Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Maximizing the Impact of Voluntary Medical Male Circumcision for HIV Prevention in Zambia by Targeting High-Risk Men: A Pre/Post Program Evaluation.

A well-documented barrier to voluntary medical male circumcision (VMMC) is financial loss due to the missed opportunity to work while undergoing and recovering from VMMC. We implemented a 2-phased outcome evaluation to explore how enhanced demand creation and financial compensation equivalent to 3 days of missed work influence uptake of VMMC among men at high risk of HIV exposure in Zambia. In Phase 1, we implemented human-centered design-informed interpersonal communication. In Phase 2, financial compensation of ZMW 200 (~ US$17) was added. The proportion of men undergoing circumcision was significantly higher in Phase 2 compared to Phase 1 (38% vs 3%). The cost of demand creation and compensation per client circumcised was $151.54 in Phase 1 and $34.93 in Phase 2. Financial compensation is a cost-effective strategy for increasing VMMC uptake among high-risk men in Zambia, and VMMC programs may consider similar interventions suited to their context.

Environmental and economical assessment for a sustainable Zn/air battery.

Metal/Air batteries are being developed and soon could become competitive with other battery technologies already in the market, such as Li-ion battery. The main problem to be addressed is the cyclability, although some progress has been recently achieved. A Life Cycle Assessment (LCA) of the manufacturing process of a Zn/Air battery is presented in this article, including raw extraction and process of materials and battery assembly at laboratory scale (cradle to gate approach). The results indicate that Zn/Air battery can be fabricated with low environmental impacts in most categories and only four deserve attention (still being low impacts), such as Human Toxicity (cancer and non-cancer), Freshwater Ecotoxicity and Resource Depletion (the later one depending mainly on Zn use, which is not a critical material, but has a strong impact on this category). Cathode fabrication arises as the subassembly with higher impacts, followed by membrane, then anode and finally electrolyte. An economic cost calculation indicates that if cyclability of Zn/Air batteries is achieved, they can become competitive with other technologies already in the market.

Proximal composition and fatty acid profile of Hemigrapsus crenulatus (H. Milne Edwards, 1837) as one of the main foods of "patagonian blenny"Eleginops maclovinus (Cuvier, 1830).

The Patagonian blenny (Eleginops maclovinus) is species endemic to South America with physiological characteristics that would facilitate its incorporation into Chilean aquaculture. However, there is currently no specific artificial food that can be used to raise E. maclovinus. In light of this problem, this study describes the proximal composition and fatty acid profile of the crab Hemigrapsus crenulatus, one of the main foods of E. maclovinus. The purpose of the study is to serve as basic information for the development of a specific artificial diet for juveniles of this fish species. The proximal analysis of the complete body of H. crenulatus indicates that it is mainly composed of ash (35.9%), proteins (32.2%), glucides (19.8%) and minor lipids (3.6%). The fatty acid profile is 40.7% PUFAs, 29.7% MUFAs and 29.5% SAFAs, and the most abundant acids are Eicosapentaenoic (18.8%), Oleic (6.8%) and Palmitic (16.6%), respectively. H. crenulatus has highest level of proteins, lipids and PUFAs among the species of the Brachyura infraorder.

Fluorescence enhanced BA-LIFT for single cell detection and isolation.

Laser bioprinting is a term that refers to a group of laser-based techniques for printing living cells with high precision and good viability. Most of these techniques are based on modifications of the standard laser induced forward transfer technique (LIFT). When it comes to printing living material, direct laser irradiation should be avoided, therefore an indirect LIFT technique comprising an energy absorption layer should be used. This work presents a blister actuated-LIFT (BA-LIFT) technique which uses a commercial polyimide tape as a uniform energy absorption layer. To increase the potential of the technique for cell selection and printing accuracy, we take advantage of the high optical transmission of the polyimide layer to implement an in-line fluorescence and conventional imaging vision system coaxial with the laser path. With this system and using the appropriate staining methodology it is possible to track and identify different cell types, selecting those to be transferred and tracking cell survival both in the donor and acceptor substrates. We studied the BA-LIFT printability map for sodium alginate and methylcellulose hydrogels in the fluence range from 6.1 to 2.0 J cm-2 together with the cell viability assessment measured by our fluorescence system. The study has revealed that less concentrated, therefore less viscose hydrogel shows better results with lower fluences, whereas hydrogels with higher concentrations present better results at higher fluences. Also, at low fluences 98 % of cell viability was obtained, besides both primary cells and cell lines keep their integrity, proliferating and functional activity. The technique was tested by tracking and targeting mouse hematopoietic progenitor stem cells transferred to assess colony forming units; moreover, natural killer cells were isolated and its activation in a stimulation media was tracked with the fluorescence system.

Immunohistochemical distribution of AMPA-type label in the pigeon (C. livia) hippocampus.

The avian hippocampal formation (HF) is reported to have a role equivalent to that of the mammalian hippocampus, which may involve the glutamatergic system as well. In the present paper we offer evidence of the occurrence and distribution of the subunits composing AMPA-type glutamate receptors on neurons in the hippocampus region of the pigeon brain. The experiment analyzed the immunolabeling of glutamate receptor (GluR)(1)(,) GluR(4,) and GluR(2/3) receptor subunits in adult pigeons and found consistent evidence that neurons located in the five main areas of the avian HF have these AMPA-type subunits, but their incidence varies according to position and neuro-type. About 20%-35% of the irregular and 35%-70% of the triangular neurons on the lateral and medial "V" arms contain GluR(1) and GluR(2/3), while GluR(4) was found only at rounded neurons. The majority of the triangular neurons (over 90%) and about half of the irregular neurons in the medial area contain GluR(1) and GluR(2/3,) whereas the rounded neurons contain primarily GluR(4) (95%). Labeling revealed GluR(1) (40%-60%) and GluR(2/3) (30%) in the dorsomedial and lateral areas but only in irregular neurons, while 60%-80% of the rounded neurons synthesize GluR(4). While triangular and irregular neurons appear to match the description of projecting neurons, rounded ones seem to participate in local circuits. A discussion of the functional significance of the avian HF concentrates on a postulation of the "V" arms as equivalent to the dentate gyrus and the dorsomedial area being similar to the Ammon's horn.

Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment.

Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients. Graphical Abstract Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.

Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

Adaptation of a DBT Intervention to Reduce Self-harm in Borderline Personality Disorder

Borderline Personality Disorder (BPD) is characterized by instability that often leads to Non-Suicidal Self-Injury (NSSI) and greater healthcare utilization. Dialectical Behavioral Therapy (DBT) is useful although its long duration and the need for specialized therapists make it difficult to implement in low-resources settings, so brief interventions can complement DBT. The objective of the present study was to undertake cultural adaptation of a Brief, Manualized Intervention to reduce NSSI in the Mexican population with BPD. An experimental design with a single-case pilot study with replicas was used with seven women with a BPD diagnosis. Five to six online sessions were implemented and emotional dysregulation, experiential avoidance and NSSI were measured weekly. NAP index was calculated to assess the effect of the intervention. Most participants showed a large effect size in reducing NSSI and a moderate effect size in reducing emotional dysregulation. Moderate and small effect sizes were obtained in experiential avoidance. The intervention adapted and validated seems to be useful and serve as an additional therapeutically tool to complement usual treatment of patients with BPD (AU)

Avaliação dos parâmetros de qualidade físico-químicos de creme-géis à base de ácido hialurônico adquiridos em farmácias magistrais do município de Campo Grande-MS / Evaluation of the physicochemical quality parameters of cream-gels based on hyaluronic acid purchased in compounding pharmacies in the city of Campo Grande-MS / Evaluación de parámetros de calidad fisicoquímica de geles-crema a base de ácido hialurónico adquiridos en farmacias magistrales de la ciudad de Campo Grande-MS

RESUMO Introdução: ao longo dos anos, a busca pela melhora do autocuidado estendeu-se às farmácias com manipulação, onde o cosmético pode ser manipulado de acordo com as preferências de cada indivíduo. Dessa forma, é necessário prover a estabilidade para cada produto manipulado, garantindo que um cosmético seguro e eficaz será dispensado. O ácido hialurônico é um ativo que tem se tornado popular devido à sua capacidade de realizar a manutenção da elasticidade da pele e exercer função hidratante, além de atuar na redução de linhas de expressão. Objetivo: analisar a qualidade de dermocosméticos manipulados a base de ácido hialurônico de diferentes farmácias com manipulação no município de Campo Grande-MS, através de análises laboratoriais físico-químicas e de rotulagem. Material e métodos: quatro amostras de creme-gel à base de ácido hialurônico 5% foram adquiridas em farmácias magistrais, e realizadas as seguintes análises de controle de qualidade: análise organoléptica, determinação de pH, densidade, teste de centrífuga, espalhabilidade e análise de rotulagem. Resultados: em relação às análises, os resultados obtidos foram satisfatórios. A análise organoléptica, o teste de centrifugação e de espalhabilidade se encontraram dentro dos padrões estipulados; porém, destaca-se o ensaio de densidade, em que duas amostras obtiveram valores abaixo do estipulado; e para a análise de rótulos, nenhum produto continha lista de componentes da formulação. Conclusão: ao final das análises, pode ser apontado que os produtos apresentaram desempenho satisfatório em grande parte dos testes propostos e são uma opção segura, de boa qualidade e custo acessível ao público.

SUMMARY Introduction: Over the years, the search for improving self-care has extended to compound pharmacy, where the cosmetic can be manipulated according to the preferences of each person. Thus, it is necessary to provide stability for each product handled, ensuring that a safe and effective cosmetic will be dispensed. Hyaluronic acid is an active that has become popular due to its ability to maintain skin elasticity and exert a moisturizing function, in addition to acting in the reduction of fine lines. Aim: To analyze the quality of cosmetics manipulated with the active ingredient of Hyaluronic Acid from different compound pharmacies in the city of Campo Grande-MS, through physical-chemical laboratory analysis and labeling. Material and methods: Four samples of 5% hyaluronic acid-based cream-gel were acquired from master pharmacies, and the following quality control analyzes were carried out: organoleptic analysis, pH determination, density, centrifuge test, spreadability and labeling analysis. Results: Regarding the analyses, the results obtained were satisfactory. The organoleptic analysis, the centrifugation test and the spreadability were within the stipulated standards; however, the density test stands out, in which two samples obtained results below the stipulated; and for label analysis, no product contained a list of formulation components. Conclusion: At the end of the analyses, it can be pointed out that the products presented satisfactory performance in most of the proposed tests and are a safe option, of good quality and accessible to the public.

RESUMEN Introducción: a lo largo de los años, la búsqueda por mejorar el autocuidado se ha extendido a las farmacias, donde los cosméticos pueden ser manipulados según las preferencias de cada individuo. Por lo tanto, es necesario proporcionar estabilidad a cada producto manipulado, asegurando que se dispensará un cosmético seguro y eficaz. El ácido hialurónico es un activo que se ha popularizado por su capacidad para mantener la elasticidad de la piel e hidratarla, además de actuar para reducir las líneas de expresión. Objetivo: analizar la calidad de los dermocosméticos manipulados a base de ácido hialurónico de diferentes farmacias en Campo Grande-MS, mediante análisis de laboratorio físico-químico y marcaje. Material y métodos: se adquirieron en farmacias magistrales cuatro muestras de crema-gel a base de ácido hialurónico al 5%, y se realizaron los siguientes análisis de control de calidad: análisis organoléptico, determinación de pH, densidad, prueba de centrifugación, untabilidad y análisis de marcaje. Resultados: en cuanto a los análisis, los resultados obtenidos fueron satisfactorios. Las pruebas de análisis organoléptico, centrifugado y untabilidad estuvieron dentro de los estándares estipulados, sin embargo, se destaca la prueba de densidad, en la que dos muestras obtuvieron valores por debajo del valor estipulado y para el análisis de etiquetas, ningún producto contenía una lista de componentes de la formulación. Conclusión: los productos se desempeñaron satisfactoriamente en la mayoría de las pruebas propuestas y son una opción segura, con buena calidad y su costo accesible al público.

Monoaminergic markers in the optic tectum of the domestic chick.

The avian optic tectum has become a reliable model system to study the basic mechanisms that underlie the computation of visual stimuli. Many aspects of its cytoarchitecture, chemoarchitecture, connectivity and development are thoroughly characterized. However, knowledge about its monoaminergic innervation is still incomplete. As a prerequisite to understand a possible functional role of the monoaminergic neurotransmitters, the serotonergic, noradrenergic, and dopaminergic innervation of the optic tectum as well as the distribution of serotonin 2A receptors, the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and calbindin D-28K was studied in domestic chicks by immunohistochemical techniques. Serotonergic, noradrenergic, and tyrosine hydroxylase positive axons and axon terminals were present in all layers of the optic tectum. Generally, the highest densities of serotonergic, noradrenergic, and tyrosine hydroxylase positive fibers were found in the superficial tectal layers 1-8, whereas only moderate densities of serotonergic, noradrenergic, and tyrosine hydroxylase positive fibers became obvious in the deep tectal layers 9-15. Serotonergic fibers were particularly abundant in layers 4, 5a and 7 and serotonin 2A receptors in layer 13. Noradrenergic fibers were densest in layers 4 and 5a, whereas tyrosine hydroxylase positive fibers showed a slightly different distribution pattern with additional dense labeling in layer 7. As revealed by double-labeling immunohistochemistry, serotonergic fibers were closely related to the cell bodies of calbindin-positive horizontal cells in layer 5b and tyrosine hydroxylase positive fibers often contacted DARPP-32+ dendritic shafts in layers 9 and 10. These findings indicate that the catecholaminergic innervation of the optic tectum consists of a noradrenergic and a dopaminergic component and that the noradrenergic, serotonergic, and dopaminergic system may be potentially involved in the modulation of retinal input in the superficial layers of the optic tectum as well as in the modulation of tectal output via the deep tectal layers.

Proximal composition and fatty acid profile of Hemigrapsus crenulatus (H. Milne Edwards, 1837) as one of the main foods of "patagonian blenny"Eleginops maclovinus (Cuvier, 1830) / Composição proximal e perfil de ácidos graxos de Hemigrapsus crenulatus (H. Milne Edwards, 1837) como um dos principais alimentos da "blenny patagônica" Eleginops maclovinus (Cuvier, 1830)

Abstract The Patagonian blenny (Eleginops maclovinus) is species endemic to South America with physiological characteristics that would facilitate its incorporation into Chilean aquaculture. However, there is currently no specific artificial food that can be used to raise E. maclovinus. In light of this problem, this study describes the proximal composition and fatty acid profile of the crab Hemigrapsus crenulatus, one of the main foods of E. maclovinus. The purpose of the study is to serve as basic information for the development of a specific artificial diet for juveniles of this fish species. The proximal analysis of the complete body of H. crenulatus indicates that it is mainly composed of ash (35.9%), proteins (32.2%), glucides (19.8%) and minor lipids (3.6%). The fatty acid profile is 40.7% PUFAs, 29.7% MUFAs and 29.5% SAFAs, and the most abundant acids are Eicosapentaenoic (18.8%), Oleic (6.8%) and Palmitic (16.6%), respectively. H. crenulatus has highest level of proteins, lipids and PUFAs among the species of the Brachyura infraorder.

Resumo O "blenny da patagônia" (Eleginops maclovinus) é uma espécie endêmica da América do Sul, com características fisiológicas que facilitariam sua incorporação na aquicultura chilena. No entanto, atualmente não há alimento artificial específico que possa ser usado para criar E. maclovinus. Diante desse problema, este estudo descreve a composição proximal e o perfil de ácidos graxos do caranguejo Hemigrapsus crenulatus, um dos principais alimentos de E. maclovinus. O objetivo do estudo é servir como informação básica para o desenvolvimento de uma dieta artificial específica para espécies juvenis desse peixe. A análise proximal do corpo completo de H. crenulatus indica que ele é composto, principalmente, de cinzas (35,9%), proteínas (32,2%), glicídios (19,8%) e lipídios menores (3,6%). O perfil de ácidos graxos é 40,7% PUFA, 29,7% MUFA e 29,5% SAFA, e os ácidos mais abundantes são eicosapentaenoico (18,8%), oleico (6,8%) e palmítico (16,6%), respectivamente. H. crenulatus possui o mais alto nível de proteínas, lipídios e PUFAs entre as espécies da infraordem de Brachyura.

Características antropométricas y somatotipo en seleccionados chilenos de remo / Anthropometric characteristics and somatotype in elite Chilean rowers

El objetivo del estudio fue describir las características antropométricas y somatotipo de los seleccionados chilenos de remo. Se evaluaron a 21 deportistas (6 mujeres y 15 hombres) con edades promedio de 18,66 ± 2,58 años para las mujeres y de 22,06 ± 4,71 años para los hombres. El estudio se realizó previo al clasificatorio Panamericano Lima 2019, al momento de las evaluaciones, los deportistas se encontraban concentrados en el centro de entrenamiento olímpico (CEO) ubicado en Curauma en la región de Valparaíso en Chile. Las evaluaciones antropométricas se realizaron en base al perfil restringido de 25 variables propuesto por Ross & Kerr (1991), que permitió fraccionar la masa corporal en 5 componentes (tejidos: piel, residual, óseo, adiposo y muscular). Se midieron también la envergadura, la altura ilioespinal y los pliegues del bíceps y supracrestídeo, todas las medidas se realizaron en base al protocolo de marcaje y evaluación propuesto por ISAK. Se uso el método de Carter y Heath para calcular el somatotipo, describiendo los componentes de endomorfía, mesomorfía y ectomorfía respectivamente. Los resultados mostraron un porcentaje de grasa en hombres de 19,34 ± 1,59 % y en mujeres de 27,08 ± 3,6 % (p=0,003), la masa muscular de hombres fue de 52,69 ± 1,78 % y en mujeres de 45,68 ± 4,19 % (p=0,003), se apreció un somatotipo mesomorfo balanceado tanto en hombres (1,7-5,3-2,2) como mujeres (2,5-3,7-2,7). Se concluye que los seleccionados chilenos de remo presentan un alto desarrollo de masa muscular y un bajo porcentaje de masa grasa, además de un somatotipo mesomorfo balanceado.

The aim of the study was to describe the anthropometric characteristics and somatotype of the Chilean selected rowers. Twenty one 21 athletes (6 women and 15 men) with an average age of 18.66 ± 2.58 years for women and 22.06 ± 4.71 years for men were evaluated. The study was conducted prior to the Pan American qualification in Lima 2019. At the time of the evaluations, the athletes were concentrated in the Olympic Training Center (CEO) located in Curauma in the Valparaíso region of Chile. The anthropometric evaluations were carried out based on the restricted profile of 25 variables proposed by Kerr and Ross that allowed the fractionation of the body mass into 5 components (tissue: skin, residual, bone, adipose and muscle). The wingspan, the iliospinal height and the folds of the biceps and supracrestide were also measured; all measurements were based on the protocol of marking and evaluation proposed by ISAK. Carter and Heath method was used to calculate the somatotype, describing the components of endomorphy, mesomorphy and ectomorphy respectively. The results showed a percentage of fat in men of 19.34 ± 1.59 % and in women of 27.08 ± 3.6 % (p = 0.003), the muscle mass of men was 52.69 ± 1.78 % and in women of 45.68 ± 4.19 % (p = 0.003), a balanced mesomorphic somatotype was observed in both men (1.7-5.3-2.2) and women (2.5-3, 7-2.7). It is concluded that the Chilean rowing selected have a high development of muscle mass and a low percentage of fat mass, in addition to a balanced mesomorphic somatotype.

Innervation of orbital and choroidal blood vessels by the pterygopalatine ganglion in pigeons.

Orbital and choroidal blood vessels in mammals are known to receive a parasympathetic innervation from the pterygopalatine ganglion, which appears to utilize vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) to increase choroidal blood flow. The present studies were undertaken to elucidate the anatomical and neurotransmitter organization of the pterygopalatine ganglion input to orbital and choroidal blood vessels in pigeons. Single- or double-label immunohistochemistry were employed on paraformaldehyde-fixed cryostat sections of the pigeon eye and surrounding orbital tissue to localize 1) VIP+ neurons and fibers; 2) choline acetyltransferase (CHAT)-containing cholinergic neurons and fibers; 3) axons containing the 3A10 neurofilament-associated antigen; and 4) neuronal NO synthase (nNOS)-containing neurons and fibers. NOS+ neurons and fibers were also identified by NADPH-diaphorase histochemistry in sections and whole-mount specimens. The pterygopalatine ganglion was found to consist of an interconnected series of three to four main microganglia of about 50-200 neurons each and numerous lesser microganglia. The major microganglia of the pterygopalatine network in pigeon lie along the superior aspect of the Harderian gland, with many additional fibers and microganglia of the network encircling the gland. Neurons of all microganglia were extremely rich in VIP, nNOS, and NADPH-diaphorase and moderate in CHAT. The majority of the pterygopalatine ganglion neurons were observed to co-contain VIP and nNOS. Axons labeled for VIP, nNOS, NADPH-diaphorase, or the 3A10 antigen could be traced from the pterygopalatine ganglion network to perivascular fiber plexi on orbital blood vessels. These orbital vessels, many of which enter the choroid posteriorly and nasally, appear to be a conduit by which pterygopalatine postganglionic fibers reach the choroid. The pterygopalatine postganglionic fibers were also seen to innervate the Harderian gland and contribute branches to the nearby ophthalmic nerve. Within the choroid, VIP+ fibers were widely scattered and sparse but were most abundant in nasal choroid. A few VIP+ and NADPH- diaphorase+ neurons were also observed in the choroid. These results suggest that pterygopalatine ganglion neurons of birds use VIP and NO to exert vasodilatory control over blood flow to and within the avian choroid.

Leukemic transformation in patients with the 5q- alteration: analysis of the behavior of the 5q- clones in preleukemic to leukemic phases.

Serial cytogenetic studies have been performed in four patients with myelodysplastic syndromes. In all four a 5q- alteration was present, but with a different pattern of presentation. One patient presented 5q- as the only alteration since diagnosis; two patients acquired this alteration during the course of the disease; and the fourth showed a 5q- plus other alterations since the first cytogenetic study. Likewise, three of the four patients showed a clone with trisomy 8 and without 5q-. According to these observations and others from the literature with similar cytogenetic behavior, we have analyzed the following points: 5q- as a primary event and as the only alteration, 5q- as a secondary event, 5q- plus other alterations, and presence of cytogenetically different clones. Analysis of these points suggests that the 5q- alteration can represent an early mutation conferring a slow capacity of expansion to the affected clones, with the possibility of cytogenetic evolution during the progression of the disease (about 30% of the patients). Likewise, the association of trisomy 8 clones with 5q- clones can be a nonrandom event.

Serotonergic afferents of the pigeon accessory optic nucleus.

Injections of a retrograde tracer into the accessory optic nucleus of the basal optic root (nBOR) of the pigeon, combined with 5-HT immunochemistry, revealed that serotonergic projections to the nBOR appeared to originate mainly from the median (MR) and paramedian (PMR) raphe nuclei. These projections were confirmed by the significant decrease in 5-HT immunoreactivity observed in nBOR after lesions in MR and PMR. These data characterize distinct sources of 5-HT innervation to the pigeon nBOR and suggest that those afferents could represent part of a modulatory system that contributes to the role of the nBOR in optokinetic mechanisms.

Serum hyaluronic acid as a comprehensive marker to assess severity of liver disease in schistosomiasis.

Schistosomiasis mansoni is a non-cirrhotic fibrogenic disease model. The mild form shows normal liver function with slight or no liver fibrosis whereas in the periportal fibrosis form the manifestations of portal hypertension prevail over hepatocellular failure. We assessed serum hyaluronic acid as a marker of the course of the disease. We studied 24 patients presenting with pure chronic forms of schistosomiasis and seven with cirrhosis. In order to measure serum hyaluronic acid we developed a sandwich fluorescent ELISA-like assay. alpha2-Macroglobulin, prothrombin index, gamma-glutamyltransferase, platelets and ultrasound parameters were also assessed. The 20 micro g/l (ROC plot) hyaluronic acid level differentiated patients with the mild form (with no portal hypertension) from those with the severe form of schistosomiasis with 78% diagnostic efficacy. The 80 micro g/l cut-off value differentiated patients with the severe form of schistosomiasis from the cirrhotic group with similar diagnostic efficacy. alpha2-Macroglobulin provided no distinction between the groups studied. The hyaluronic acid serum concentration correlated positively with the splenic vein diameter (P=0.004) and marginally with alpha2-macroglobulin (P=0.059). Serum hyaluronic acid is a good marker for the initial phase of hepatic fibrosis and it was able to assess severity of liver disease in schistosomiasis.

A pharmacokinetic study to determine the drug interaction between valproate and propranolol.

A 40-year-old female receiving divalproex sodium (VPA) monotherapy for epilepsy developed a tremor secondary to the drug. Propranolol treatment was initiated. While receiving propranolol 40 mg, VPA clearance was reduced from 1.66 L/hr to 1.19 L/hr and dropped to 1.08 L/hr on propranolol 80 mg. The mechanism of this interaction is unknown. To evaluate the potential for a drug interaction between these two agents, 12 patients on VPA monotherapy, ages 19-55, were studied. The subjects were maintained on a constant dose of VPA. Each was then randomly assigned to receive placebo, or long-acting propranolol 60 mg/day or 120 mg/day. Mean VPA serum concentrations did not change among the three groups. Plasma half-life of VPA ranged from 7.3-18 hours and did not change with coadministration of propranolol. We concluded that VFA metabolism is not affected by coadministration of propranolol in this group of patients.

Pharmacokinetics and muscle histopathology of intramuscular valproate.

To determine the safety and pharmacokinetics of parenteral sodium valproate healthy mature greyhound dogs, were given intramuscular injections following intravenous injections. Dosings intravenously and intramuscularly were at 20, 40 and 60 mg/kg in the three groups. Intravenous infusion rates were constant. Sodium valproate solution concentrations of 300, 400 and 500 mg/ml were administered. Intramuscular valproate was quickly absorbed. Bio-availability approached 70%. Half life of 120 min was calculated. Toxic muscle necrosis was observed at all concentrations. Dosing valproate intramuscularly in humans is problematic in view of the muscle damage. Despite tissue damage sodium valproate was well absorbed intramuscularly. The intravenous injection of valproate at high concentrations, large doses and fast infusion rates produced no evidence of cardiotoxicity and levels of 180 micrograms/ml.

Plasma-kallikrein clearance by the liver of acetaminophen-intoxicated rats.

The liver synthesizes prokallikrein and is the main organ to clear the active enzyme (plasma-kallikrein) from circulation. This clearance, a receptor-mediated endocytosis, is calcium-independent and not affected by the blockade of Kupffer cells. The effects of endothelial cells blockade and of acetaminophen intoxication on the clearance of 10 nM rat plasma-kallikrein (RPK) by the isolated, exsanguinated and perfused rat liver are now reported. Endothelial cells blockade obtained by the addition of large excess (30 uM) of formaldehyde-treated serum albumin to the perfusion fluid does not affect the hepatic clearance of RPK (the half-lives of hepatic uptake were 15.5 +/- 1.0 min in the absence versus 16.5 +/- 1.4 min in the presence of the treated protein, p > 0.05). Some livers were perfused 24 hours after acetaminophen intoxication: 6.6 mmol/kg given i.p. after a 42-hour period of fast. Hepatocyte injury suggested by elevated aminotransferase activity (ALT 10 times control value, AST 30 times control value), acute phase inflammatory response (serum alpha 2-macroglobulin increase) and reduced synthetic function (serum albumin decrease), was confirmed histologically and only zone 3 hepatocytes were necrotic. A 66-hour period of fast does not affect by itself the hepatic clearance of RPK (16.9 +/- 1.3 min of half-life of hepatic uptake) when compared with the control group (15.5 +/- 1.0 min, p > 0.05). On the other hand the RPK clearance by the livers of rats previously intoxicated with acetaminophen was markedly deficient (the half-life of hepatic uptake was 39.2 +/- 3.2 min). These findings suggest that RPK is internalized by hepatocytes, preferentially by those of the perivenular zone of the hepatic acinus.