Carbamazepine, venlafaxine, tramadol, and their main metabolites: Toxicological effects on zebrafish embryos and larvae.

Pharmaceutical compounds and their metabolites are found in natural and wastewater. However, investigation of their toxic effects on aquatic animals has been neglected, especially for metabolites. This work investigated the effects of the main metabolites of carbamazepine, venlafaxine and tramadol. Zebrafish embryos were exposed (0.1-100 µg/L) for 168hpf exposures to each metabolite (carbamazepine-10,11-epoxide, 10,11-dihydrocarbamazepine, O-desmethylvenlafaxine, N-desmethylvenlafaxine, O-desmethyltramadol, N-desmethyltramadol) or the parental compound. A concentration-response relationship was found for the effects of some embryonic malformations. Carbamazepine-10,11-epoxide, O-desmethylvenlafaxine and tramadol elicited the highest malformation rates. All compounds significantly decreased larvae responses on a sensorimotor assay compared to controls. Altered expression was found for most of the 32 tested genes. In particular, abcc1, abcc2, abcg2a, nrf2, pparg and raraa were found to be affected by all three drug groups. For each group, the modelled expression patterns showed differences in expression between parental compounds and metabolites. Potential biomarkers of exposure were identified for the venlafaxine and carbamazepine groups. These results are worrying, indicating that such contamination in aquatic systems may put natural populations at significant risk. Furthermore, metabolites represent a real risk that needs more scrutinising by the scientific community.

Norfluoxetine and venlafaxine in zebrafish larvae: Single and combined toxicity of two pharmaceutical products relevant for risk assessment.

Antidepressant metabolites are found in natural and waste waters. However, investigation of their toxic effects on aquatic animals, single or in mixture with other occurring psychoactive drugs, has been neglected. Here, effects of 80hpf exposure to norfluoxetine (0.64-400 ng/L), venlafaxine (16-10000 ng/L) or their combination (3.2 ng/L +2000 ng/L, respectively) were investigated in embryos and zebrafish larvae. Mortality, embryonic malformations, sensorymotor reflexes and the expression of 34 genes involved in the toxicants mode-of-action (MoA) and metabolism were evaluated (i.e. monoamine receptors and transporters, nuclear receptors, and detoxification transporters and enzymes). Compared to controls, norfluoxetine treatments only caused depigmentation of embryos and larvae. Venlafaxine-exposed larvae exhibited depigmentation and spinal deformities, impaired sensorymotor reflexes, alterations in the expression of genes belonging to the serotonergic, noradrenergic and dopaminergic pathways, as well as nuclear receptors related to lipid and drug metabolism. The mixture elicited distinct interaction effects, depending on the level of biological organisation analysed and the neurotransmitter pathways affected; synergism (lethality), no interaction (sensorymotor reflexes), antagonism and inverse agonism (gene expression). The results call for investigation of the toxicity of pharmaceutical metabolites single and in mixture, as well as their risk assessment in approaches accounting for possible interactions with other endocrine-disrupting compounds.

The role of microsurgical flaps in primary burn reconstruction.

Despite the wide and growing use of microsurgery, its application in primary burn reconstruction is not very frequent as it faces a number of additional challenges in this setting. A retrospective analysis of the clinical records of all patients submitted to microvascular free tissue transfer for primary burn reconstruction over an 8-year period (from January 2009 to December 2016) was performed. An evaluation of the indications, timing, principles of flap selection, complications and outcomes of free tissue transfer in primary burn reconstruction was made. Fourteen patients required 18 microsurgical flaps for acute soft tissue reconstruction (1.1% of all patients admitted). 64.3% of the patients were male. The mean age was 59.64 years, and mean TBSA was 10.5%. The majority of the injuries were caused by flames (71.4%), followed by electrical contact (21.4%). The primary indication for microsurgical reconstruction was tissue deficit with exposure of tendons, nerves, vessels, bone and/or joints after debridement. The procedure was more often performed in the early period after injury (between the 5th and 22nd day). The most frequently used flaps were the Latissimus dorsi and the anterolateral thigh flap. Major complications included 2 total flap failures (11.1%) and a partial flap failure that required reconstruction with another free flap. Microsurgical free flaps have a valuable role in primary burn reconstruction. Despite the reported higher complication rate in this specific clinical scenario, their use may reduce the total number of surgeries needed to achieve wound closure.

Bien que de plus en plus utilisée, la microchirurgie est rarement utilisée dans la prise en charge initiale des brûlés, et doit faire face à plusieurs difficultés supplémentaires dans cette indication. Nous avons effectué une analyse rétrospective des dossiers de tous les patients brûlés entre janvier 2009 et décembre 2016 ayant bénéficié au stade d'un lambeau libre (LL). Nous avons évalué l'indication, le délai, la sélection du site donneur, les complications et l'évolution du lambeau. Quatorze patients (1,1% du total) dont 64,5% d'hommes ont bénéficié de 18 LL. L'âge moyen était de 59,64 ans, la surface brûlée de 10,5%. La majorité des brûlures (71,4%) étaient dues à une flamme, 21,4% à l'électricité. L'indication principale était l'exposition ostéo-articulaire ou d'éléments nobles (tendons, nerfs, vaisseaux) après excision. La réalisation du LL était précoce (J5-J22). Les sites donneurs étaient Latissimus dorsi et la région antéro-latérale de cuisse. Deux lambeaux ont totalement nécrosé, un partiellement, ce qui a nécessité la réalisation d'un second LL. Les LL ont une place dans la prise en charge initiale des brûlés. Bien de grevés d'un taux de complications plus élevé dans cette indication, ils peuvent permettre de diminuer le nombre d'interventions nécessaires à la cicatrisation.

The last frontier: Coupling technological developments with scientific challenges to improve hazard assessment of deep-sea mining.

The growing economic interest in the exploitation of mineral resources on deep-ocean beds, including those in the vicinity of sensitive-rich habitats such as hydrothermal vents, raise a mounting concern about the damage that such actions might originate to these poorly-know ecosystems, which represent millions of years of evolution and adaptations to extreme environmental conditions. It has been suggested that mining may cause a major impact on vent ecosystems and other deep-sea areas. Yet, the scale and the nature of such impacts are unknown at present. Hence, building upon currently available scientific information it is crucial to develop new cost-effective technologies embedded into rigorous operating frameworks. The forward-thinking provided here will assist in the development of new technologies and tools to address the major challenges associated with deep sea-mining; technologies for in situ and ex situ observation and data acquisition, biogeochemical processes, hazard assessment of deep-sea mining to marine organisms and development of modeling tools in support of risk assessment scenarios. These technological developments are vital to validate a responsible and sustainable exploitation of the deep-sea mineral resources, based on the precautionary principle.

Assays with Daphnia magna and Danio rerio as alert systems in aquatic toxicology.

For the evaluation and monitoring of the water quality, a series of methodologies, which have as basis an ample variety of bioindicators, may be applied. The aim of this research was to evaluate the use of ecotoxicity assays with Daphnia magna and Danio rerio as alert systems in water contaminated with toxic substances. Using two toxicity databases, the sensibility of those aquatic organisms to a wide variety of chemical products and elements and to some chemical categories was investigated. The relation between the reference dose for human oral chronic exposure (RfD) of all chemical products and the acute toxicity values for both bioindicators was also studied. Acute toxicity tests with D. magna respond to a larger variety of chemicals with a higher sensitivity than those with D. rerio. Although mammals, crustaceans and fish have different routes of exposure, target organs and toxic mechanisms, acute toxicity essays with fish and Daphnia may be used as an initial screening before mammal models are used.

Comparing LDA-1/2, HSE03, HSE06 and G0W0 approaches for band gap calculations of alloys.

It has long been known that the local density approximation and the generalized gradient approximation do not furnish reliable band gaps, and one needs to go beyond these approximations to reliably describe these properties. Among alternatives are the use of hybrid functionals (HSE03 and HSE06 being popular), the GW approximation or the recently proposed LDA-1/2 method. In this work, we compare rigorously the performance of these four methods in describing the band gaps of alloys, employing the generalized quasi-chemical approach to treat the disorder of the alloy and to obtain judiciously the band gap for the entire compositional range. Zincblende InGaAs and InGaN were chosen as prototypes due to their importance in optoelectronic applications. The comparison between these four approaches was guided both by the agreement between the predicted band gap and the experimental one, and by the demanded computational effort (time and memory). We observed that the HSE06 method provided the most accurate results (in comparison with experiments), whereas, surprisingly, the LDA-1/2 method gave the best compromise between accuracy and computational resources. Due to its low computational cost and good accuracy, we decided to double the supercell used to describe the alloys, and employing LDA-1/2 we observed that the bowing parameter changed remarkably, only agreeing with the measured one for the larger supercell, where LDA-1/2 plays an important role.

Sexual behaviour in the city of Lisbon.

This study of sexual behaviour in the city of Lisbon is based on data obtained from 2 random samples, one of individuals aged 16-20 (n = 400) and another of individuals over the age of 20 (n = 400). Samples have been stratified by district, gender and age. Data were obtained by personal interview and by questionnaires completed confidentially by the interviewees. The data include the age of first sexual intercourse, the number of sexual partners, the prevalence of casual relations and the type of sexual practices according to sex and age group. Results show that despite the high risk of exposure to HIV in a significant percentage of the population, AIDS is seen as a personal threat by only 20% of the population. Six per cent of the adults (aged 21 and over) and 12% of the young people (16-20) replied that they had not yet considered the problem; 73.5% of the adults and 67.4% of the young people stated that they did not feel threatened by the disease. Data suggest that the differences between men and women have decreased. Among the sexually active population, only 12% of individuals under 21 and 8% of the adults use condoms regularly. The awareness of infidelity among couples is much lower than in reality.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of HIV-2 infection in a family planning clinic in Lisbon.

A significant proportion (10%) of notified AIDS cases in Portugal are due to HIV-2 infection as a result of the close connections of Portugal with Western African Countries (ex-Portuguese colonies) where there is a high HIV-2 seroprevalence. We conducted a seroepidemiological study of HIV-1 and HIV-2 infection in 1400 women attending family planning and antenatal clinics in a health centre in Lisbon with the objective of analysing whether there was evidence of HIV-2 spread in this population. The seroprevalence for HIV, as determined by ELISA and confirmed by Western Blot, was 0.42% (6 cases) and 50% of these were of HIV-2 infection. Analysis of the epidemiological inquiries reveals that out of the 6 seropositive cases, only one was a drug addict (HIV-1) and another a western African black woman (HIV-2). The other 4 cases (2 HIV-2 and 2 HIV-1) were white Portuguese women with no history of travelling to Africa or previous blood transfusions, and the only risk factor was a history of multiple sexual partners (in 3 out of 4).

Sexually transmitted diseases and reproductive tract infections among contraceptive users.

OBJECTIVE: To establish the association between the use of contraceptives and the prevalence of sexually transmitted diseases (STD) and other reproductive tract infections (RTI). METHODS: 840 women who used contraception and who attended the Fundação Nossa Senhora do Bom Sucesso's Family Planning Clinic (FNSBS-FPC) over a 2-year period (1993-1994) were studied. All women answered a standard epidemiological survey and underwent a clinical laboratory assessment. The Chi-square test and a logistic regression model were used for statistical analysis. RESULTS: The majority of women were young (58.7%); low educational achievers (59.0%); middle or working class (85.0%); had a fixed partner (79.8%), and were of non-African origin (95.6%). Of the 627 women who responded, 4.1% stated that their sexual behavior was of high risk. The prevalence of any infection and particularly of bacterial vaginosis (BV), was highest among users of the intra-uterine device (IUD). Use of an IUD (P = 0.001) and high risk behavior (P = 0.04) were the variables associated to presence of a STD/RTI in multiple regression analysis. CONCLUSION: Results suggest that STD/RTIs basically occur due to high risk behavior and that, with the exception of an association between use of IUD and BV, the method of contraception does not affect the incidence of these infections.

[Contributions to the history of burn treatment]. / Contributos para a história do tratamento de queimados.

The authors make a brief review of burn treatment in Portugal as well as describing the Burn Unit of the Coimbra University Hospitals. The scientific advances in this area and new perspectives to the future are also mentioned, emphasizing the importance of burn prevention and a complete social reintegration of the burn patient.

[Avulsion of the skin of the penis and scrotum]. / Avulsão cutânea péno-escrotal.

The authors present a case report of traumatic avulsion of the skin of the penis and scrotum. Surgical treatment was performed in one surgical stage a few hours after the accident. The skin repair of the penis was carried out with a skin graft, while scrotum reconstruction was performed with fasciocutaneous flaps of the inner face of the thighs, with supero-medial pedicle, achieving a good result. The authors justify their choice of procedure, also mentioning the other methods most employed.

[Chlamydia trachomatis in family planning. Is screening necessary?]. / Infecção cervical a chlamydia trachomatis em planeamento familiar. E o rastreio necessário?

The authors used cellular cultures obtained from endocervix samples in order to determine the predominant factors of infection caused by Chlamydia trachomatis in a population of 391 women who attended a family planning consultation. The authors studied the relation between the infection and the following variables: age, geographical origin, social class, marital status, history of sexually transmitted diseases (STD), risk behaviours, contraceptive methods and attitudes towards both the disease and therapy. Chlamydia trachomatis was isolated in 7 women (1,8%). The highest infection rates were found in the following categories: women between the ages of 35-40 (4,9%), women who resort to hormonal contraception (3,4%), women between the ages of 20-25 (3,2%) and single women and/or women who do not have a regular partner (2,6%). No statistically relevant relation between the above variables and the infection was found, although a relatively high risk was revealed for women who resort to hormonal contraception (O.R = 7,4). The authors have concluded the following: 1. There is no need to proceed with the systematic universal screening of infection caused by Chlamydia trachomatis in the yearly family planning consultations for the low risk STD populations; 2. Hormonal contraception is a factor to be considered when selecting the women to be screened; 3. The yearly gynaecological supervision of women who attend family planning consultations is an important factor in checking the disease; 4. Information on the couple's attitude towards the disease and therapy is essential in the prevention of relapses.

[Prevalence of HIV1 and HIV2 infection in women living in an area of Lisboa City]. / Análise da seroprevalência da infecção pelo HIV1 e HIV2 em mulheres residentes numa área da cidade de Lisboa.

A seroprevalence study of HIV1 and HIV2 infection in women attending a Family Planning and an Antenatal Clinic was done in an area of the city of Lisbon where 7% of the population is of African origin. The protocol of study was of non linked type although with the possibility of collecting a second sample of blood for confirmation of results. Epidemiological, social and clinical data were collected from 1390 women and this was followed by the collection of a blood sample for the seroepidemiological study of HIV1 and HIV2. The population that was submitted to blood tests (75%) was compared to the one that missed the test and it was found that no important differences were present between the two. The criteria for HIV1 or HIV2 positive results were the presence of a positive ELISA test confirmed by an Western Blot revealing antibodies against the three proteins env, core and gag. For a test to be considered positive results by both methods had to be found in a second sample collected later. The prevalences of infection were of 0.29% for HIV1 and 0.29% for HIV2 although the prevalence of HIV2 in the population of African origin was higher (1.45%). The six seropositive cases detected included a drug addict, one prostitute, one case of African origin and two cases with multiple sexual partners. The clinical, epidemiological and immunological features of the seropositive cases are presented and the prevalence found is discussed in the context of other portuguese data.(ABSTRACT TRUNCATED AT 250 WORDS)