Long-term effects of alcohol-avoidance training: Do changes in approach bias predict who will remain abstinent?

Background: Patients with alcohol use disorder (AUD) tend to selectively approach alcohol cues in the environment, demonstrating an alcohol-approach bias. Alcohol-approach-bias modification (Alcohol-ApBM) effectively increases abstinence rates in patients with AUD when added to abstinence-focused treatment, but the evidence for its proposed working mechanism (reduction of the alcohol-approach bias) is limited. Moreover, not all patients benefit from Alcohol-ApBM, and previous research did not identify reliable pretreatment predictors of Alcohol-ApBM effectiveness.

Implementing Approach-Bias Modification as Add-On to Varieties of Clinical Treatment for Alcohol Use Disorders: Results of a Multicenter RCT.

Introduction: Abstinence rates after inpatient treatment for alcohol use disorder (AUD) are modest (1-year rate around 50%). One promising approach is to re-train the automatically activated action tendency to approach alcohol-related stimuli (alcohol-approach bias) in AUD patients, as add-on to regular treatment. As efficacy has been demonstrated in well-controlled randomized controlled trials, the important next step is to add alcohol-approach-bias modification (alcohol-ApBM) to varieties of existing treatments for AUD.

Does selective inhibition training reduce relapse rates when added to standard treatment of alcohol use disorder? A randomized controlled trial.

Background: Alcohol-dependent individuals tend to selectively approach alcohol cues in the environment, demonstrating an alcohol approach bias. Because approach bias modification (ApBM) training can reduce the approach bias and decrease relapse rates in alcohol-dependent patients when added to abstinence-focused treatment, it has become a part of regular treatment. Moreover, in selective inhibition (SI) training, responses to one category of stimuli (i.

Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure-activity relationship, toxicity, and mechanism of action.

Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T.

Chemical Constituents and Pharmacology properties of Aristolochia triangularis: a south brazilian highly-consumed botanical with multiple bioactivities.

Aristolochia triangularis Cham., is one of the most frequently used medicinal plant in Southern Brazil. Preparations containing the leaves and/or stems are traditionally used as anti-inflammatory, diuretic, as well as antidote against snakebites.

Biological activities of marine invertebrates extracts from the northeast brazilian coast.

This paper reports the in vitro antiproliferative effects, antiprotozoal, anti-herpes and antimicrobial activities of 32 organic extracts of 14 marine sponges and 14 corals collected in northeast Brazilian coast. The ethanolic extracts of the sponges Amphimedon compressa and Tedania ignis, and the acetone extract of Dysidea sp. showed relevant results concerning the antiproliferative effects against A549, HCT-8, and PC-3 cell lines by sulforhodamine B assay, but also low specificity.

Clerodane Diterpenes from the Marine Sponge Collected in South Brazil.

The marine sponge , collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge's hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (), isolated from a sponge of the same genus collected in New Zealand.

TSH fraction from Petromica citrina: A potential marine natural product for the treatment of sepsis by Methicillin-resistant Staphylococcus aureus (MRSA).

Background And Purpose: Antibiotic resistance is now a worldwide public health problem. A potential alternative source in the search for new antibiotics is the bioactive molecules obtained from marine products, as the halistanol trisulfate, obtained from Petromica citrina, and herein investigated from its antimicrobial and anti-inflammatory properties.

Experimental Approach: The antimicrobial activity of the fractionation products (TSH fraction, halistanol sulfate (HS) and halistanol sulfate C (HS-C)) of the marine sponge Petromica citrina was evaluated against twenty bacteria and two fungi strains by the disk diffusion and microdilution methods.

Synthesis and biological evaluation of isoxazolyl-sulfonamides: A non-cytotoxic scaffold active against Trypanosoma cruzi, Leishmania amazonensis and Herpes Simplex Virus.

In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed low cytotoxicity and were promising regarding all other biological activities reported herein, especially the inhibitory activity against T.

Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity.

Despite the impressive scientific and technological advances of recent decades, no effective treatment is currently available for Chagas disease. Our research group has been studying the design and synthesis of analogues of natural lignans aiming to identify compounds with antiparasitic activity. This article reports the synthesis of 42 novel bis-heterocyclic derivatives and the structure-activity relationship study conducted based on results of biological assays against Trypanosoma cruzi amastigotes.

Effects of nasal dilator strips on subjective measures of sleep in subjects with chronic nocturnal nasal congestion: a randomized, placebo-controlled trial.

Background: This exploratory study investigated effects of a new asymmetric butterfly-shaped prototype nasal dilator strip and the currently marketed clear Breathe Right Nasal Strip (BRNS) on subjective measures of nasal congestion and sleep quality.

Methods: In this randomized, double-blind study, subjects with chronic nasal congestion and sleep difficulties were assigned a BRNS clear strip, an asymmetric butterfly prototype, or an asymmetric butterfly placebo strip without springs, to use nightly for 2 weeks. The main outcomes included change from baseline to days 7 and 14 on the Pittsburgh Insomnia Rating Scale (PIRS), Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ), and Congestion Quantifier Seven-Item Test (CQ7).

The sedative activity of flavonoids from Passiflora quadrangularis is mediated through the GABAergic pathway.

The aim of this study was to investigate the sedative activity of the aqueous leaf extract of Passiflora quadrangularis, a species that is widely cultivated and consumed in South America, and to identify its main constituents and elucidate the involvement of the GABAergic pathway in its mechanism of action. The bioguided fractionation of the crude extract showed a positive relationship between the sedative activity of the extract and its flavonoids. The methods employed to identify and isolate its main flavonoids resulted in the identification of vitexin-2''-O-xyloside, vitexin-2''-O-glucoside, orientin-2''-O-xyloside and orientin-2''-O-glucoside.

Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells.

Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis.

Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1) and veraguensin (2) show activity against trypomastigote T.

Impact of sodium chloride on the expansion of a liquid-liquid miscibility gap in an API/water system. Case study of Brivaracetam.

Brivaracetam, or (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl] butanamide, is an active pharmaceutical ingredient designed for the treatment of epilepsy. During the development of the IV administration mode, a liquid-liquid miscibility gap has been observed with pure water, isotonic and hypertonic solutions (vehicle at 0.9% w/w and 5%w/w NaCl respectively).

Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549.

Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells).

Feasibility study with 99mTc-HYNIC-βAla-Bombesin(7-14) as an agent to early visualization of lung tumour cells in nude mice.

Aim: More sensitive and accurate imaging approaches for early detection and therapy monitoring of lung tumours are needed to ameliorate prognosis and outcome. Lung tumours are known to overexpress receptors for bombesin-like peptides. However, thus far, no study has demonstrated the potential role of bombesin-like peptides in identifying A549 lung tumour cells in xenograft animal models.

Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells.

Development and validation of a method for the analysis of hydroxyzine hydrochloride in extracellular solution used in in vitro preclinical safety studies.

In the process of drug development, preclinical safety studies are to be performed that require the analysis of the compound at very low concentrations with high demands on the performance of the analytical methods. In the current study, a UPLC-MS/MS method was developed and validated to quantify hydroxyzine hydrochloride in an extracellular solution used in a hERG assay in concentrations ranging from 0.01 to 10μM (4.

Ilex paraguariensis Pellets from a Spray-Dried Extract: Development, Characterization, and Stability.

Several studies have shown the potential use of Ilex paraguariensis in developing products with the aim to protect biological systems against oxidative stress-mediated damages. In the same way, technological studies have demonstrated the feasibility of obtaining dry products, by spray-drying process, from aqueous extracts of I. paraguariensis in laboratory.

Isolation of C-glycosylflavonoids with α-glucosidase inhibitory activity from Passiflora bogotensis Benth by gradient high-speed counter-current chromatography.

In this study, we applied a gradient High-Speed Counter-Current Chromatography (HSCCC) method that allowed, by direct injection of an aqueous crude extract of the leaves of Passiflora bogotensis, the successful isolation of six flavonoids in a single run, with purity of each compound higher than 81%. This separation enabled the isolation of two new flavonoid glycosides, apigenin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-β-d-glucopyranoside (2) and luteolin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-β-d-glucopyranoside (4), and four known ones, isovitexin (1), isoorientin (3), isovitexin-2″-O-rhamnoside (5) and isoorientin-2″-O-rhamnoside (6). The structures of the isolated compounds were identified by HPLC-DAD, LC-MS, (1)H and (13)C NMR and comparison with literature data.

Anxiolytic-like, stimulant and neuroprotective effects of Ilex paraguariensis extracts in mice.

Yerba-mate (Ilex paraguariensis St. Hil.) is the most used beverage in Latin America with approximately 426 thousand of tons consumed per year.

In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B.

Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation.

Polyoxygenated steroids from the octocoral Leptogorgia punicea and in vitro evaluation of their cytotoxic activity.

Five new polyoxygenated marine steroids-punicinols A-E (1-5)-were isolated from the gorgonian Leptogorgia punicea and characterized by spectroscopic methods (IR, MS, 1H, 13C and 2-D NMR). The five compounds induced in vitro cytotoxic effects against lung cancer A549 cells, while punicinols A and B were the most active, with IC50 values of 9.7 μM and 9.

Glycosylflavonoids from Cecropia pachystachya Trécul are quorum sensing inhibitors.

The Cecropia genus is widely distributed in Latin America including at least 60 species, and some of them are commonly used in traditional medicine for the treatment of several diseases. We used Cecropia pachystachya Trécul to search for quorum sensing (QS) inhibitors compounds and found that the aqueous extract of C. pachystachya leaves is a promising source of substances with this activity.