Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken.     

A school-based oral health educational program: the experience of Maringa- PR, Brazil

The main purpose of this study was to evaluate the preliminary results of a school-based oral health educational strategy adopted in public primary schools from the city of Maringa, State of Parana, Brazil. The study sample was composed by 556 children and adolescents aged 6 to 17 years old, 124 schoolteachers and a group of 55 mothers. The educational approach was implemented for 18 months and consisted of reinforcements of interventions addressed to students and schoolteachers at school level and few activities targeted at the mothers, performed by means of home visits. Baseline and follow-up interviews focused on oral health care were undertaken for the entire study population. As a stimulus for the students to achieve proper oral hygiene habits, the simplified oral hygiene index was assessed at three different moments. A statistically significant improvement in their oral hygiene index (p<0.001) was recorded. The results achieved suggest an encouraging tendency towards the improvement in the levels of oral health care among the school-age youths studied. They also point out the need of intensifying the preparation of schoolteachers in oral health topics, as well the instructions to the mothers for their oral health care. Moreover, they highlight the importance of the continuous implementation of school-based programs to promote the oral health.     

AT–1001: a high-affinity α3β4 nAChR ligand with novel nicotine-suppressive pharmacology

Background and Purpose

The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001.

Experimental Approach

Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.

Key Results

AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm.

Conclusions and Implications

These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications.     

Transcranial direct current stimulation in psychiatric disorders

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.     

Quantification of hormonal changes by effects of hippotherapy in the autistic population

Zootherapy, more specifically in its equine form, has proliferated recently as a therapeutic activity and is one of the most common applications in the stimulation of autistic individuals. At the same time, the influence of certain hormones was recently revealed in the behavior of autistic spectrum disorders. We propose to objectify the influence of analyzing equestrian therapies through laboratory methods and non-invasive techniques (salivary samples), in the hormone levels of cortisol and progesterone, thus indirectly those of oxytocin, before and after hippotherapy sessions for people with Autism Spectrum Disorder (ASD). The main results indicated that equine therapy decreased (p ?? 0.05) the levels of salivary Cortisol in the rest of the sessions (before Hippotherapy 33.11 ± 0.96 ng/mL vs. after Hippotherapy 2.23 ± 0.75 ng/mL). And also the levels of salivary progesterone in the first session (before Hippotherapy 28.63 ± 12.81 ng/mL vs. after Hippotherapy 51.59 ± 33.11 ng/mL) and in the rest of the sessions (before hippotherapy 21.58 ± 12 pg/mL vs. after Hippotherapy 26.03 ± 11.98 pg/mL) which was always on the rise. These effective results were corroborated with the Cortisol/Progesterone Balance which reduced after equine therapy in the first session (before Hippotherapy 99.87 vs. after Hippotherapy 76.24) and the other sessions (before Hippotherapy 181.31 vs. after Hippotherapy 110.48). In conclusion, the Hippotherapy sessions for the population with ASD generated leads to an improvement in social attitudes, and it is confirmed with the effective modulation of the implicating hormones.     

Carboplatin delays mammary cancer 4T1 growth in mice

Carboplatin is commonly used to treat a variety of tumors. We investigated the effects of carboplatin (100 mg/kg) in the development and metastatic dissemination of the 4T1 mice mammary carcinoma. Carboplatin was able to reduce tumor volume and the number of lung metastases in 50% compared to the control animals. Mitotic and apoptotic indices were also decreased by the treatment. Assessment of the vascularization of the tumors revealed a significant decrease in blood vessel formation by carboplatin. A decrease in nuclear positivity of CDC47 and cyclin D1 was observed in the group treated with carboplatin when compared to the control group. Positivity for p53 was observed in the control group (2/28; 5%) and the treated group (5/71; 4%). Carboplatin has been demonstrated to be an efficient regulator of 4T1MMT growth and dissemination. The action of this chemotherapeutic agent seems to be related to the induction of apoptosis and inhibition of angiogenesis and cell proliferation.     

Chronic Silymarin,Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats

Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.