Involvement of monoaminergic targets in the antidepressant- and anxiolytic-like effects of the synthetic alkamide riparin IV: Elucidation of further mechanisms through pharmacological, neurochemistry and computational approaches.

Despite recent advances, current antidepressants have considerable limitations: late onset of action and the high profile of refractoriness. Biomedical research with natural products has gained growing interest in the last years, and had provide useful candidates for new antidepressants. Riparins are a group of natural alkamides obtained from Aniba riparia, which had marked neuroactive effects, mainly as antidepressant and antinociceptive agents. We made modifications of the basic structure of riparins, originating a synthetic alkamide, also known as riparin IV (RipIV). RipIV demonstrated a superior analgesic effect than its congeners and a marked antidepressant-like effect. However, the basic mechanism for the central effects of RipIV remains unknown. Here, we aimed to investigate the participation of monoaminergic neurotransmission targets in the antidepressant-like effects of RipIV. To do this, we applied a combined approach of experimental (classical pharmacology and neurochemistry) and computer-aided techniques. Our results demonstrated that RipIV presented antidepressant- and anxiolytic-like effects without modifying locomotion and motor coordination of mice. Also, RipIV increased brain monoamines and their metabolite levels. At the higher dose (100 mg/kg), RipIV increased serotonin concentrations in all studied brain areas, while at the lower one (50 mg/kg), it increased mainly dopamine and noradrenaline levels. When tested with selective receptor antagonists, RipIV antidepressant effect showed dependence of the activation of multiple targets, including D1 and D2 dopamine receptors, 5-HT2A/2, 5-HT3 receptors and α2 adrenergic receptors. Molecular docking demonstrated favorable binding conformation and affinity of RipIV to monoamine oxidase B (MAO-B), serotonin transporter (SERT), α1 receptor, D2 receptor, dopamine transporter (DAT) and at some extent GABA-A receptor. RipIV also presented a computationally predicted favorable pharmacokinetic profile. Therefore, this study demonstrated the involvement of monoaminergic targets in the mechanism of RipIV antidepressant-like action, and provide evidence of it as a promising new antidepressant.

Tuning the crystalline electric field and magnetic anisotropy along the CeCuBi2-xSbx series.

We have performed X-ray powder diffraction, magnetization, electrical resistivity, heat capacity and inelastic neutron scattering (INS) to investigate the physical properties of the intermetallic series of compounds CeCuBi2-xSbx. These compounds crystallize in a tetragonal structure with space group P4∕nmm and present antiferromagnetic transition temperatures ranging from 3.6 K to 16 K. Remarkably, the magnetization easy axis changed along the series, which is closely related to the variations of the tetragonal crystalline electric field (CEF) parameters. This evolution was analyzed using a mean field model, which included an anisotropic nearest-neighbor interactions and the tetragonal CEF Hamiltonian. We obtained the CEF parameters by fitting the magnetic susceptibility data with the constraints given by the INS measurements. More broadly, we discuss how this CEF evolution can affect the Kondo physics and the search for a superconducting state in this family.

Iliac Seal Zone Dynamics and Clinical Consequences After Endovascular Aneurysm Repair.

OBJECTIVE: To evaluate the dynamics of the iliac attachment zone after EVAR, and the association with clinical events. METHODS: A tertiary institution's prospective EVAR database was searched to identify common iliac arteries at risk. Internally validated measurements were made, using centre lumen line reconstructions. Iliac dilatation and endograft limb retraction were the main endpoints. Associations between dilatation, retraction, oversizing, and distal seal length were investigated. Association with clinical events (sealing or occlusion) was also explored. RESULTS: Of 452 primary EVAR patients treated from 2004 to 2012, 341 were included (mean age 72 years, 12% female, 597 common iliac arteries). Median follow-up was 4.7 years. At 30 days, the mean iliac diameter increased from 14 mm to 15 mm (p < .001). Over follow-up, it increased to 18 mm (p < .001). Iliac dilatation ≥20% occurred in 295 cases (49.4%) and exceeded the implanted endograft diameter in 170 (28.7%). Limb retraction ≥5 mm was identified in 54 patients (9.1%) and was associated with iliac seal complications (p < 0.001). Iliac endograft extension diameter ≥24 mm (OR 3.3, 95% CI 1.7-6.4) and iliac artery dilatation beyond the endograft (OR 2.1, 95% CI 1.2-3.8) were independent risk factors. Overall, there were 34 (5.7%) iliac seal complications. Retraction of the iliac endograft (OR 1.17 per mm, 95% CI 1.10-1.24) and baseline AAA diameter (1.04 per mm, 95% CI 1.01-1.07) were independent risk factors for seal related complications. Greater initial post-operative iliac seal length was protective (OR 0.94 per mm, 95% CI 0.90-0.97). CONCLUSIONS: Iliac dilatation and endograft retraction are common findings during follow-up, potentially leading to adverse clinical events. Optimisation of the iliac seal zone providing a long distal seal length and added attention to patients with large aneurysms or receiving ≥24 mm diameter iliac extensions are recommended. Also, long-term surveillance including CTA is advised to reveal and correct loss of seal at the iliac attachments before adverse clinical events occur.

Mid-Term Results of EVAR in Severe Proximal Aneurysm Neck Angulation.

OBJECTIVE: To determine if mid-term outcome following endovascular aneurysm repair (EVAR) with the Endurant Stent Graft (Medtronic, Santa Rosa, CA, USA) is influenced by severe proximal neck angulation. METHODS: A retrospective case-control study was performed using data from a prospective multicenter database. All measurements were obtained using dedicated reconstruction software and center-lumen line reconstruction. Patients with neck length >15 mm, infrarenal angle ß > 75°, and/or suprarenal angle α > 60°, or neck length >10 mm with ß > 60°, and/or α > 45° were compared with a matched control group. Primary endpoint was primary clinical success. Secondary endpoints were freedom from rupture, type 1A endoleak, stent fractures, freedom from neck-related reinterventions, and aneurysm-related adverse events. Morphological neck variation over time was also assessed. RESULTS: Forty-five patients were included in the study group and were compared with a matched control group with 65 patients. Median follow-up time was 49.5 months (range 30.5-58.4). The 4-year primary clinical success estimates were 83% and 80% for the angulated and nonangulated groups (p = .42). Proximal neck angulation did not affect primary clinical success in a multivariate model (hazard ratio 1.56, 95% confidence interval 0.55-4.41).Groups did not differ significantly in regard to freedom from rupture (p =.79), freedom from type 1A endoleak (p = .79), freedom from neck-related adverse events (p = .68), and neck-related reinterventions (p = .68). Neck angle reduction was more pronounced in patients with severe proximal neck angulation (mean deltaα -15.6°, mean deltaß -30.6°) than in the control group (mean deltaα -0.39°, mean deltaß -5.9°) (p < .001). CONCLUSION: Mid-term outcomes following EVAR with the Endurant Stent Graft were not influenced by severe proximal neck angulation in our population. Despite the conformability of the device, moderate aortic neck remodeling was identified in the group of patients with angulated neck anatomy on the first computed tomography scan after implantation with no important further remodeling afterwards. No device integrity failures were encountered.

Perfil do conhecimento de cuidadores de pacientes pediátricos sobre medicamentos prescritos / Profile of the knowledge of pediatric patient caregivers about prescribed medicines

O raro contato entre os profissionais de saúde e o cuidador do paciente pediátrico, associado ao pouco tempo disponibilizado pelo profissional farmacêutico durante a dispensação, não são suficientes para a geração de informações significativas, podendo acarretar falhas no fluxo de informação e não adesão involuntária do paciente ao tratamento. O objetivo do trabalho foi coletar dados sobre o perfil do conhecimento dos cuidadores de pacientes pediátricos a respeito de medicamentos dispensados na Farmácia Ambulatorial do Hospital Infantil Albert Sabin (HIAS), com enfoque para os medicamentos do Componente Especializado da Assistência Farmacêutica nas especialidades de Neurologia e Pneumologia. Trata-se de um estudo prospectivo. A coleta de dados ocorreu entre novembro de 2007 e maio de 2008, utilizando-se um questionário semiestruturado. De acordo com os dados coletados, 87,7% (n=50) eram do gênero feminino; o grau de escolaridade, predominante, foi o ensino médio completo; a renda média familiar ficou compreendida entre um e dois salários mínimos, equivalente a 63,1% dos casos. As questões sobre informações sobre os medicamentos dispensados configuraram-se dessa forma: 12% desconhecem o nome do medicamento prescrito; 14% desconhecem a indicação do medicamento; 7% desconhecem como administrá-lo; 29,8% desconhecem o tempo de tratamento; 82,5% desconhecem o que é reação adversa a medicamento. Foram consideradas como respostas insatisfatórias aquelas que não foram condizentes com as informações contidas nas bulas e/ou receituários médicos dos medicamentos. A análise dos dados permitiu verificar que há, em relação à falta de informação dos entrevistados, dados significantes que podem comprometer a terapia, prejudicando a saúde do paciente.

The rare contacts between health professionals and adult caregivers of pediatric patients in a hospital outpatient pharmacy, together with the short time available during the dispensing, are insufficient to generate a meaningful flow of information, and can lead to an unintentional lack of patient compliance to the treatment. The objective of the study was to collect data on the profile of knowledge of pediatric patient caregivers, regarding medicines dispensed in the outpatient pharmacy at the Hospital Infantil Albert Sabin (a childrens hospital), focusing on those who obtain medicines from the Specialized Pharmaceutical Care component of the Public Health Service, in the specialties of Neurology and Pulmonology. This prospective study was based on data collected from November 2007 to May 2008, using a semi-structured questionnaire. According to the results, 87.7% of the caregivers (n = 50) were female; they were predominantly educated to high school level; the median family income was between one and two times the ?minimum wage? (inflation-adjusted official subsistence wage), 63.1% of incomes falling within this range(?). Questions of fact about the medication dispensed elicited the following profile of respondents? knowledge: 12% did not know the name of the drug, 14% the reason for taking the drug, 7% how to administer the medicine, 29.8% the treatment time and 82.5% did not know about adverse reactions to the medication. Answers considered unsatisfactory were those that were inconsistent with the information contained in the package inserts and / or medical prescriptions of the drugs. Data analysis showed that there was a significant lack of information among the respondents that could impair the adherence to drug therapy and affect patient health.

Magnetic excitations in the spin-1 anisotropic Heisenberg antiferromagnetic chain system NiCl(2)-4SC(NH(2))(2).

NiCl(2)-4SC(NH(2))(2) (DTN) is a quantum S=1 chain system with strong easy-pane anisotropy and a new candidate for the Bose-Einstein condensation of the spin degrees of freedom. ESR studies of magnetic excitations in DTN in fields up to 25 T are presented. Based on analysis of the single-magnon excitation mode in the high-field spin-polarized phase and previous experimental results [Phys. Rev. Lett. 96, 077204 (2006)10.1103/PhysRevLett.96.077204], a revised set of spin-Hamiltonian parameters is obtained. Our results yield D=8.9 K, J(c) = 2.2 K, and J(a,b) = 0.18 K for the anisotropy, intrachain, and interchain exchange interactions, respectively. These values are used to calculate the antiferromagnetic phase boundary, magnetization, and the frequency-field dependence of two-magnon bound-state excitations predicted by theory and observed in DTN for the first time. Excellent quantitative agreement with experimental data is obtained.

[Complications of arterial catheterization in children]. / Complicações da cateterização arterial em crianças.

UNLABELLED: The radial artery catheterization with the purpose of children's monitoring has been more and more used in Pediatric Intensive Care Units, and many times, is use is indispensable, like in cardiac surgery post-operative cases. However, there are only a few articles on the subject among us. PURPOSE: To analyse the complications of radial artery catheterization in the post-operative of cardiac surgery in children. METHODS: We studied the complications of this procedure in 120 children in cardiac surgery post-operative range from 1 month to 2 years. The children were catheterized by percutaneous technique (n = 67) and by cutdown technique (n = 53). The following complications were analysed in relation to the placement time of the catheter and the used technique: local infection, hemorrhagic complication, ischemia, catheter occlusion and accidental catheter displacement. RESULTS: Infection, ischemia and hemorrhage were more frequent and statistically significant in patients submitted to cutdown technique, while the catheter occlusion and accidental displacement were similar in both groups. The placement time of the catheter was an important variable in our study. All of the other infection cases occurred after 72 hours of the catheterization and the frequency of hemorrhage and ischemia was higher in the first 72 hours. CONCLUSION: The main complications of this proceeding are related to the technic utilized, time of utilization of the catheter and to the characteristics of the patients.

Complicações da cateterização arterial em crianças / Complications of arterial catheterization in children

A cateterização da artéria radial para fins de monitorização em crianças graves, vem sendo utilizado cada vez com maior freqüência em unidades de cuidados intensivos pediátricos e, muitas vezes, a sua presença é imprescindível, como nos casos de choque e pós-operatório de cirurgia cardíaca, entretanto há poucas publicações em nosso meio a respeito do assunto. OBJETIVO: Analisar as complicações da cateterização da artéria radial para fins de monitorização no pós-operatório de cirurgia cardíaca em crianças. MÉTODOS: Estudamos as complicações deste procedimento em 120 crianças em pós-operatório de cirurgia cardíaca, com idades entre um mês e dois anos. As crianças foram cateterizadas por punção percutânea (n = 67) e por dissecação (n = 63). Foram analisadas as seguintes complicações, em relação à técnica utilizada e ao tempo de permanência do cateter: infecção local, hemorragia, isquemia, obstrução do cateter e perda acidental do cateter. RESULTADOS: A presença de infecção, isquemia e hemorragia foram maiores e estatísticamente significantes nos pacientes submetidos à dissecção, enquanto que a obstrução e a perda acidental do cateter foram semelhantes em ambos os grupos. Todos os casos de infecção ocorreram após 72 horas da cateterização e a freqüência de hemorragia e isquemia foi maior nas primeiras 72 horas. CONCLUSÃO: As principais complicações deste procedimento estão relacionadas à técnica utilizada, ao tempo de permanência do cateter e às características do paciente.

[Ratio of proportions and the use of the delta method for confidence intervals in logistic regression]. / Razões de proporções e uso do método delta para intervalos de confiança em regressão logística.

OBJECTIVE: To present an application of logistic regression modelling to estimate ratios of proportions, such as prevalence ratio or relative risk, and the Delta Method to estimate confidence intervals. METHOD: The Delta Method was used because it is appropriate for the estimation of variance of non-linear functions of random variables. The method is based on Taylor's series expansion and provides a good approximation of variance estimates. A computer program, utilizing the matrix module of SAS, was developed to compute the variance estimates. A practical demonstration is presented with data from a cross-sectional study carried out on a sample of 611 women, to test the hypothesis that the lack of housework sharing is associated with high scores of psychological symptoms as measured by a validated questionnaire. RESULTS: Crude and adjusted prevalence ratio estimated by logistic regression were similar to those estimated by tabular analysis. Also, ranges of the confidence intervals of the prevalence ratio according to the Delta Method were nearly equal to those obtained by the Mantel-Haenszel approach. CONCLUSIONS: The results give support to the use of the Delta Method for the estimation of confidence intervals for ratios of proportions. The method should be seen as an alternative for situations in which the need to control a large number of potential confounders limits the use of stratified analysis.

Haloperidol blood levels and clinical outcome: a meta-analysis of studies relevant to testing the therapeutic window hypothesis.

Haloperidol, the most studied antipsychotic drug, is the only one about which reliable statements on the relationship between blood levels and clinical outcome can be made. A systematic overview was undertaken to determine whether there was an optimum blood concentration range for clinical efficacy. Eighteen published studies which provided individual patient data in tables or graphs were reviewed. Clinical benefits tended to decline when the haloperidol blood concentration was increased above 26 ng/ml. Our data support the existence of a therapeutic window between 4 and 26 ng/ml for haloperidol in the treatment of schizophrenic, schizoaffective and schizophreniform disorders.

Candidiase renal: fungus-balls. / Renal candidiasis: fungus-balls

Os autores relatam um caso de candidiase renal em paciente jovem que apresentou anuria por massa fungica "fungal balls" no sistema pielocaliciano em rim unico

Intoxicacao experimental pelo cloreto de mercurio: lipoperoxidacao hepatica e renal. / Experimental HgCl2 poisoning: renal and hepatic lipid peroxidation

Ratos Wistar machos, com 30 dias de idade, foram submetidos a intoxicacao experimental, com 100 ppm de HgCl2, por via oral.Os niveis de lipoperoxidacao hepatica e renal foram avaliados, medindo-se a quantidade total de malonildialdeido (MDA) produzido por homogenados desses orgaos. Nao se obteve nenhuma alteracao na quantidade de MDA produzida pelos homogenados. Cortes histologicos desses orgaos, nos animais tratados, nao mostraram alteracoes, quando comparados com os do grupo controle