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Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.

The potential impacts of climate change on human health in sub-Saharan Africa are wide-ranging, complex, and largely adverse. The region's Indigenous peoples are considered to be at heightened risk given their relatively poor health outcomes, marginal social status, and resource-based livelihoods; however, little attention has been given to these most vulnerable of the vulnerable. This paper contributes to addressing this gap by taking a bottom-up approach to assessing health vulnerabilities to climate change in two Batwa Pygmy communities in rural Uganda. Rapid Rural Appraisal and PhotoVoice field methods complemented by qualitative data analysis were used to identify key climate-sensitive, community-identified health outcomes, describe determinants of sensitivity at multiple scales, and characterize adaptive capacity of Batwa health systems. The findings stress the importance of human drivers of vulnerability and adaptive capacity and the need to address social determinants of health in order to reduce the potential disease burden of climate change.

Policymakers at global level recognise that household biomass use in developing countries has significant health consequences. However, it is unclear how local-level health professionals perceive and respond to such health effects. This paper which is derived from the findings of a larger study on perceptions and responses to the harmful health effects of carrying heavy firewood loads and to smoke from cooking fires is based on a study conducted in South Africa among managers of health programmes and community nurses of Qaukeni and Mhlontlo municipalities in rural Eastern Cape. Interviews and participant observations were conducted in 2009 using ethnographic grounded theory approaches. In addition to a 10-month period of ethnographic fieldwork, ten programme managers and nurses in two villages were interviewed about health patterns in the villages that they serve, their perceptions of, and responses to the health effects of carrying heavy firewood loads, and inhalation of smoke from wood and dung cooking fires, their professional qualifications and experience, their own household energy use; and observations made as they served clinic clients. Results show that these programme managers and nurses perceive the health effects of carrying heavy loads of firewood and of cooking smoke as minor. Sometimes, nurses give women symptomatic relief for musculoskeletal pain resulting from carrying heavy loads. We posit that their perceptions are derived from customary neglect of work-related health and non-communicable diseases, cultural interpretations of womanhood, limited access to relevant information, and limited interactions between health and energy sector professionals. We conclude that culturally and gender-sensitive awareness programmes are needed for local-level health professionals to effectively address health effects of biomass collection and use. This paper provides new insights into overlooked differences between globally-driven initiatives to address health effects of biomass use and local perceptions.

Gender-related differences in the pharmacological effects of addictive drug are an emerging issue. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of alcohol and cocaine intake since they cause complex pharmacological interactions, not least the formation of the active metabolite cocaethylene.The MEDLINE database was searched from 1990 to 2014 in order to find articles related to gender differences in alcohol, cocaine and cocaethylene pharmacokinetics and pharmacodynamics.Besides the well known gender differences in alcohol pharmacokinetics, women appear more susceptible to alcohol-mediated brain damage and seem to suffer more than men the acute effects of alcohol on hepatic and gonadal hormones. No significant gender differences have been found in the pharmacokinetics of cocaine taken alone; yet, in women pharmacological sensitivity to the drug seems to vary in relation to menstrual cycle; moreover, progesterone attenuates subjective effects of cocaine in women. Higher ratings at a subjective measure of mental/physical well-being have been observed in women when given cocaine and alcohol, alone or in combination. Finally, among subjects dependent on both alcohol and cocaine, men only benefit from naltrexone, whereas women used more cocaine during the trial and were less compliant to therapy than men.The observed subtle gender differences in the pharmacokinetics and pharmacodynamics of both alcohol and cocaine may have no subtle influence on the natural history of the co-abuse of the two drugs by women.

Blunt force injuries are produced by a variety of objects, including hands and feet (which is human strength) and many different weapons. Some of these objects produce distinctive patterns of injury of potential evidentiary value. This article presents a series of 53 homicides by blunt trauma along the period from 1982 to 2012, representing 16% of all homicides treated by the University Institute of Forensic Medicine in Brescia (northern Italy). Fifty-seven percent (30 cases) of the victims were male. The mean age of the victims was 47.9 years. The weapon most frequently involved was human strength. Not surprisingly, head trauma was the most common cause of death (66%). Forty-seven percent (25 cases) of the victims survived their assaults for varying periods. Homicides due to blunt trauma are still a relevant challenge for the forensic pathologist, who must obtain a complete and accurate history of the crime (including details regarding the crime scene), interpret patterns of injury and other findings at autopsy, and correlate all of the findings to make an accurate ruling of the cause and manner of death.

AbstractBackground: Chlorhexidine (CHX) 0.2% solution is still “the leading oral antiseptic” for controlling gingivitis. Side effects, however, limit the acceptability to users and the long‐term employment of a 0.2% CHX antiseptic in preventive dentistry. This stimulated the development of new formulations. The aim of the present study was to assess the effect on plaque inhibition and taste perception of two commercially available mouthrinses (0.12% CHX non‐alcohol base with 0.05% cetyl pyridinium chloride (Cpc) versus 0.2% CHX alcohol base).Methods: The study was designed as a single‐blind, randomized two group parallel experiment, to compare two different commercially available mouthrinses, during a 3‐day plaque accumulation model. Forty healthy volunteers were enrolled in the study and received a thorough dental prophylaxis at the beginning of the test period. Over a 72‐h experimental non‐brushing period, during which subjects abstained from all forms of mechanical oral hygiene, one group (test) used a 15 ml alcohol free 0.12% CHX (=18 mg) mouthrinse on a Cpc base (Perioaid®, CHX⊕Cpc), twice daily for 30 s. The other group (control) used a 10 ml 0.2% CHX (=20 mg) mouthrinse on an 11.8% ethanol alcohol base (Corsodyl®, CHX⊕Alc), twice daily for 60 s. After 72 h of plaque formation, the amount of plaque was evaluated. By the use of visual analogue scale, the subjects were asked for their appreciation of the taste of the mouthrinse they had used.Results: The mean plaque index for the CHX⊕Cpc group was 0.97 and for the CHX⊕Alc group 0.78. After 72 h of non‐brushing, there was no significant difference in plaque accumulation between the two groups. The answers to the questions (taste perception and after‐taste) showed a statistically significant difference between the two groups. The mean visual analogue scale (VAS) scores for taste appreciation on a scale from very bad to very good taste (0–10) were 5.92 for the CHX⊕Cpc group and 4.10 for the CHX⊕Alc group (p=0.02). The mean visual analogue scale (VAS) scores for the after‐taste on a scale from very short to very long (0–10) were 7.24 for the CHX⊕Cpc group and 5.38 for the CHX⊕Alc group.Conclusions: Within the limitations of the present study design, it can be concluded that rinsing with a 0.12% CHX mouthrinse on a non‐alcohol base with 0.05% Cpc (Perio‐Aid®) is not significantly different from rinsing with a 0.2% CHX mouthrinse on an alcohol base (Corsodyl®). It appears that the subjects appreciated the taste of the non‐alcohol CHX solution better but the after‐taste of the rinse remained longer in the mouth.

Marine mammals accumulate alarming amounts of environmental pollutants and are thus the most contaminated group of animals in the world. Elevated pollutant exposure is of concern to marine mammals because of potential adverse effects on reproduction, endocrine disruption and immunity. In vitro techniques can be used to assess effects on specific health endpoints. To date, however, most studies focus on single compound exposures, rather than realistic complex mixtures, and little has been done to extrapolate molecular effects to higher levels of biological organization. The aim of my PhD was to use a unique combination of approaches, namely statistical meta-analyses, in vitro experimentation, analytical chemistry, and ecological modeling, to gain further insight into pollutant accumulation and effects at molecular and organism levels in North-Atlantic top predators.

Historically, the roots of alcoholism have been linked to either environment or heredity. However, the interaction between these factors is still largely unexplored. The evidence supports a link between alcohol consumption and the endogenous opioid system. We here studied the opioid genes expression in male and female Wistar rats derived from a short-term breeding program which selected -- at adolescence -- for high (ADHI line) or low (ADLO line) ethanol drinking. Specifically, in this work we analyzed central opioid gene expression in the rats of the second filial generation (S2-ADLO and S2-ADHI). Selective downregulation of pronociceptin (Pnoc) and its receptor (Oprl1) mRNA levels were observed in the prefrontal cortex of male S2-ADHI rats when compared to S2-ADLO, and for Oprl1 also in the nucleus accumbens. An increase in gene expression was instead observed for pro-opiomelanocortin (Pomc) in the nucleus accumbens of S2-ADHI males when compared to S2-ADLO, as well as for mu opioid receptor (Oprm1) but in females. The differences in mRNA levels may be due to the different alcohol consumption between the two groups of rats or may represent pre-existing differences between them. Moreover, we show a sex-specific modulation of the expression of these genes, thus pointing out the importance of sex on ethanol responses. The results might lead to more specific and effective pharmacological treatments for alcoholism.