Cerebral microbleeds. Utility of SWI sequences.

OBJECTIVES: Define the concept of cerebral microbleeds (CMBs) and describe the most useful MRI sequences for detecting this finding. Review the entities that most frequently present with CMBs and that may benefit from the use of susceptibility-weighted imaging (SWI) sequences. CONCLUSIONS: SWI is a useful MRI sequence for the detection and characterization of microhemorrhages, venous structures and other sources of susceptibility in imaging. SWI is particularly sensitive to local magnetic field inhomogeneities generated by certain substances and is superior to T2* GRE sequences for this assessment. CMBs may be seen in different neurologic conditions, in certain infrequent clinical contexts and have a key role as a biomarker status in gliomas (ITTS) and as a marker of inflammatory activity in multiple sclerosis.

Analysis of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with monogenic PRKN and LRRK2 forms of Parkinson's disease.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most common surgical treatment for Parkinson's disease (PD). Patient selection and genetic background can modify the response to this treatment. The objective of this study was to compare both clinical and pharmacologic response of STN-DBS between patients with monogenic forms of PD and non-mutation carriers with idiopathic PD. METHODS: A retrospective analysis among 23 carriers of genetic mutations (8 PRKN and 15 LRRK2) and 74 patients with idiopathic PD was performed. The study included comparisons of Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, Schwab and England (S&E) scale values, Hoehn & Yahr (H&Y) stage scores, and equivalent doses of levodopa before and after the surgery (at 6 and 12 months) between both groups. RESULTS: The mean age at the time in which STN-DBS was performed was 59.5 ± 8.6. Linear mixed models showed the absence of statistically significant differences between mutation and non-mutation carriers regarding levodopa doses (p = 0.576), UPDRS II (p = 0.956) and III (p = 0.512) scores, and S&E scale scores (0.758). The only difference between the two groups was observed with respect to H&Y stage in OFF medication/ON stimulation status being lower in genetic PD at 6 months after surgery (p = 0.030). CONCLUSION: Clinical and pharmacological benefit of bilateral STN-DBS is similar in PRKN and LRRK2 mutation carriers and patients with idiopathic PD.

Rol de enfermería en el área COVID en un hospital pediátrico de alta complejidad / The role of nurses in the COVID area in a pediatric tertiary-care hospital

Introducción: la pandemia por SARS-CoV-2 planteó un desafío para todo el equipo de salud. Fue necesario analizar y pensar en este contexto el rol de enfermería en la atención y cuidados del paciente y su familia. Los procesos asistenciales debieron adaptarse a nuevas y diversas situaciones que generaron la atención de pacientes en su mayoría con comorbilidades asociadas. El objetivo del trabajo fue describir el rol de enfermería y la implementación de diversos protocolos y procesos de atención de pacientes en salas de internación pediátrica del área COVID de un hospital de alta complejidad. Material y métodos: se realizó un estudio retrospectivo y descriptivo sobre el personal de enfermería que participó en la atención de casos sospechosos o confirmados de COVID-19 durante la pandemia y los protocolos implementados para los cuidados de enfermería. Resultados: solo el 52.5% (n 79) del personal tenía experiencia mayor a tres años, el 75% (n: 113) pertenecían al género femenino, el 47% (n: 71) eran licenciados en enfermería. Conclusiones: Los profesionales enfermeros han logrado mediante sus fortalezas disciplinares dar respuesta a las necesidades del paciente pediátrico y su familia frente a la crisis sanitaria. Las competencias desarrolladas en la administración de los recursos disponibles, la adaptación, flexibilidad a los procesos y líneas estratégicas en tiempo real, posicionan al enfermero como un valor fundamental en el cuidado asistencial (AU)

Introduction: The SARS CoV-2 pandemic posed a challenge for the entire healthcare team. It was necessary to analyze and reflect on the role of nursing in the care of patients and their families in this context. Care processes had to be adapted to new and diverse situations that were generated by the care for patients who usually had associated comorbidities. The aim of the study was to describe the nursing role and the implementation of different protocols and processes for patient care in pediatric inpatient wards in the COVID area of a tertiary-care hospital. Material and methods: a retrospective descriptive study was conducted in the nursing personnel involved in the care of suspected or confirmed cases of COVID-19 during the pandemic and the protocols implemented for nursing care. Results: only 52.5% (n: 79) of the personnel had more than three years of experience, 75% (n: 113) were female, and 47% (n: 71) had a nursing degree. Conclusions: Through their disciplinary strengths, nursing professionals have been able to respond to the needs of pediatric patients and their families in the face of the health crisis. The skills developed in the management of available resources, adaptation, and flexibility to processes and real-time strategies, have positioned nurses as a fundamental factor in healthcare (AU)

Evaluation of point-of-care algorithms to detect diabetes during screening for latent TB infection.

BACKGROUND: Individuals with both diabetes mellitus (DM) and TB infection are at higher risk of progressing to TB disease.OBJECTIVE: To determine DM prevalence in populations at high risk for latent TB infection (LTBI) and to identify the most accurate point-of-care (POC) method for DM screening.METHODS: Adults aged ≥25 years were recruited at health department clinics in Hawaii and Arizona, USA, and screened for LTBI and DM. Screening methods for DM included self-report, random blood glucose (RBG), and POC hemoglobin A1c (HbA1c). Using HbA1c ≥6.5% or self-reported history as the gold standard for DM, we compared test strategies to determine the most accurate method while keeping test costs low.RESULTS: Of 472 participants, 13% had DM and half were unaware of their diagnosis. Limiting HbA1c testing to ages ≥30 years with a RBG level of 120-180 mg/dL helped identify most participants with DM (sensitivity 85%, specificity 99%) at an average test cost of US$2.56 per person compared to US$9.56 per person using HbA1c for all patients.CONCLUSION: Self-report was insufficient to determine DM status because many participants were previously undiagnosed. Using a combination of POC RBG and HbA1c provided an inexpensive option to assess DM status in persons at high risk for LTBI.

Rates of Screening for Breast, Colorectal, and Cervical Cancers in Older People With Cognitive Impairment or Dementia: A Meta-Analysis.

Purpose: Cancer screening may not be appropriate for some older people. We compare the likelihood of screening for colorectal, breast, and cervical cancers in older people with versus without cognitive impairment or dementia. Method: Systematic search of MEDLINE, Embase, and PsycINFO (to March 9, 2018) for articles reporting screening for colon, breast, and cervical cancers in patients with and without cognitive impairment or dementia. Studies were summarized quantitatively (random effects meta-analysis), according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Studies reported data 1989-2008. The rate of screening for breast cancer by mammography was lower in women with cognitive impairment or dementia compared with those without (pooled odds ratio [OR] = 0.81, 95% confidence interval [CI] = [0.71, 0.91], p = .0007, six studies, N = 18,562). The rates of screening for cervical cancer by Pap smear (pooled OR = 0.88, 95% CI = [0.71, 1.08], p = 0.22, five studies, N = 409,131) and colorectal cancer by fecal occult blood test (pooled OR = 0.87, 95% CI = [0.55, 1.38], p = .55, two studies, N = 2,718) were not significantly lower in people with cognitive impairment or dementia. Conclusion: These historical rates provide a baseline for discussions around the need for more specific guidance to assist with decisions to discontinue screening. The study also identifies a gap in reported knowledge with respect to screening under current guidelines.

Use of Comprehensive Geriatric Assessment and Geriatric Screening for Older Adults in the Radiation Oncology Setting: A Systematic Review.

AIMS: Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic process that evaluates medical, psychological, social and functional capacity. No systematic review of the use of CGA in radiation oncology has been conducted. This paper reviews the use of CGA in radiation oncology, examines whether such assessments are feasible and evaluates the effectiveness of these assessments in predicting and modifying outcomes. MATERIALS AND METHODS: We searched Medline, EMBASE, PsycINFO, CINAHL and the Cochrane Library for articles published between 1 January 1996 and 24 January 2017. RESULTS: Twelve non-randomised studies were identified; four studies used a geriatric screening tool only and the eight other studies combined a screening tool with a CGA. Most studies had small samples (mean 63 participants). Two studies identified a significant (95% confidence interval 1.5-4.8 and 1.5-6.9) association between an abnormal screening and increased risk of mortality. One study showed an ability of the CGA to influence treatment decision making, whereas six papers suggested a non-significant association between the screening tool/CGA and treatment tolerance. CONCLUSION: The studies suggest the feasibility of using a screening tool to select patients for CGA. 'Vulnerability' showed a non-statistically significant association with treatment tolerance, but a significant association with mortality.

Foliar phenolic compounds of ten wild species of Verbenacea as antioxidants and specific chemomarkers / Compostos fenólicos das folhas de dez especies selvagem de Verbenaceae como antioxidantes e quimiomarcadores específicos

Abstract The family Verbenaceae hosts important species used in traditional medicine of many countries. The taxonomic controversies concerning the specific delimitation of several of its species make it difficult to guarantee the botanical origin of herbal preparations based on species of this family. To contribute to the development of both specific chemomarkers and a quality control tool to authenticate the botanical origin of herbal preparations of Verbenacea species, we determined the foliar HPLC-DAD phenolic profiles and the antioxidant properties of 10 wild species of this family occurring in Mexico. The contents of phenols and flavonoids varied significantly among species. Priva mexicana showed the highest levels of total phenolics (53.4 mg g-1 dry tissue) and Verbena carolina had the highest levels of flavonoids (17.89 mg g-1 dry tissue). Relevant antioxidant properties revealed by antiradical and reducing power were found for the analyzed species. These properties varied significantly in a species-dependent manner. The phenolic compounds accumulated were flavones and phenolic acids. Flavones were the only type of flavonoids found. The results of a cluster analysis showed that the compounds were accumulated in species-specific profiles. The phenolic profiles are proposed as valuable chemomarkers that can become a useful tool for the quality control concerning the botanical origin of herbal medicinal preparations based on the species analyzed. In addition, phenolic profiles could contribute importantly to solve the taxonomic controversies concerning species delimitation in the family Verbenaceae.

Resumo A família Verbenaceae compreende importantes espécies utilizadas na medicina popular de muitos países. As dificuldades taxonômicas relativas à delimitação específica de muitas das suas espécies face difícil a verificar a origem botânico das preparações herbales baseadas nas espécies desta família. Para fazer uma contribuição ao desenvolvimento de indicadores taxonômicos e dum método de controle de qualidade para verificar a origem botânico de preparações herbales das espécies de Verbenaceae, os perfis fenólicos, obtidos pares HPLC-DAD, e as atividades antioxidantes das folhas de 10 espécies selvagens Mexicanas desta família foram determinados. Os conteúdos dos compostos fenólicos totais e dos flavonoides foram significativamente diferentes entre as espécies. Priva mexicana apresentou a maior quantidade de compostos fenólicos totais (53.4 mg g-1 amostra seca) e Verbena carolina apresentou a maior quantidade de flavonoides (17.89 mg g-1 amostra seca). Verifica-se importantes propriedades antioxidantes, como os resultados dos ensaios da capacidade antiradical e do poder redutor indicaram. As propriedades antioxidantes foram significativamente diferentes entre as espécies. Verificou-se que os compostos fenólicos conteúdos nas folhas das espécies analisadas foram só flavonas e ácidos fenólicos. Os resultados das análises de agrupamento provarãn que os perfiles fenólicos foram espécie-específicos. Estes perfis podem ser considerados como indicadores químicos da qualidade relativa à origem botânico de preparações medicinais baseadas nas espécies analisadas e podem fazer importantes contribuições para a delimitação específica na família Verbenaceae.

Role of 5α-dihydrotestosterone in testicular development of gilthead seabream following finasteride administration.

In teleosts, spermatogenesis is regulated by pituitary gonadotropins and sex steroids. 5α-dihydrotestosterone (DHT), derived from testosterone (T) through the action of 5α-reductase, has recently been suggested to play a physiologically important role in some fish species. In this study, gilthead seabream, Sparus aurata L., males received an implant of 1µgT/g body mass (bm) or vehicle alone and, 7days later, 1mg finasteride (FIN, an inhibitor of 5α-reductase)/kg bm or vehicle. Serum levels of T, 11-ketotestosterone (11KT), DHT and 17ß-estradiol (E2), and the mRNA levels of the main enzymes involved in their synthesis, were analysed. T promoted a transient increase in the serum levels of T, 11KT and E2 but a decrease in those of DHT at day 15 following T injection, in accordance with the up-regulation of mRNA levels of the enzymes involved in T transformation to 11KT (coding genes: cyp11b1 and hsd11b) and the down-regulation of mRNA levels of the enzyme responsible for T transformation to DHT (coding gene: srd5a). Interestingly, a similar effect was observed when FIN was injected. However, when fish were injected with T and FIN successively (T+FIN), control levels were not recovered at the end of the experimental period (28days). DHT seems to regulate E2 serum levels via the down-regulation of mRNA levels of aromatase (coding gene: cyp19a1a), which is needed for the transformation of T into E2. The testis histology, together with the proliferative rates recorded upon T, FIN or T+FIN treatment, suggests that DHT is involved in the onset of the meiotic phase of spermatogenesis.

17α-Ethynylestradiol alters the peritoneal immune response of gilthead seabream.

17α-Ethynylestradiol (EE2), a synthetic estrogen used in most oral contraceptives pills and hormone replacement therapies, is found in many water bodies, where it can modulate the fish immune response. EE2 acts as an endocrine disruptor in gilthead seabream, Sparus aurata L., a marine teleost fish of great economic value in Mediterranean aquaculture, as it induces hepatic vitellogenin gene (vtg) expression. Moreover, EE2 also alters the capacity of gilthead seabream to appropriately respond to infection although it does not behave as an immunosuppressor. Nevertheless, these previous studies have mainly focused on the head kidney leukocytes and no information exists on peritoneal leukocytes, including mast cells. In the present work, juvenile gilthead seabream fish were fed a pellet diet supplemented with EE2 for 76 days and intraperitoneally injected with hemocyanin plus imject alum adjuvant at the end of EE2 treatment and 92 days later, and the peritoneal immune response was analyzed. EE2 supplementation induced vtg expression but returned to basal levels by 3 months post-treatment. Interestingly, gilthead seabream peritoneal leukocytes express the genes encoding for the nuclear estrogen receptor α and the G protein-coupled estrogen receptor 1 and the dietary intake of EE2 induced these expression. Moreover, EE2 induced an inflammatory response in the peritoneal cavity in unvaccinated fish, which was largely maintained for several months after the cessation of the treatment. However, the impact of EE2 in vaccinated fish was rather minor and transient. Taken together, the study provides fresh information about endocrine immune disruption, focusing on peritoneal leukocytes.

Spectroscopic (far or terahertz, mid-infrared and Raman) investigation, thermal analysis and biological activity of piplartine.

Research in the field of medicinal plants including Piper species like long pepper (Piper longum L.- Piperaceae) is increasing all over the world due to its use in traditional and Ayurvedic medicine. Piplartine (piperlongumine, 5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)-pyridinone), a biologically active alkaloid/amide was isolated from the phytochemical investigations of Piper species, as long pepper. This alkaloid has cytotoxic, anti-fungal, anti-diabetic, anti-platelet aggregation, anti-tumoral, anxiolytic, anti-depressant, anti-leishmanial, and genotoxic activities, but, its anticancer property is the most promising and has been widely explored. The main purpose of the work is to present a solid state characterization of PPTN using thermal analysis and vibrational spectroscopy. Quantum mechanical calculations based on the density functional theory was also applied to investigate the molecular conformation and vibrational spectrum, which was compared with experimental results obtained by Raman scattering, far (terahertz) and mid-infrared adsorption spectroscopy. NBO analysis has been performed which predict that most intensive interactions in PPTN are the hyperconjugative interactions between n(1) N6 and π*(O1C7) having delocalization energy of 50.53kcal/mol, Topological parameters have been analyzed using 'AIM' analysis which governs the three bond critical points (BCPs), one di-hydrogen, and four ring critical points (RCPs). MEP surface has been plotted which forecast that the most negative region is associated with the electronegative oxygen atoms (sites for nucleophilic activity). Theoretically, to confirm that the title compound has anti-cancer, anti-diabetic and anti-platelet aggregation activities, it was analyzed by molecular docking interactions with the corresponding target receptors. The obtained values of H-bonding parameters and binding affinity prove that its anti-cancer activity is the more prominent than the other properties.

Foliar phenolic compounds of ten wild species of Verbenacea as antioxidants and specific chemomarkers

Abstract The family Verbenaceae hosts important species used in traditional medicine of many countries. The taxonomic controversies concerning the specific delimitation of several of its species make it difficult to guarantee the botanical origin of herbal preparations based on species of this family. To contribute to the development of both specific chemomarkers and a quality control tool to authenticate the botanical origin of herbal preparations of Verbenacea species, we determined the foliar HPLC-DAD phenolic profiles and the antioxidant properties of 10 wild species of this family occurring in Mexico. The contents of phenols and flavonoids varied significantly among species. Priva mexicana showed the highest levels of total phenolics (53.4 mg g-1 dry tissue) and Verbena carolina had the highest levels of flavonoids (17.89 mg g-1 dry tissue). Relevant antioxidant properties revealed by antiradical and reducing power were found for the analyzed species. These properties varied significantly in a species-dependent manner. The phenolic compounds accumulated were flavones and phenolic acids. Flavones were the only type of flavonoids found. The results of a cluster analysis showed that the compounds were accumulated in species-specific profiles. The phenolic profiles are proposed as valuable chemomarkers that can become a useful tool for the quality control concerning the botanical origin of herbal medicinal preparations based on the species analyzed. In addition, phenolic profiles could contribute importantly to solve the taxonomic controversies concerning species delimitation in the family Verbenaceae.

Resumo A família Verbenaceae compreende importantes espécies utilizadas na medicina popular de muitos países. As dificuldades taxonômicas relativas à delimitação específica de muitas das suas espécies face difícil a verificar a origem botânico das preparações herbales baseadas nas espécies desta família. Para fazer uma contribuição ao desenvolvimento de indicadores taxonômicos e dum método de controle de qualidade para verificar a origem botânico de preparações herbales das espécies de Verbenaceae, os perfis fenólicos, obtidos pares HPLC-DAD, e as atividades antioxidantes das folhas de 10 espécies selvagens Mexicanas desta família foram determinados. Os conteúdos dos compostos fenólicos totais e dos flavonoides foram significativamente diferentes entre as espécies. Priva mexicana apresentou a maior quantidade de compostos fenólicos totais (53.4 mg g-1 amostra seca) e Verbena carolina apresentou a maior quantidade de flavonoides (17.89 mg g-1 amostra seca). Verifica-se importantes propriedades antioxidantes, como os resultados dos ensaios da capacidade antiradical e do poder redutor indicaram. As propriedades antioxidantes foram significativamente diferentes entre as espécies. Verificou-se que os compostos fenólicos conteúdos nas folhas das espécies analisadas foram só flavonas e ácidos fenólicos. Os resultados das análises de agrupamento provarãn que os perfiles fenólicos foram espécie-específicos. Estes perfis podem ser considerados como indicadores químicos da qualidade relativa à origem botânico de preparações medicinais baseadas nas espécies analisadas e podem fazer importantes contribuições para a delimitação específica na família Verbenaceae.

Modelo de atención del cáncer en la infancia y adolescencia / Model of cancer care for children and adolescents

La atención integral de niños y adolescentes con cáncer es uno de los grandes desafíos para el sistema de salud pública de nuestros países donde el cáncer infantil representa un problema de salud pública y un problema social. El cáncer pediátrico en Paraguay, un país de escasos recursos, es un problema social y de salud pública por las consecuencias que se infringen a los pacientes, sus familias, las comunidades y los sistemas de salud. Un modelo descentralizado con clínicas más cercanas y dedicadas a cuidados primarios y referencias de niños con diagnóstico potencial de cáncer mejoraron el acceso a cuidados especializados y seguimiento del cáncer. Estas clínicas, implementadas dentro de los hospitales regionales de los sistemas nacionales de salud, ofrecen soluciones sostenibles y efectivas para un mejor acceso y seguimiento del cuidado de los niños con cáncer. El análisis de los desafíos, el éxito y la rentabilidad de estas clínicas regionales de cáncer pediátrico para referencias y seguimiento, permite sugerir un modelo óptimo para tales clínicas en entornos de bajos ingresos. Este modelo podría ser replicado para el cuidado de otras enfermedades y en otros grupos de edad. Presentamos aquí el resultado de la evaluación de los resultados de los pacientes de las cuatro clínicas regionales desde su implementación inicial.

Comprehensive care for children and adolescents with cancer is one of the major challenges for the public health system in our countries where childhood cancer represents a public health problem and a social problem. Pediatric cancer in Paraguay, a country with limited resources, is a social and public health problem because of the consequences that are inflicted on patients, their families, communities and health systems. A decentralized care model with closer-to-home clinics dedicated to primary care and referrals of children with a potential cancer diagnosis improved access to specialized care and cancer follow-up. These clinics, implemented within the regional hospitals of national health systems, offer sustainable and effective solutions for better access and follow-up care for children with cancer. An analysis of the challenges, success and cost-effectiveness of these regional pediatric cancer clinics for referral and follow-up allows us to suggest an optimal model for such clinics in low-income settings. This model could be replicated for the care of other diseases and in other age groups. We present here the results of the evaluation of the results of the patients of the four regional clinics since its initial implementation.

Selective estrogen receptor modulators differentially alter the immune response of gilthead seabream juveniles.

17α-ethynylestradiol (EE2), a synthetic estrogen used in oral contraceptives and hormone replacement therapy, tamoxifen (Tmx), a selective estrogen-receptor modulator used in hormone replacement therapy, and G1, a G protein-coupled estrogen receptor (GPER) selective agonist, differentially increased the hepatic vitellogenin (vtg) gene expression and altered the immune response in adult gilthead seabream (Sparus aurata L.) males. However, no information exists on the effects of these compounds on the immune response of juveniles. This study aims, for the first time, to investigate the effects of the dietary intake of EE2, Tmx or G1 on the immune response of gilthead seabream juveniles and the capacity of the immune system of the specimens to recover its functionality after ceasing exposures (recovery period). The specimens were immunized with hemocyanin in the presence of aluminium adjuvant 1 (group A) or 120 (group B) days after the treatments ceased (dpt). The results indicate that EE2 and Tmx, but not G1, differentially promoted a transient alteration in hepatic vtg gene expression. Although all three compounds did not affect the production of reactive oxygen intermediates, they inhibited the induction of interleukin-1ß (il1b) gene expression after priming. Interestingly, although Tmx increased the percentage of IgM-positive cells in both head kidney and spleen during the recovery period, the antibody response of vaccinated fish varied depending on the compound used and when the immunization was administered. Taken together, our results suggest that these compounds differentially alter the capacity of fish to respond to infection during ontogeny and, more interestingly, that the adaptive immune response remained altered to an extent that depends on the compound.

Tamoxifen disrupts the reproductive process in gilthead seabream males and modulates the effects promoted by 17α-ethynylestradiol.

17α-Ethynylestradiol (EE2), which is used in oral contraceptives and hormone replacement therapy, is a well documented estrogenic endocrine disruptor and an aquatic contaminant. In the present study, adult male specimens of the marine hermaphrodite teleost gilthead (Sparus aurata L.) were fed a diet containing tamoxifen (Tmx), an estrogen receptor ligand used in cancer therapy, alone or combined with EE2, for 25 days and then fed a commercial diet for a further 25 days (recovery period). The effects of short (5days) and long (25 days) treatments on several reproductive and gonad immune parameters and the reversibility of the disruptive effects after the recovery period were examined. Our data showed that Tmx acted as an estrogenic endocrine disruptor as revealed by the increase in the hepatic transcription of the vitellogenin gene in males, the serum levels of 17ß-estradiol and the gonad expression levels of the estrogen receptor α and G protein-coupled estrogen receptor genes, and the recruitment of leukocytes into the gonad, a well known estrogenic-dependent process in gilthead seabream males. On the other hand, Tmx also increased sperm concentration and motility as well as the serum levels of androgens and the expression levels of genes that codify for androgenic enzymes, while decreasing the expression levels of the gene that code for gonadal aromatase. When applied simultaneously, Tmx and EE2 could act in synergy or counteract, each other, depending on the parameter measured. The disruptive effect of EE2 and/or Tmx was not reversible after a 25 day recovery period.

Tamoxifen persistently disrupts the humoral adaptive immune response of gilthead seabream (Sparus aurata L.).

There is increasing concern about the possible effect of pharmaceutical compounds may have on the fish immune system. Bath exposition of 17α-ethynylestradiol (EE2), a synthetic estrogen used in oral contraceptives, altered the immune response of the gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost. Tamoxifen (Tmx) is a selective estrogen-receptor modulator used in hormone replacement therapy, the effects of which are unknown in fish immunity. This study aims to investigate the effects of dietary administration of EE2 (5 µg/g food) and Tmx (100 µg/g food) on the immune response of gilthead seabream, and the capacity of the immune system to recover its functionality after a recovery period. The results show for the first time the reversibility of the effect of EE2 and Tmx on the fish immune response. Tmx promoted a transient alteration in hepatic vitellogenin gene expression of a different magnitude to that produced by EE2. Both, EE2 and Tmx inhibited the induction of interleukin-1ß gene expression while reversed the inhibition of ROI production in leukocytes following vaccination. However, none of these effects were observed after ceasing EE2 and Tmx exposure. EE2 and Tmx stimulated the antibody response of vaccinated fish although Tmx, but not EE2, altered the antibody response and modulated the percentage of IgM(+) B lymphocytes of vaccinated fish during the recovery phase. Taken together, our results suggest that EE2 and Tmx might alter the capacity of fish to appropriately respond to infection and show that Tmx has a long-lasting effect on humoral adaptive immunity.

Specific and non-overlapping functions of testosterone and 11-ketotestosterone in the regulation of professional phagocyte responses in the teleost fish gilthead seabream.

Sex hormones, both estrogens and androgens, have a strong impact on immunity in mammals. In fish, the role of androgens in immunity has received little attention and contradictory conclusions have been obtained. However, it is well known that sex steroids are involved in fish growth, osmoregulation and gonad remodelation. In this study, we examine the in vitro effects of testosterone and 11-ketotestosterone, the two main fish androgens, on the professional phagocytes of the teleost fish gilthead seabream (Sparus aurata L.). Although both testosterone and 11-ketotestosterone failed to modulate the respiratory burst of seabream phagocytes, testosterone but not 11-ketotestosterone was able to increase the phagocytic ability of non-activated phagocytes. Curiously, 11-ketotestosterone was more powerful than testosterone at inducing the expression of its own receptor, namely androgen receptor b (ARb), in acidophilic granulocytes (AGs), but none of them affected the basal ARb expression levels in macrophages (MØ). Furthermore, although physiological concentrations of testosterone exerted a pro-inflammatory effect on both AGs and MØs, 11-ketotestosterone showed an anti-inflammatory effect in AGs and a strong pro-inflammatory effect in MØs. Interestingly, both androgens modulated the expression of toll-like receptors in these two immune cell types, suggesting that androgens might regulate the sensitivity of phagocytes to pathogens and damage signals. Testosterone and 11-ketotestosterone have a competitive effect, at least, on the modulation of the expression of some genes. Therefore, our results show for the first time a non-overlapping role for testosterone and 11-ketotestosterone in the regulation of professional phagocyte functions in fish.

[Assisted techniques for the endovascular treatment of complex or atypical cerebral aneurysms]. / Técnicas asistidas para el tratamiento endovascular de aneurismas cerebrales complejos o atípicos.

In the last ten years, the endovascular approach to the management of cerebral aneurysms has gone from being an alternative to surgery to being the first-choice technique in the vast majority of cases. The continuous development of new assisted techniques and of new materials for embolization have multiplied its therapeutic possibilities, so that safe and efficacious endovascular treatment is now possible for aneurysms that would have required surgery only a few years ago. These continuous technological advances require the professionals that treat patients with cerebral aneurysms to achieve a high degree of specialization and to keep up to date through continuous training. In this article, we review some of the most widely used assisted techniques in the endovascular treatment of cerebral aneurysms, discussing their main indications, their advantages over conventional embolization techniques, and their possible limitations.

In situ forming microparticle implants for delivery of sex steroids in fish: Modulation of the immune response of gilthead seabream by testosterone.

Current knowledge on the sensitivity of marine fish to androgenic environmental chemicals is limited, despite the growing interest in the effects of endocrine disrupting chemicals. To study in vivo the effects of testosterone (T) on the fish immune response, we used a microencapsulation implant technique, the in situ forming microparticle system, containing 1 mg T/kg body weight (T-ISM), in adult specimens of gilthead seabream (Sparus aurata L.), a species of great economic interest. We demonstrated that implants themselves (without T) have no significant effect on most of the parameters measured. In T-ISM implanted fish, T serum levels reached supraphysiological concentrations accompanied by a slight increase in 11-ketotestosterone and 17ß-estradiol levels 21 days post-implantation (dpi). Liver and head-kidney samples were processed 7 and 21 dpi to assess T-ISM effect on (i) the mRNA expression of genes involved in the metabolism of steroid hormones and in the immune response, and (ii) phagocyte activities. The expression profile of cytokines, chemokines and immune receptors was altered in T-ISM implanted animals that showed an early pro-inflammatory tendency, and then, a mixed pro-/anti-inflammatory activation during longer exposure. Furthermore, the enhancement of phagocytic activity and the production of reactive oxygen species by leukocytes 21 dpi in T-ISM implanted specimens suggest fine modulation of the innate immune response by T. Taken together, these data demonstrate for the first time the feasibility of using ISM implants in an aquatic species, and provide new data on the role played by T on the immune response in fish.

Study of polymorphism in imatinib mesylate: a quantum chemical approach using electronic and vibrational spectra.

Imatinib mesylate, 4-(4-methyl-piperazin-1-ylmethyl)-N-u[4-methyl-3-(4-pyridin-3-yl)pyrimidine-2-ylamino)phenyl]benzamide methanesulfonate is a therapeutic drug that is approved for the treatment of chronic myelogeneous leukemia (CML) and gastrointestinal stromal tumors (GIST). It is known that imatinib mesylate exists in two polymorphic forms α and ß. However, ß-form is more stable than the α-form. In this work, we present a detailed vibrational spectroscopic investigation of ß-form by using FT-IR and FT-Raman spectra. These data are supported by quantum mechanical calculations using DFT employing 6-311G(d,p) basis set, which allow us to characterize completely the vibrational spectra of this compound. The FT-IR spectrum of α-form has also been discussed. The importance of hydrogen-bond formation in the molecular packing arrangements of both forms has been examined with the vibrational shifts observed due to polymorphic changes. The red shift of the NH stretching bands in the infrared spectrum from the computed wavenumber indicates the weakening of the NH bond. The UV-vis spectroscopic studies along with the HOMO-LUMO analysis of both polymorphs (α and ß) were performed and their chemical activity has been discussed. The TD-DFT method was used to calculate the electronic absorption spectra in the gas phase as well as in the solvent environment using IEF-PCM model and 6-31G basis set. Finally, the results obtained complements to the experimental findings.