DNA as a perfect quantum computer based on the quantum physics principles.

DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic multiscale nature requires chemistry and quantum physics to understand the structure and quantum informatics to explain its operation as a perfect quantum computer. Here, we present theoretical results of DNA that allow a better description of its structure and the operation process in the transmission, coding, and decoding of genetic information. Aromaticity is explained by the oscillatory resonant quantum state of correlated electron and hole pairs due to the quantized molecular vibrational energy acting as an attractive force. The correlated pairs form a supercurrent in the nitrogenous bases in a single band π -molecular orbital ( π -MO). The MO wave function ( Φ ) is assumed to be the linear combination of the n constituent atomic orbitals. The central Hydrogen bond between Adenine (A) and Thymine (T) or Guanine (G) and Cytosine (C) functions like an ideal Josephson Junction. The approach of a Josephson Effect between two superconductors is correctly described, as well as the condensation of the nitrogenous bases to obtain the two entangled quantum states that form the qubit. Combining the quantum state of the composite system with the classical information, RNA polymerase teleports one of the four Bell states. DNA is a perfect quantum computer.

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus

Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.

Decreased muscle strength is associated with proinflammatory cytokines but not testosterone levels in men with diabetes

The aim of this study was to compare muscle strength in male subjects with type 2 diabetes mellitus (DM2) with and without low plasma testosterone levels and assess the relationship between muscle strength, testosterone levels, and proinflammatory cytokines. Males (75) aged between 18 and 65 years were divided into 3 groups: control group that did not have diabetes and had a normal testosterone plasma level (>250 ng/dL), DnormalTT group that had DM2 with normal testosterone levels, and the DlowTT group that had DM2 and low plasma testosterone levels (<250 ng/dL). The age (means±SD) of the groups was 48.4±10, 52.6±7, and 54.6±7 years, respectively. Isokinetic concentric and isometric torque of knee flexors and extensors were analyzed by an isokinetic dynamometer. Plasma testosterone and proinflammatory cytokine levels were determined by chemiluminescence and ELISA, respectively. Glycemic control was analyzed by glycated hemoglobin (HbA1C). In general, concentric and isometric torques were lower and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β plasma levels were higher in the groups with diabetes than in controls. There was no correlation between testosterone level and knee torques or proinflammatory cytokines. Concentric and isometric knee flexion and extension torque were negatively correlated with TNF-α, IL-6, and HbA1C. IL-6 and TNF-α were positively correlated with HbA1C. The results of this study demonstrated that muscle strength was not associated with testosterone levels in men with DM2. Low muscle strength was associated with inflammatory markers and poor glycemic control.

Frecuencia y resistencia antimicrobiana en Staphylococcus / Frequency and antimicrobial resistance in Staphylococcus

La presente investigación tuvo como objetivo establecer la frecuencia de aislamiento de las diferentes especies de estafilococos y determinar la resistencia antimicrobiana de las cepas aisladas. Se realizó un estudio retrospectivo, en cepas aisladas en el Centro de Referencia Bacteriológica del Servicio Autónomo Hospital Universitario de Maracaibo, durante el período enero 2011 ­ diciembre 2015. Se obtuvo un porcentaje de aislamiento para S. aureus del 61,36% y 38,64% para coagulasa negativa, observándose mayor frecuencia de aislamiento en el área de hospitalización para ambos grupos de microorganismos. Las muestras de piel y tejidos blandos representaron las principales fuentes de aislamiento para S. aureus; mientras que para el grupo coagulasa negativa, fueron las muestras de sangre. Todas las cepas fueron sensibles a los glicopéptidos. La resistencia para los b-lactámicos fue acentuada para ambos grupos bacterianos, mostrando variabilidad para macrólidos y lincosamidas y para los restantes antibióticos probados, se encontraron bajos porcentajes de resistencia. Los resultados demuestran que S. aureus es la especie más frecuente del género; seguida de S. epidermidis y S. haemolyticus entre coagulasa negativa. Ambos grupos de microorganismos expresan fenotipos de resistencia a penicilina y eritromicina, sensibilidad a vancomicina y teicoplanina y susceptibilidad variable al resto de antibióticos evaluados.

The objective of the present investigation was to establish the frequency of isolation of the different species of staphylococci and to determine the antimicrobial resistance of the isolated strains. A retrospective study was carried out in isolated strains at the Bacteriological Reference Center of the Autonomous Service of the University Hospital of Maracaibo during the period January 2011 to December 2015. A percentage of isolation was obtained for S. aureus of 61.36% and 38,64% for coagulase negative, showing a higher frequency of isolation in the hospitalization area for both groups of microorganisms. Skin and soft tissue samples represented the main sources of isolation for S. aureus; while for the coagulase negative group, they were blood samples. All strains were sensitive to glycopeptides. Resistance for ß-lactams was accentuated for both bacterial groups, showing variability for macrolides and lincosamides and for the remaining antibiotics tested, low percentages of resistance were found. The results show that S. aureus is the most frequent species of the genus; followed by S. epidermidis and S. haemolyticus, among coagulase negative. Both groups of microorganism express phenotypes of resistance to penicillin and erythromycin, sensitivity to vancomycin and teicoplanin and variable susceptibility to the rest of evaluated antibiotics.

Ilex paraguariensis extracts extend the lifespan of Drosophila melanogaster fed a high-fat diet

Studies have suggested that total energy intake and diet composition affect lifespan and ageing. A high-fat diet induces oxidative stress and affects the development of diseases. In contrast, antioxidants are capable of reducing its harmful effects. Yerba mate beverages are an important source of antioxidants, but there is scarce knowledge about their effects on suppressing fat accumulation. Here, we investigated the compounds present in yerba mate extracts and assessed their effects on Drosophila melanogaster given a high cholesterol diet. LS-ESI-MS analysis showed the presence of matesaponins, phenolic compounds and methylxanthines in all of the examined extracts. In Drosophila, under extract treatment conditions, the mean lifespan was significantly extended from 38 to 43 days, there was an increase in the ability to support induced stress and decrease in lipid peroxidation products. Moreover, yerba mate extracts recovered the glutathione S-transferases (GST) activity and reduced the cholesterol level. Taken together, our results support that extracts can extend lifespan by reducing the detrimental effect of a high-fat diet in D. melanogaster, and this outcome can be associated with the compound content in the extracts. This study improves the understanding of natural interventions that reduce stress-induced oxidative damage, which is fundamental in promoting healthy ageing.

Cytokine profile and lymphocyte subsets in type 2 diabetes

Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

Epigenética de la endometriosis y su perspectiva terapéutica en el marco de un sistema integral de atención de la infertilidad: revisión y propuesta de investigación / Epigenetics of endometriosis and its therapeutic perspective in the framework of an integral system for infertility care: A review and research proposal / Epigenética da endometriose e sua perspectiva terapêutica no marco de um sistema integral de atenção da infertilidade: revisão e proposta de investigação

La endometriosis consiste en la presencia ectópica de glándulas endometriales y células estromales fuera de la cavidad uterina (principalmente en ovarios y superficies de órganos internos de la cavidad pélvica). Es uno de los desórdenes ginecológicos benignos más comunes en las mujeres que están en edad reproductiva. Hay diversas teorías para explicar la endometriosis. La más aceptada es la denominada "menstruación retrógrada". Las mujeres con endometriosis presentan dolor en la región pélvica-abdominal, dismenorrea, dispareunia, mucho sangrado en la menstruación, dolor pélvico no-menstrual, dolor al ovular, disquecia, disuria, fatiga crónica y sub-fertilidad. Diversos estudios han relacionado la endometriosis con aparición de cáncer ovárico, con un desarrollo de carcinomas en 5% - 10% de los casos de mujeres con endometriomas ováricos. El desarrollo efectivo de estrategias terapéuticas para el control de la endometriosis depende de una correcta identificación de los patrones epigenéticos y de genes candidatos, que serían el blanco en los tratamientos.

Endometriosis consists in the ectopic presence of endometrial glands and stromal cells outside the uterine cavity (mainly in ovaries and on the surface of internal organs of the pelvic cavity). It is one of the most common benign gynecological disorders in reproductive-age women. There are various theories to explain endometriosis. The most widely accepted theory is known as "retrograde menstruation". Common endometriosis symptoms include pelvic or abdominal pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, non-menstrual pelvic pain, ovulation pain, dyschezia, dysuria, chornic fatigue syndrome, and fertility problems. Various studies have associated endometriosis with the onset of ovarian cancer, with carcinoma development in 5 to 10% of women with ovarian endometriomas. The successful development of therapeutic strategies to control endometriosis depends on a correct identification of the epigenetic patterns and gene candidates to be targeted by treatment.

A endometriose consiste na presencia ectópica de glândulas endometriais e células estromais fora da cavidade uterina (principalmente em ovários e superfícies de órgãos internos da cavidade pélvica). É um dos desordens ginecológicos benignos mais comuns nas mulheres que estão em idade reprodutiva. Há diversas teorias para explicar a endometriose. A mais aceitada é a denominada "menstruação retrógrada". As mulheres com endometriose apresentam dor na região pélvica-abdominal, dismenorreia, dispareunia, muito sangrado na menstruação, dor pélvico não-menstrual, dor ao ovular, disquesia, disúria, fatiga crónica e subfertilidade. Diversos estudos hão relacionado a endometriose com aparição de câncer ovárico, com um desenvolvimento de carcinomas em 5% - 10% dos casos de mulheres com endometriomas ováricos. O desenvolvimento efetivo de estratégias terapêuticas para o controle da endometriose depende de uma correta identificação dos padrões epigenéticos e de genes candidatos, que seriam o alvo nos tratamentos.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3 vs 135.1±25.2, P=0.005), peak heart rate (HRpeak: 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO2peak: 24.2±3.2 vs 18.9±2.8, P<0.001), and anaerobic threshold (VO2VT: 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels.

Prevalence of metabolic syndrome and its association with educational inequalities among Brazilian adults: a population-based study

The present study estimated the prevalence of metabolic syndrome (MS) according to the criteria established by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) and analyzed the contribution of social factors in an adult urban population in the Southeastern region of Brazil. The sample plan was based on multistage probability sampling according to family head income and educational level. A random sample of 1116 subjects aged 30 to 79 years was studied. Participants answered a questionnaire about socio-demographic variables and medical history. Fasting capillary glucose (FCG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were determined and all non-diabetic subjects were submitted to the 75-g oral glucose tolerance test. Body mass index (BMI, kg/m²), waist circumference and blood pressure (BP) were determined. Age- and gender-adjusted prevalence of MS was 35.9 and 43.2 percent according to NCEP-ATPIII and IDF criteria, respectively. Substantial agreement was found between NCEP-ATPIII and IDF definitions. Low HDL-C levels and high BP were the most prevalent MS components according to NCEP-ATPIII criteria (76.3 and 59.2 percent, respectively). Considering the diagnostic criteria adopted, 13.5 percent of the subjects had diabetes and 9.7 percent had FCG ≥100 mg/dL. MS prevalence was significantly associated with age, skin color, BMI, and educational level. This cross-sectional population-based study in the Southeastern region of Brazil indicates that MS is highly prevalent and associated with an important social indicator, i.e., educational level. This result suggests that in developing countries health policy planning to reduce the risk of MS, in particular, should consider improvement in education.

Rendimiento productivo y características de la canal de corderos alimentados con dietas con diferentes niveles de torta de palma / Productive performance and carcass characteristics of lambs fed diets containing different levels of palm kernel cake

Objective. The objective of this study was to determine the effect on productive performance and carcass characteristics in lambs fed with different amounts of palm kernel cake. Material and methods. Thirty-two Santa Inês lambs, with an initial live body weight of 24.8 ± 3.59 kg were used. Treatments consisted of four levels (0; 6.5; 13.0 and 19.5%) of palm kernel cake added to the dry matter diet. Lambs were fed for 80 days, and then slaughtered to be evaluated for the quantitative characteristics of the carcass. Results. Intake of dry matter and non-structural carbohydrates decreased with increasing levels of palm kernel cake. The intake of neutral detergent fiber showed a linear increase. Crude protein and total digestive nutrient intake were not affected. Weight gain, and the feed:gain ratio of dry matter, organic matter, crude protein and total digestive nutrients were similar among the four treatments. There was an increase on the feed:gain ratio of neutral detergent fiber and a decrease of nonstructural carbohydrates. The weight gain at slaughter and biometric measures were not affected by treatment. The carcass compactness index showed a linear decrease. The indexes of leg muscularity, compactness of the leg and rib eye area were similar among treatments. There was a linear decrease in the cold carcass weight and commercial yield of the carcass. Conclusions. The diet made of up to 19.5% palm kernel cake reduced DM intake, the carcass compactness index and carcass commercial yield, but did not alter weight gain, or feed dry matter intake.

Liberación y seguimiento de dos grupos de tití gris (Saguinus leucopus) en el departamento de Tolima / Releasing and monitoring of two groups of white footed tamarins (Saguinus leucopus) in the region of Tolima

Este estudio fue realizado con dos grupos de tití gris (Saguinus leucopus), procedentes de decomisos y entregas voluntarias. Los animales fueron rehabilitados durante aproximadamente un año en la ciudad de Bogotá, con el fin de estimular el desarrollo y recuperación de las habilidades necesarias para su sobrevivencia al ser devueltos al medio ambiente natural. Se construyeron dos jaulas como plataformas de liberación en un bosque en el departamento del Tolima, y los animales fueron alojados en ellas para iniciar su proceso de acostumbramiento al medio. Durante este tiempo se realizó un estudio etológico, con el propósito de determinar las posibles variaciones comportamentales derivadas del cambio en el entorno. Los animales fueron liberados y se llevó a cabo el seguimiento visual para evaluar el proceso de rehabilitación y la adaptación de los individuos al nuevo hábitat. Se observó una variación en la presentación de comportamientos relacionados con actividades de desplazamiento, descanso e interacciones sociales en comparación con estudios realizados en cautiverio. Después de la liberación, los animales fueron vistos en sitios próximos a las jaulas de acostumbramiento, lo cual podría indicar que establecieron sus territorios en estas áreas; no se registraron variaciones significativas en la conformación de los grupos ni enfrentamientos entre las dos tropas. Estas observaciones indicarían que el proceso de liberación cumplió con su objetivo, y puede considerarse exitoso.

This study was carried out with two groups of white footed tamarins (Saguinus leucopus) from confiscations and voluntary incomes. Animals were rehabilitated during ayear in Bogotá, with the aim of developing and recovering abilities to survive in their natural environment. Two enclosures were built to the used as releasing platforms ina forest of Tolima region. Animals were put in these enclosures in order to begin the process of adaptation to the new environment. At that time researchers did an ethological study to determine behavioral variations due to the change of environment. Animals were released and monitored to evaluate the rehabilitation process and their adaptation. It was observed a variation on behavior related with activities of movement, resting and social interaction, comparing with captivity records. After releasing, animalswere seen in places close to the pre-releasing enclosures, and it could show thatthey established their territories in that areas. There was not significant variation in the conformation of groups and there were not records of fighting among troops. These observations could show that the process of release achieved its goal, and it could beconsidered successful.

Políticas públicas de medicamentos: trajetória e desafios / Public policies for medicines: trajectory and challenges

Por meio de um levantamento bibliográfico sobre as políticas públicas no setor de medicamentos brasileiro, o artigo examina as principais características das ações aplicadas na área, ressaltando seus resultados e deficiências, bem como as dificuldades encontradas para consolidar uma política de medicamentos no Brasil. O estudo realizado se fundamentou na análise de artigos por meio das bases de dados Scielo e Lilacs e de outras fontes. Desde a extinta Central de Medicamentos (CEME) até a aprovação da Política Nacional de Medicamentos (PNM), todas as ações e projetos foram voltados principalmente para a reorientação da Assistência Farmacêutica na atenção básica, garantindo, por conseguinte, o acesso e o uso racional dos medicamentos essenciais.

Through a bibliography review of public policies in Brazilian medicine sector, this paper examines the main characteristics of actions implemented in this area, lighting their results and deficiencies, as well as the difficulties to consolidate a policy for medicines in Brazil. The study is based on analysis of articles searched in the Scielo and Lilacs databases and other sources. Since the extinct Medicine Center to the approval of the National Medicine Policy, all the actions and programs aimed mainly at the reorientation of Pharmaceutical Assistance in primary health are, to guarantee access and rational use of essential medicines essential.

Efeito da inibição da óxido nítrico sintase induzível na capacitação in vitro de espermatozoides bovinos / Effect of inhibition of inducible nitric oxide synthase on in vitro capacitation of bovine spermatozoa

Avaliaram-se o papel do óxido nítrico (NO) por meio da inibição da enzima óxido nítrico sintase induzível (iNOS), após a adição da aminoguanidina (AG), na motilidade, no vigor e na integridade da membrana plasmática nos tempos de 15, 60, 120, 180, 240 e 300min e a atividade mitocondrial e a capacitação de espermatozoides bovinos após 300min de cultivo. Adicionaram-se diferentes concentrações (0,001, 0,01 e 0,1M) de AG durante a capacitação induzida pela heparina e 500μM de nitroprussiato de sódio (SNP, doador de NO) à concentração deletéria. A adição de 0,1M de AG diminuiu a motilidade e o vigor espermático e a integridade da membrana (P<0,05). A adição de SNP ao meio de cultivo com 0,1M de AG somente reverteu a integridade da membrana após 300min. A inibição da síntese de NO pela adição de AG não alterou a atividade mitocondrial. A percentagem de oócitos penetrados com espermatozoides tratados com 0,01 e 0,1M de AG diminuiu 20,3 e 100 por cento, respectivamente, em relação aos não tratados (controle) (P<0,05), contudo houve aumento de 15 por cento na percentagem de oócitos desnudados penetrados com espermatozoides capacitados em presença de 0,1M de AG. Conclui-se que a inibição da síntese de NO pela AG diminuiu a qualidade espermática durante a capacitação de espermatozoides bovinos in vitro, exceto a atividade mitocondrial. Somente a integridade da membrana foi revertida após adição de NO, sugerindo diferentes vias de ação do NO na qualidade espermática ao longo da capacitação in vitro de espermatozoides bovinos.

The role of nitric oxide (NO) was evaluated by inhibition of inducible nitric oxide synthase (iNOS), with aminoguanidine (AG) on motility, vigor, and plasmatic membrane integrity of bovine spermatozoa culture after 15, 60, 120, 180, 240, and 300min and on mitochondrial activity and capacitation after 300min, respectively. Different concentrations, 0.001, 0.01, and 0.1M of AG were added during the heparin induced capacitation and sodium nitroprusside (SNP, NO donor-500μM) to the deleterious concentration. The addition of 0.1M of AG diminished progressive motility, spermatic vigor, and membrane integrity (P<0.05). SNP addition to the 0.1M of AG did revert only plasmatic membrane integrity after 300min. Mitochondrial activity was not influenced by addition of AG. Percentage of penetrated oocytes after addition of 0.01 and 0.1M of AG diminished, 20.3 and 100 percent, respectively, in relation to the control oocytes (P<0.05). However, an increase of 15 percent was observed when denuded oocytes were used with 0.1M AG treated sperm (P<0.05). It was concluded that the inhibition of NO synthesis with aminoguanidine diminished sperm quality during in vitro capacitation of bovine spermatozoa, except the mitochondrial activity. Only membrane integrity was reverted with the addition of NO to culture medium, suggesting different pathways of NO action on bovine sperm quality during in vitro capacitation.

Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethasone-immunosuppressed Swiss mice

The in vivo antifungal activity of the naphthoquinone beta-lapachone against disseminated infection by Cryptococcus neoformans was investigated. Swiss mice were immunosuppressed daily with dexamethasone (0.5 mg per mouse) intraperitoneally for 3 days, the procedure was repeated 4 days later, and the animals were then challenged intravenously with C. neoformans (10(6) CFU/mL) 1 week later. Seven days after infection, the mice were divided into groups and treated daily with beta-lapachone (10 mg/kg, iv) for 7 (N = 6) and 14 days (N = 10). Amphotericin B (0.5 mg/kg) was used as comparator drug and an additional group received PBS. Treatment with beta-lapachone cleared the yeast from the spleen and liver, and the fungal burden decreased approximately 10(4) times in the lungs and brain 14 days after infection when compared to the PBS group (P < 0.05). This result was similar to that of the amphotericin B-treated group. Protection was suggestively due to in vivo antifungal activity of this drug and apparently not influenced by activation of the immune response, due to similar leukocyte cell counts among all groups. This study highlights the prospective use of beta-lapachone for treatment of disseminated cryptococcosis.

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises form an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The lightdark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

Atrial natriuretic peptide and feeding activity patterns in rats

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways.

Neutropenia febril en menores con Leucemia linfoblástica aguda / Febrile neutropenia in children with acute lymphoblastic leukemia (ALL)

Introducción: La neutropenia febril es la primera manifestación de una infección potencialmente letal en pacientes en quimioterapia por cáncer. Objetivo:Analizar el perfil de los episodios de neutropenia febril en pacientes menores de 15 años con diagnóstico de Leucemia Linfoblástica Aguda estudiados en Valdivia. Pacientes y método: Se analizaron 150 episodios de neutropenia febril en 47/51 menores de 15 años tratados según Protocolo de Leucemia Linfoblástica Infantil, PINDA 96 MINSAL, en el Hospital Clínico Regional de Valdivia (1996-1999). Resultados: La neutropenia fue severa: RAN < 500/mm3 en el 71,4% (107/150). Se estableció el foco de origen en el 72,6% (109/150), dado por patología respiratoria en el 53,4% (80/150). Se identificó el agente infeccioso en el 29,3% (44/150), con predominio de gram (+), seguido de gram (-) y hongos. Se determinó una infección del torrente sanguíneo en el 11,4% (17/150), de éstas el 47,1% se debió a bacilos gram (-), cocáceas gram (+) 35,3%, cándida sp 11,8%, bacilos gram (+) 5,8%. El tratamiento con Cloxacilina 100 mg/kg/día/ev + Amikacina 15 mg/kg/día/ev fue efectivo en el 66% (99/150) de los episodios. Aumentó al 94% (141/150) al agregarse Ceftriaxona 100 mg/kg/día ev. Conclusiones: Se obtuvo una adecuada identificación del foco infeccioso en pacientes neutropénicos febriles portadores de Leucemia Linfoblástica Aguda, lográndose su control con el esquema antibiótico utilizado.