Search results for "Combination"

Rbt1 Protein Domains Analysis in Candida albicans Brings Insights into Hyphal Surface Modifications and Rbt1 Potential Role during Adhesion and Biofi…

2013

Cell wall proteins are central to the virulence of Candida albicans. Hwp1, Hwp2 and Rbt1 form a family of hypha-associated cell surface proteins. Hwp1 and Hwp2 have been involved in adhesion and other virulence traits but Rbt1 is still poorly characterized. To assess the role of Rbt1 in the interaction of C. albicans with biotic and abiotic surfaces independently of its morphological state, heterologous expression and promoter swap strategies were applied. The N-terminal domain with features typical of the Flo11 superfamily was found to be essential for adhesiveness to polystyrene through an increase in cell surface hydrophobicity. A 42 amino acid-long domain localized in the central part o…

Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression.

2008

Background & Aims Foxp3-expressing regulatory T cells (Tregs) play a key role in the maintenance of the gut immune homeostasis, and an intact transforming growth factor (TGF)-β signaling is required for their function. In inflammatory bowel disease (IBD), the TGF-β signaling is impaired because of high expression of the inhibitory molecule Smad7. Although no intrinsic defects in Tregs function have been shown in IBD, it is still unknown whether colitogenic T cells are susceptible to Treg-mediated suppression. In this study, we have investigated whether IBD mucosal CD4+ T cells are resistant to Tregs and whether Smad7 is involved in this process. Methods IBD lamina propria mononuclear cells …

Retinal Vibrations in Bacteriorhodopsin are Mechanically Harmonic but Electrically Anharmonic: Evidence From Overtone and Combination Bands

2021

Fundamental vibrations of the chromophore in the membrane protein bacteriorhodopsin (BR), a protonated Schiff base retinal, have been studied for decades, both by resonance Raman and by infrared (IR) difference spectroscopy. Such studies started comparing vibrational changes between the initial BR state (all-trans retinal) and the K intermediate (13-cis retinal), being later extended to the rest of intermediates. They contributed to our understanding of the proton-pumping mechanism of BR by exploiting the sensitivity of fundamental vibrational transitions of the retinal to its conformation. Here, we report on new bands in the 2,500 to 1,800 cm−1 region of the K-BR difference FT-IR spectrum.…

Bempedoic acid as adjunct for traditional lipid-lowering therapy in patients with hyperlipidaemia

2020

Statin therapy has been the cornerstone for the reduction of cholesterol and circulating low-density lipoprotein (LDL) in patients with cardiovascular diseases. However, statin monotherapy has disadvantages attributable to myopathies and to the insufficient cholesterol reduction observed in some patients. There is a need for new well-tolerated therapies for lowering LDL. This review will focus on bempedoic acid in combination with traditional statin therapy or other lipid-lowering agents and its emerging role in LDL-C lowering. Bempedoic acid is also a viable alternative for reducing LDL cholesterol in the treatment of some patients suffering from heterozygous familial hypercholesterolemia.

Paediatric solid oral dosage forms for combination products: Improving in vitro swallowability of minitablets using binary mixtures with pellets

2023

There is a growing interest in determining and improving the acceptability of solid oral dosage forms (SODF) in paediatric populations. Combination products can be an interesting solution to combine two active pharmaceutical ingredients. This study shows that binary mixture of paediatric SODF could enhance formulation swallowability and palatability. Using the Paediatric Soft Robotic Tongue (PSRT) – an in vitro device inspired by the anatomy and physiology of 2-year-old children – we investigated the oral phase of swallowing of multi-particulate formulations, i.e., pellets (350 and 700 µm particles), minitablets (MTs, 1.8 mm), and their binary mixtures (BM), by measuring the oral swallowing…

Combination therapy in a model of pulmonary aspergillosis

2009

Summary. The current treatment for pulmonary aspergillosis, amphotericin B, is toxic and not always effective. This study was done to evaluate combinations of amphotericin B with other agents in an animal model of pulmonary aspergillosis. Sprague-Dawley rats were treated with cortisone acetate, infected intratracheally with 106 spores of Aspergillus fumigatus, and followed daily for survival. Mortality among controls started on day 2, and it was 80% by day seven, whereas therapy with amphotericin B resulted in survival of all animals. When given alone, ketoconazole, 5-fluorocytosine and rifampin did not improve survival. The combination of ketoconazole with amphotericin B resulted in comple…

Drivers of topoisomerase II poisoning mimic and complement cytotoxicity in AML cells

2019

Recently approved cancer drugs remain out-of-reach to most patients due to prohibitive costs and only few produce clinically meaningful benefits. An untapped alternative is to enhance the efficacy and safety of existing cancer drugs. We hypothesized that the response to topoisomerase II poisons, a very successful group of cancer drugs, can be improved by considering treatment-associated transcript levels. To this end, we analyzed transcriptomes from Acute Myeloid Leukemia (AML) cell lines treated with the topoisomerase II poison etoposide. Using complementary criteria of co-regulation within networks and of essentiality for cell survival, we identified and functionally confirmed 11 druggabl…

Polymer-drug conjugates as platforms for combination therapy in the treatment of hormone-dependent breast cancer

2013

1. Objetivos de la Investigación. Los conjugados poliméricos son nanoconstrucciones multicomponente presentes actualmente en clínica como terapia anticancerígena, tanto como agentes únicos, como formando parte de combinaciones. Estos nanoconjugados tienen el potencial de mejorar farmacológicamente el tratamiento de tumores sólidos, debido a una acumulación pasiva en el tumor (efecto ‘EPR’) y a un diferente mecanismo de internalización celular y posterior liberación del fármaco(s). La transferencia de conjugados polímero-proteína a uso clínico rutinario, y el desarrollo clínico de conjugados polímero-fármaco anticancerígeno sitúa a los conjugados poliméricos como una de las primeras clases d…

Corresponding doses of mometasone furoate (MF) in once-daily inhaled fixed-dose combination (FDC) of indacaterol/mometasone furoate (IND/MF) and inda…

2021

On the Stability of Stablecoins

2021

This paper investigates the volatility processes of stablecoins and their potential stochastic interdependencies with Bitcoin volatility. We employ a novel approach to choose the optimal combination for the power law exponent and the minimum value for the volatilities bending the power law. Our results indicate that Bitcoin volatility is well-behaved in a statistical sense with a finite theoretical variance. Surprisingly, the volatilities of stablecoins are statistically unstable and contemporaneously respond to Bitcoin volatility. Also, whereas the volatilities of stablecoins are not Granger-causal for Bitcoin volatility, lagged Bitcoin volatility exhibits Granger-causal effects on the vol…