and healthy aging. We advocate a Taoist way, "zero-one-all things," where "one" in this context refers to an inclusive and culturally diverse exercise training cocktail. The Tao guides us to illuminate an ancient way of overcoming physical inactivity-associated diseases in the present day.

Possibilities of combination treatment of urinary incontinence in women of different age groups

The effectiveness of conservative therapy in patients with urinary incontinence depends on a variety of factors. There are no clinical guidelines for the use of pharmacological and non-pharmacological treatment concepts for women of reproductive and menopausal age. The aim of the study was evaluating the efficacy of various combinations of treatment for patients with urinary incontinence, based on electrical stimulation of the pelvic floor muscles with biofeedback, fractional photothermolysis with a CO2‑laser, and medications (antimuscarinics, selective β3‑agonist). The prospective randomized study included 105 patients, of whom 20 were of reproductive age and 85 were of menopausal age. The patients were divided into three groups: group 1 included the patients who underwent a course of electrical stimulation of the pelvic floor muscles and photothermolysis (with fractional CO2‑laser); in group 2, the patients received a combination of non-drug treatment and medications; in group 3, the patients receivedonly pharmacological treatment. In group 1, there were 7 patients of reproductive age and 28 menopausal patients, in group 2–5 and 30, and in group 3–8 and 27 patients, respectively. Results. The bladder diary scores improved significantly. Increasing the urinary flow rate was more effective with non-pharmacological treatment in young patients, and reducing the frequency of urination was more efficient with drug therapy in menopausal patients. The probability of achieving a urinary frequency of less than 8 times per day in the combination treatment group was 80 % higher than that in the non-drug treatment group and 62 % higher than that in the drug treatment group. The effectiveness of non-pharmacological therapy in increasing urinary flow rate is higher in patients of reproductive age. Pharmacological treatment is more effective for three months in menopausal women. The combination treatment is equally effective in patients aged 35 to 65 years and is superior in total effect to drug and non-drug treatment, with the effect maintaining for up to 6 months in menopausal patients.

EDGE-Gastric Arm A1: Phase 2 study of domvanalimab, zimberelimab, and FOLFOX in first-line (1L) advanced gastroesophageal cancer.

433248 Background: The addition of programmed cell death protein 1 (PD-1) inhibitors to chemotherapy (chemo) confers a survival advantage in 1L gastroesophageal cancers. However, long term outcomes remain poor. Dual PD-1 and anti-T-cell immunoglobulin and ITM domain (TIGIT) blockade increases tumor antigen-specific CD8+ T cell expansion, resulting in potent antitumor activity. The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the anti-TIGIT Fc-silent monoclonal antibody (mAb) domvanalimab (D) and the anti-PD-1 mAb zimberelimab (Z) in patients (pts) with locally advanced unresectable or metastatic gastric (G)/gastroesophageal junction (GEJ)/esophageal (E) adenocarcinoma. Arm A1 is fully enrolled and results from this 1L arm are presented here. Methods: Patients with previously untreated G/GEJ/E adenocarcinoma received D 1600 mg intravenously (IV) every 4 weeks (Q4W) + Z 480 mg IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) Q2W. Primary endpoints are safety and objective response rate (ORR) per RECIST 1.1. Secondary endpoints include ORR by PD-L1 expression and PFS. Results: As of the data cutoff (5 June 2023), 41 pts were enrolled and had the opportunity to have ≥2 imaging assessments. There was an even distribution of pts accrued in Asia vs. rest of world and 63% of pts had gastric cancer. Median time on treatment was 23 weeks (1 to 40), 31 pts (76%) continue on protocol therapy, and there were no deaths on study. Intent-to-treat ORR was 59% (95% CI 42 to 74). Clinical outcomes by PD-L1 status are in the Table. The most common treatment-emergent adverse events (TEAE) were neutropenia (56% of pts), nausea (54%), and anemia (27%). Infusion related reactions were observed in 10% and none were deemed related to D/Z. Grade ≥3 TEAEs occurred in 66% pts, with 54% and 12% having grade ≥3 TEAEs related to FOLFOX and D/Z, respectively. Serious TEAEs occurred in 24% pts: 7% had serious TEAEs related to FOLFOX and no pts had serious TEAEs related to D/Z. TEAE related FOLFOX discontinuation occurred in 13 pts (32%), and in 1 pt due to D/Z. Conclusions: Addition of DZ to FOLFOX showed encouraging ORR and early PFS, particularly in pts with PD-L1-high tumors. The regimen is well tolerated, with a similar AE profile to anti-PD-1+FOLFOX. Updated safety and efficacy will be presented. The randomized phase 3 1L STAR-221 trial of DZ+chemo vs. SOC is underway. Clinical trial information: NCT05329766 . [Table: see text]

Conceptual cost estimation of highway bid unit prices using ordinary kriging

State-of-the-art encompasses the application of deterministic and geostatistical algorithms to quantify the effect of spatial variation of unit prices across different locations. No studies have evaluated the efficacy of the different combinations of variogram and kriging models when used to characterize the spatial variability of major highway bid unit prices, as well as how well they predict future unit prices at unsampled locations. In this paper, ordinary kriging was combined with three commonly used semivariograms (spherical, exponential, Gaussian) models one at a time to predict six years of the top five common highway bid items obtained from the Wisconsin Department of Transportation (WisDOT) and evaluated the prediction uncertainty for each bid item. The results show that the best-performing combination of ordinary kriging and semivariogram varied depending on the type of bid unit-price data. This study advances the state of practice by comparing the efficacy of various combinations of the variogram and ordinary kriging models in predicting highway bid unit prices and provides insight into the models’ behavior in describing bid unit price spatial heterogeneity. Transportation agencies can employ this methodology to model other highway bid items and project types that have not been experimented in this study.

Effect of Modified Atmospheric Packaging on Physico-chemical Properties and Puncture Strength of Banarasi Langra Mango (Mangifera indica)

Background: Mango (Mangifera indica L.), a perishable tropical climatic fruit, has a short post-harvest life. Modified atmospheric packaging is an efficient way to keep their quality safe during extended storage. This study aims to assess the efficacy of various combinations of gas concentrations under MAP. Methods: Mature green mangoes were subjected to a hot water dip (40°C) for 30 min which was followed by packaging in polyethylene pouches under two different MAP gas concentrations and stored for 25 days at 10 and 15°C for physico-chemical analysis and texture profile analysis. Result: Warm water dip (40°C) for 30 min was the most effective post-harvest storage condition, followed by packaging in poly bags under MAP gas combination, i.e., O2- 7%: CO2- 50%. The keeping quality of 25 days was achieved significantly better than the control samples, which showed deterioration after 12 days of storage.

A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.

Although treatment options for melanoma patients have expanded in recent years with the approval of immunotherapy and targeted therapy, there is still an unmet need for new treatment options for patients that are ineligible for, or resistant to these therapies. BH3 mimetics, drugs that mimic the activity of pro-apoptotic BCL2 family proteins, have recently achieved remarkable success in the clinical setting. The combination of BH3 mimetic ABT-199 (venetoclax) plus azacitidine has shown substantial benefit in treating acute myelogenous leukemia. We evaluated the efficacy of various combinations of BH3 mimetic + azacitidine in fourteen human melanoma cell lines from cutaneous, mucosal, acral and uveal subtypes. Using a combination of cell viability assay, BCL2 family knockdown cell lines, live cell imaging, and sphere formation assay, we found that combining inhibition of MCL1, an anti-apoptotic BCL2 protein, with azacitidine had substantial pro-apoptotic effects in multiple melanoma cell lines. Specifically, this combination reduced cell viability, proliferation, sphere formation, and induced apoptosis. In addition, this combination is highly effective at reducing cell viability in rare mucosal and uveal subtypes. Overall, our data suggest this combination as a promising therapeutic option for some patients with melanoma and should be further explored in clinical trials.

Curative Evaluation of Biological Control Agents and Synthetic Fungicides for Clarireedia jacksonii

Clarireedia jacksonii sp. nov. formerly Sclerotinia homoeocarpa F.T. Bennett, one of the causal agents of dollar spot, is the most widespread pathogen in turfgrass systems. Dollar spot (DS) affects both cool- and warm-season grasses, during a wide range of environmental conditions. Field studies were conducted at Clemson University, Clemson, SC, on a creeping bentgrass [Agrostis stolonifera L. var. palustris (Huds) cv. Crenshaw] putting green for 2 consecutive years from August to October in year 1 and July to September in year 2. The objective of the studies was to evaluate biological control agents (BCAs) and synthetic fungicides at reduced rates for their efficacy controlling dollar spot. Four replications of 1.5 × 1.5-m plots were used in the experimental design. Treatments included the following: Bacillus subtilis (BS); plant extract oils (EO) including clove oil + wintergreen oil + thyme oil; extract of Reynoutria sachalinensis (RS); Bacillus licheniformis (BL); chlorothalonil (CL); and azoxystrobin + propiconazole (AzP). Synthetic fungicides were used at reduced rates in combination with biological control agents, to evaluate curative control efficacy of various combinations. All reduced synthetic programs, except CL + EO, provided acceptable disease severity (≤15%) at the end of year 1 and acceptable (≥7) turfgrass visual quality. Azoxystrobin + propiconazole, CL, AzP + BL, AzP + EO, AzP + BS all provided ≤15% disease severity and ≥7 visual turfgrass quality 14 days after the last application in year 2.

A Comparative Performance Evaluation of 2D Nanomaterials for Applications in Plasmonic Biosensing

Plasmonic sensing relies on the interaction between the electromagnetic light wave and free electrons that reside at the interface of two materials, one of them being a metal. Surface plasmon resonance (SPR)‐based biosensing has distinct advantages of providing real‐time and label‐free detection technique that is capable of giving accurate and repeatable results. 2D nanomaterials (graphene and transition metal dichalcogenides [TMDCs] such as MoS2 and WS2) have recently gained high popularity in the field of biomedical sciences. Using Biacore commercial SPR machine manufactured by GE Healthcare, the efficacy of various combinations of these materials coated on the plasmonic metal gold (Au) (Au + MoS2, Au + WS2, Au + graphene, Au + graphene + MoS2, and Au + graphene + WS2) is evaluated, in enhancing the sensitivity of the biosensor as compared with the standard Kretschmann configuration (only Au). Some simulation results are also presented at incident light wavelengths of 633 and 785 nm that are based on the angular interrogation method. To conclude, it is found that the sensitivity in the increasing order is: only Au < Au + MoS2 < Au + WS2 ≈ Au + graphene < Au + graphene + MoS2 < Au + graphene + WS2.

N-acetylglucosamine increases the efficacy of quercetin in the treatment of experimental acute kidney injury

Context: Acute kidney injury (AKI) is a common complication of renal pathology and an adverse drug effect. Mortality caused by AKI reaches 80% in some groups of patients. Therefore, the search of the effective agents for AKI treatment is an important task of the pharmaceutical science. Aims: To evaluate the efficacy of various combinations of N-acetylglucosamine (NAG) and quercetin in rats with AKI. Methods: The study was conducted on the model of acute glycerol nephrosis in rats. Combinations of NAG and quercetin in ratios of 1:2, 1:1, 2:1 and 3:1 were studied at a dose of 50 mg/kg with daily intramuscular injection for a week. The efficacy of the combinations was assessed by the indicators of animal survival, excretory renal function, nitrogen metabolism and nephroprotective activity (NA). Results: The combination of NAG and quercetin in the 1:1 ratio was the most effective. There was a significant increase of excretory renal function and normalization of nitrogen metabolism under the influence of this combination. This determined the NA level up to 69.7%, which was the highest value in the presented study. This combination was statistically superior to all others, as well as to quercetin, by the efficacy level. In addition, the combination exceeded the quercetin in NA index by 2.7 times. Conclusions: Thus, the NAG/quercetin combination in 1:1 ratio in injectable dosage form is the most promising for kidney diseases treatment.

Multi and extensively drug-resistant pulmonary tuberculosis: advances in diagnosis and management.

Multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB epidemics are key obstacles towards TB control and elimination. Diagnosis of MDR/XDR-TB is difficult and requires several weeks. New diagnostic tools are being tested and proposed allowing for shorter time to diagnosis and reduced delays in starting an adequate treatment regimen. MDR/XDR-TB treatment strategies are currently on an evolving stage. New shortened treatments based on the recommended 'Bangladesh regimen' or on the newer anti-TB drugs, delamanid and bedaquiline may represent part of the future scenario. In addition, more information on safety and efficacy of delamanid and bedaquiline has been published, allowing to better position these drugs. Recent information on treatment regimens for the paediatric age, with or without delamanid or bedaquiline, has become available. This is of great help in designing safer and more efficacious regimens for the treatment of MDR/XDR-TB in children and adolescents. The accessibility, sustainability and scale-up of new diagnostic technologies are lagging behind and more efforts are needed. In addition, we need high-quality information on safety and efficacy of various combinations of drugs to obtain the best possible regimens to treat the largest possible proportion of patients.

Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats

Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.

Abstract OT2-01-02: COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC)

Abstract Preclinical data suggest that upregulation of the MAPK pathway confers resistance to taxane chemotherapy. Mutations and gene amplifications in the MAPK pathway are present in many TNBC tumors and may contribute to taxane resistance. Preliminary data from an initial safety run-in stage of the COLET study (ClinicalTrials.gov ID, NCT02322814; EudraCT number, 2014-002230-32) suggest improvement of clinical outcomes when MEK inhibition is combined with taxane chemotherapy. Additionally, in preclinical models, MEK inhibition was shown to enhance anti–PD-L1 activity. The monoclonal antibody PD-L1 inhibitor atezo has shown promising activity in combination with nab-P in metastatic TNBC. Accordingly, the COLET protocol was amended to include the evaluation of triplet regimens combining atezo with MEK inhibition and taxane chemotherapy[SL1] . COLET is evaluating the safety and efficacy of various combinations of C as first-line treatment for metastatic or locally advanced TNBC. Key eligibility criteria include measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) and left ventricular ejection fraction > institutional lower limit of normal or >50%. Neoadjuvant or adjuvant therapy is allowed if completed >6 months prior to study entry. COLET has 3 cohorts: I, II, and III. Cohort I has 2 stages: an initial safety run-in stage (n∼12) followed by an expansion stage (n∼90) of 1:1 randomization to C + P or placebo (PBO) + P. Patients received P 80 mg/m2 on days 1, 8, and 15 and C/PBO 60 mg/day on days 3-23 of each 28-day cycle. In the expansion stage of Cohort I, randomization is stratified by prior neoadjuvant/adjuvant taxane therapy and disease-free interval from last chemotherapy dose. Cohorts II and III will evaluate the safety and efficacy of adding atezo to C + P or nab-P, respectively. Each cohort has a safety run-in stage (n∼15) and an expansion stage (additional n∼15); each will receive atezo 840 mg on days 1 and 15 and C 60 mg/day on days 3-23 of every 28-day cycle. Cohort II will receive P 80 mg/m2 and Cohort III will receive intravenous nab-P 100 mg/m2 on days 1, 8, and 15. Patients will receive treatment until disease progression or toxicity. The primary efficacy end point is investigator-assessed progression-free survival (PFS) for the expansion stage (Cohort I), and the primary PFS analysis will be performed when 60 PFS events occur across the 2 arms. This provides 77% power to detect a hazard ratio of 0.5 at a two-sided significance level of 0.05. For Cohorts II and III, the primary efficacy end point is overall response rate per RECIST v1.1; secondary end points include duration of response, PFS, and overall survival. Recruitment into the safety run-in stage of Cohort I is complete. Accrual into the randomization stage of Cohort I and the initial safety run-in stage of Cohorts II and III are ongoing. Patients from sites across North America, Europe, and the Asia-Pacific region will be enrolled. Citation Format: Miles D, Kim S-B, McNally V, Simmons B, Wongchenko M, Xu N, Brufsky A. COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-02.

COMPUTATIONAL STUDIES OF DUSPARSAKADI KWATHA AN AYURVEDIC CLASSICAL MEDICINE FOR HEMORRHOIDS

There are many methods to theoretically compute the efficacies of modern medicaments. These methodologies are not suitable for computing the efficacies of formulations used in Alternative Systems of Medicines especially to Ayurvedic formulations. In this paper a computational method developed earlier for computing the Drug Efficacy Indices of Ayurvedic formulations was applied to Dusparsakadi Kwatha a formulation for treating Hemorrhoids. The primary study objective of this research is to compute and compare the Drug Efficacy Indices of various possible combinations mentioned in the Classical Texts for treating Hemorrhoids and marketed by modern manufactures under the name Dusparsakadi Kwatha. The linguistic analysis of the corresponding verse of the classical formulation was done using the language interpretation methods based on Paninian concepts. The Drug Efficacy Indices were computed using the earlier reported formula. It is not a clinical study and purely theoretical methods based on the philosophical background of Ayurveda are applied. The computed Drug Efficacy Indices of some of the possible combinations were found more than the marketed formulation. These combinations were successfully practiced by many learned traditional practitioners by adhering to the meaning of the verses of classical texts. The studies successfully computed the efficacies of various combinations. It also showed that the research methodologies must be based on the philosophical background of Alternative Systems of Medicine alone can be successfully applied to their fields.

Synergistic effects of sulbactam in multi-drug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a frequently isolated etiologic agent of nosocomial infections, especially in intensive care units. With the increase in multi-drug resistance of A. baumannii isolates, finding appropriate treatment alternatives for infections caused by these bacteria has become more difficult, and available alternate treatments include the use of older antibiotics such as colistin or a combination of antibiotics. The current study aimed to evaluate the in vitro efficacy of various antibiotic combinations against multi-drug resistant A. baumannii strains. Thirty multi-drug and carbapenem resistant A. baumannii strains isolated at the Ankara Training and Research Hospital between June 2011 and June 2012 were used in the study. Antibiotic susceptibility tests and species-level identification were performed using conventional methods and the VITEK 2 system. The effects of meropenem, ciprofloxacin, amikacin, tigecycline, and colistin alone and in combination with sulbactam against the isolates were studied using Etest (bioMérieux) in Mueller-Hinton agar medium. Fractional inhibitory concentration index (FIC) was used to determine the efficacy of the various combinations. While all combinations showed a predominant indifferent effect, a synergistic effect was also observed in 4 of the 5 combinations. Synergy was demonstrated in 43% of the isolates with the meropenem-sulbactam combination, in 27% of the isolates with tigecycline-sulbactam, and in 17% of the isolates with colistin-sulbactam and amikacin-sulbactam. No synergy was detected with the sulbactam-ciprofloxacin combination and antagonism was detected only in the sulbactam-colistin combination (6.66% of the isolates). Antibiotic combinations can be used as an alternative treatment approach in multi-drug resistant A. baumannii infections.

122 Successful Burkholderia spp. eradication with hypothiocyanite/lactoferrin. In vitro study evidence over a worldwide collection of clinical strains

Objectives To test the efficacy of various combinations of OSCN − and bLF on clinical Burkholderia strains. Methods We tested 165 Burkholderia spp. CF-clinical isolates from worldwide origin. MIC values were obtained according to CLSI guidelines with minor modifications and Time-kill curves with standard methods. All experiments were done in triplicate. Results 100% of isolates tested were inhibited by OSCN − alone within a range of 30–157 mg/mL. In contrast, only 4.8% (8/165) of the tested strains are inhibited by bLF alone within a range of 0.25–96 mg/mL. The FIC analysis of the whole panel of strains reveals that inhibitory combinations are predominantly additive or synergistic for 73% of the collection. The combination of 118 mg/mL of OSCN − with 8 mg/mL of bLF inhibits 100% of tested isolates. Time-kill curves performed on 21 strains. Results show that the OSCN − /bLF combination (ALX-009) decreases the bacterial count by 2–4 logs at 6 h after inoculation when compared to the inoculum and by 4–6 logs if compared to the negative control. 24 h after inoculation, the bacterial counts were reduced by 4–6 logs if compared to the negative control. These results suggest that for time 0–6 h after inoculation OSCN − exerts an important antimicrobial activity that is then maintained by bLF over time. Conclusion The data obtained by Alaxia on 165 clinical isolates of Burkholderia cepacia complex and other Burkholderia spp. demonstrates the high bactericidal potential of the OSCN − /bLF combination (ALX-009) and reinforces both the previous published data and the interest to developing this combination to respond to the unmet medical need of Burkholderia spp. infections in CF patients.

Efficacy of various combinations of irrigants and medicaments on Candida albican: An in vitro study.

Objective:To evaluate the efficacy of 3% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA), calcium hydroxide [Ca (OH)2], and 2% chlorhexidine in various combinations on Candida albicans in root canals for 48 h and 10 days.Materials and Methods:In this in vitro study, 95 extracted teeth were instrumented. MTCC 183 strain of C. albicans was introduced into the root canals and after 7 days, the average value of colony forming units (CFUs)/ml was determined in all the roots. Then the teeth were randomly divided into three groups: Group I (n = 15) was the control group and only saline was added to it. In group II (n = 40), 3% NaOCl was used as the irrigant and in group III (n = 40), 3% NaOCl and 17% EDTA were used as irrigants. Groups II and III were further divided into two subgroups (A and B) having 20 teeth each. After irrigation, Ca (OH)2 was placed in subgroup A and 2% chlorhexidine digluconate (CHX) solution in subgroup B of both groups as intracanal medicament. After 48 h, the CFUs/ml was determined in 45 teeth (5 from the control group and 10 from each subgroup). After 10 days, the CFUs/ml was determined in the remaining 50 teeth (10 from the control group and 10 from each subgroup). For statistical analysis, Statistical Package for Social Sciences (SPSS version 15, Chicago IL, USA) was used.Results:A decrease in CFUs/ml of C. albicans was noted in all subgroups at 48 h, but the combination of NaOCl, EDTA, and CHX (group IIIB) was the most effective showing value of 0.095 × 105 CFUs/ml. On the 10th day, the CFUs/ml of C. albicans was further decreased in all subgroups; but again, subgroup IIIB was the most effective showing a value of 0.025 × 105 CFUs/ml. There was statistically significant difference in CFUs/ml of C. albicans at 48 h and on 10th day in all study groups.Conclusion:The antimicrobial activity of irrigant and intracanal medicament has a positive role in controlling the growth of C. albicans.

Efficacy of semiochemical-baited traps for detection of longhorn beetles (Coleoptera: Cerambycidae) in the Russian Far East

The efficacy of various combinations of pheromones and plant volatile lures for detection of longhorn beetles (Coleoptera: Cerambycidae) in traps was tested in field bioassays in a mixed coniferous-deciduous forest near Vladivostok in the Russian Far East in 2009 and 2010. Traps detected 30 species (490 specimens) in 2009 and 23 species (182 specimens) in 2010. Overall, 38 longhorn beetle species were detected, with 15 species common to both years. Species composition differed among lure treatments, but the number of species detected with any single lure did not vary significantly among lures (12-16 species per lure in 2009; 3-10 species per lure in 2010). Type of lure significantly affected mean catch per trap of five species in 2009 and 2010. For these same species, lure type also significantly affected the efficacy of detection, i.e., the proportion of traps that captured at least one specimen of a given species. The combination of racemic E-fuscumol and spruce blend (a blend of five monoterpenes) positively affected mean catch of Tetropium castaneum (L.). Racemic 3-hydroxyhexan-2-one (K6), alone or combined with ethanol, increased mean catch of Anaglyptus colobotheoides Bates. The combination of K6 and ethanol increased mean catch of Phymatodes testaceus (L.), and the combination of racemic 3-hydroxyoctan-2-one and ethanol increased mean catch of Molorchus minor (L.). Use of longhorn beetle pheromone lures in trapping surveys increases the mean catch and probability of detecting certain species of Cerambycidae, including those that may be exotic and potentially invasive. Sample-based rarefaction indicated that eight traps per site were insufficient to detect all of the longhorn species potentially attracted by any individual lure treatment, i.e., species accumulation curves failed to reach an asymptote in most cases.

MMP-2/9-oriented combinations enhance antitumor efficacy of EGFR/HER2-targeting fusion proteins and gemcitabine.

To increase the antitumor efficacy, in the present study, we proposed several settings of matrix metalloproteinase (MMP)-2/9-oriented combinations that comprise the MMP-2/9-targeting fusion protein dFv-LDP and the MMP inhibitor doxycycline (DOX) in association with EGFR/HER2-bispecific fusion protein Ec-LDP-Hr, its enediyne-energized analogue Ec-LDP-Hr-AE, and gemcitabine (GEM). The expressions of various fusion proteins were detected by western blot analysis. Proliferation and migration inhibition of cells were determined by MTT and Transwell assay, respectively. The binding capability of dFv-LDP and Ec-LDP-Hr to cancer cells was examined by ELISA, cell immunofluorescence coimmunoprecipitation and confocal assays. Animal experiments were set to investigate the antitumor efficacy of various combinations against colorectal carcinoma HCT-15 xenograft in athymic mice. These two targeting proteins dFv-LDP and Ec-LDP-Hr had strong binding capabilities and antiproliferation effects on various cancer cell lines. Enhanced therapeutic efficacy in vivo was observed in the MMP-2/9-targeting fusion protein dFv-LDP integrated combinations including: i) dFv-LDP and Ec-LDP-Hr, ii) dFv-LDP and enediyne-energized fusion protein Ec-LDP-Hr-AE, iii) dFv-LDP and Ec-LDP-Hr-AE plus DOX, and iv) dFv-LDP and GEM plus DOX against colorectal cancer HCT-15 xenograft in athymic mice. In setting iii, DOX (20 mg/kg), dFv-LDP (20 mg/kg) and Ec-LDP-Hr-AE (0.3 mg/kg) alone suppressed tumor growth by 35, 49.7 and 67.5%, respectively. The combination of dFv-LDP and Ec-LDP-Hr-AE was 75.1%. Furthermore, this combination plus DOX showed stronger efficacy with an inhibitory rate of 82.7%. In setting iv, the combination of dFv-LDP and GEM suppressed tumor growth by 66.3%. Notably, the tumor inhibitory rate of the dFv-LDP/GEM/DOX combination reached 85.5%, producing initial shrinkage after the first administration. The MMP-2/9-oriented combination strategy that employs the MMP-2/9-targeting antibody-based fusion protein and the small molecular inhibitor DOX as the basic composed agents may enhance antitumor efficacy in association with the EGFR/HER2-targeting fusion protein and GEM. This multiple targeting approach may be useful for enhancing antitumor efficacy against colorectal cancer.

Testing the degradation effects of three reagents on various antineoplastic compounds.

Studies for decontamination of antineoplastic compounds have been conducted for decades. Nevertheless, recent studies indicate the contamination of work place in hospitals, and the exposure of workers. In this study, to develop an effective cleaning method for contaminated environments, the degradation efficacies of antineoplastic compounds by reagents were evaluated. The degradation efficacies of various combinations of three reagents (sodium hypochlorite, sodium thiosulfate, and sodium hydroxide) were evaluated with four antineoplastic compounds (cyclophosphamide, epirubicin, cisplatin, and carboplatin). The residues of antineoplastic compounds were measured with high-performance liquid chromatography. Of the three reagents, sodium hypochlorite was the most effective to all antineoplastic compounds used in this study. Although sodium hypochlorite degraded 86.6% of cyclophosphamide, it degraded other three antineoplastic compounds completely. The combination with sodium hypochlorite and sodium thiosulfate degraded only 3.3% of cyclophosphamide, since sodium thiosulfate inhibited the degradation ability of sodium hypochlorite. Similarly, the combinations used in all three reagents failed to degrade cyclophosphamide. Although three of four antineoplastic compounds were degraded successfully, any combinations of three reagents could not degrade cyclophosphamide completely. However, the addition of sodium thiosulfate which inhibits the corrosion of metal by sodium hypochlorite is essential for daily cleaning. Therefore, the evaluation of reaction time before the addition of sodium thiosulfate may be required. We will continue to investigate the reagents for degradation.