Brain MR Imaging of Patients with Perinatal Chikungunya Virus Infection.

Since 2005, it has been known that mother-to-child transmission of the chikungunya virus is possible. Transmission generally occurs in the perinatal period. In the present study, we describe the brain lesions seen on MR imaging of 6 cases of perinatal chikungunya infection. Patients who underwent brain MR imaging in the acute phase presented with areas of restricted diffusion in the white matter, suggesting a perivascular distribution, whereas those in the subacute/late phase showed cystic lesions, also with a perivascular distribution, with or without brain atrophy. One patient also presented with scattered hemorrhages in the frontal and parietal lobes. Important differential diagnoses include rotavirus, Parechovirus, herpes simplex infection, and hypoxic-ischemic encephalopathy, depending on the disease phase.

Neurogenic bladder in the settings of congenital Zika syndrome: a confirmed and unknown condition for urologists.

INTRODUCTION: Congenital Zika syndrome (CZS) is a recently discovered condition that affects central nervous system structures that control the lower urinary tract. The first cases of neurogenic bladder (NB) were recently reported as a sequalae of CZS in neurologically impaired children. OBJECTIVE: Our goal is to further evaluate NB in the setting of CZS, identifying urological risk indicators in hopes that early diagnosis will mitigate the impact of the disease. STUDY DESIGN: Urological assessment was performed in all patients with CZS and neurological impairment who were referred to our urodynamic clinic between June 2016 and May 2018. Neurogenic bladder was confirmed by urodynamic evaluation, and urological risk was based on urodynamic results. RESULTS: Sixty-nine patients with CZS were tested. The majority (63 patients, 91.3%) presented with overactive bladder with increased pressures and reduced capacity for age (table 1). Different urodynamic patterns were observed, and the association of reduced bladder capacity for age, high bladder-filling pressure, and increased postvoid residual were frequently observed. DISCUSSION: NB continues to be consistently diagnosed in our cohort of CZS, mostly with high-risk indicators for renal impairment. When not intervened upon in a timely manner, NB can cause progressive damage to the urinary tract, but the lack of knowledge that CZS causes NB delays investigation and treatment. Parents and health professionals will need to be sensitized to the risks that ZIKV can pose to the urinary tract so that appropriate therapies are initiated to prevent irreversible renal damage. CONCLUSION: NB is a common condition among our patients with CZS and microcephaly. This is a new cause of NB, unknown to urologists. While further investigation is necessary to understand long-term disease behavior and therapeutic response, increased knowledge among urologists may help to reduce morbidity related to untreated NB and to mitigate the disease burden for patients and families.

Antioedematogenic activity, acetylcholinesterase inhibition and antimicrobial properties of Jacaranda oxyphylla.

Jacaranda oxyphylla Cham. (Bignoniaceae) is a shrub found in the Brazilian cerrado and used in folk medicine to treat microbial infections. The aim of this study was to carry out a phytochemical screening and evaluate antioedematogenic, antimicrobial and antiacetylcholinesterase properties of J. oxyphylla crude extracts. All extracts analysed showed presence of terpenoids, which are potentially active chemical substances. A high AChE inhibitory activity for hexane extract from leaves and for the extracts from twigs was found. Ethanol extract from leaves of J. oxyphylla showed activity against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria. This extract was also effective in inhibiting the stages of inflammation evaluated. Biological investigation and phytochemical screening of J. oxyphylla extracts provided additional evidence of its traditional medicinal value.

A putative role for inosine 5' monophosphate dehydrogenase (IMPDH) in Leishmania amazonensis programmed cell death.

Leishmania amazonensis undergoes apoptosis-like programmed cell death (PCD) under heat shock conditions. We identified a potential role for inosine 5' monophosphate dehydrogenase (IMPDH) in L. amazonensis PCD. Trypanosomatids do not have a "de novo" purine synthesis pathway, relying on the salvage pathway for survival. IMPDH, a key enzyme in the purine nucleotide pathway, is related to cell growth and apoptosis. Since guanine nucleotide depletion triggers cell cycle arrest and apoptosis in several organisms we analyzed the correlation between IMPDH and apoptosis-like death in L. amazonensis. The L. amazonensis IMPDH inhibition effect on PCD was evaluated through gene expression analysis, mitochondrial depolarization and detection of Annexin-V labeled parasites. We demonstrated a down-regulation of impdh expression under heat shock treatment, which mimics the natural mammalian host infection. Also, IMPDH inhibitors ribavirin and mycophenolic acid (MPA) prevented cell growth and generated an apoptosis-like phenotype in sub-populations of L. amazonensis promastigotes. Our results are in accordance with previous results showing that a subpopulation of parasites undergoes apoptosis-like cell death in the nutrient poor environment of the vector gut. Here, we suggest the involvement of purine metabolism in previously observed apoptosis-like cell death during Leishmania infection.

Anti-inflammatory and cicatrizing activities of a carbohydrate fraction isolated from sugary kefir.

Kefir is an association of microrganisms generally grown in milk, with known probiotic activities identified from its soured suspensions. Aqueous media are also able to grow kefir, but little is known about the probiotic properties of its fermented products. This work aimed to evaluate some probiotic properties of a carbohydrate fraction isolated from sugary kefir (sugary kefir carbohydrate [SKC]). Anti-inflammatory activity of the isolated fraction of carbohydrate was tested both in vitro (cellular respirometry and macrophage culture) and in vivo (50% effective dose, rat paw edema, vascular permeability, and cicatrizing test). The results indicated no significant difference for oxygen uptake or macrophage culture between control and test groups. Rat paw edema, however, showed a significant inhibitory activity by 30 +/- 4% and 54 +/- 8% (P < .001) for carrageenan and dextran, respectively. In the cicatrizing test, animals treated with SKC cream also presented less trauma after treatments as compared to the negative control group (P < .05). The overall data suggested the SKC as a natural product that could be used as a constituent of an anti-inflammatory compound.

Effect of light reduction on the incidence of retinopathy of prematurity.

The effect of ocular protection on the incidence of retinopathy of prematurity was tested in 188 newborns weighing less than 1600 g in a randomised controlled trial. No effect of ambient light reduction on the incidence of retinopathy of prematurity was shown.

Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.

Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane - an early hallmark of apoptosis - and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.

Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity.

Programmed cell death by apoptosis of unnecessary or potentially harmful cells is clearly beneficial to multicellular organisms. Proper functioning of such a program demands that the removal of dying cells proceed without an inflammatory reaction. Phosphatidylserine (PS) is one of the ligands displayed by apoptotic cells that participates in their noninflammatory removal when recognized by neighboring phagocytes. PS ligation induces the release of transforming growth factor-beta (TGF-beta), an antiinflammatory cytokine that mediates the suppression of macrophage-mediated inflammation. In Hydra vulgaris, an organism that stands at the base of metazoan evolution, the selective advantage provided by apoptosis lies in the fact that Hydra can survive recycling apoptotic cells by phagocytosis. In unicellular organisms, it has been proposed that altruistic death benefits clonal populations of yeasts and trypanosomatids. Now we show that advantageous features of the apoptotic process can operate without death as the necessary outcome. Leishmania spp are able to evade the killing activity of phagocytes and establish themselves as obligate intracellular parasites. Amastigotes, responsible for disease propagation, similar to apoptotic cells, inhibit macrophage activity by exposing PS. Exposed PS participates in amastigote internalization. Recognition of this moiety by macrophages induces TGF-beta secretion and IL-10 synthesis, inhibits NO production, and increases susceptibility to intracellular leishmanial growth.

Social violence: a case for classification as a sub-phenomenon of community in the ICNP.

The study is intended to illustrate that the nursing phenomenon, Violence, exists as a phenomenon of the aggregate and should thus be classified, under the higher level phenomenon, Community, in the International Classification for Nursing Practice (ICNP), published by the International Council of Nurses. This proposition was confirmed during a meeting of an international team of psychiatric nurses to plan reality-based postgraduate modules for the nine countries they represented. Substantiating data, based on the team's module, Violence, clinical investigation and a review of the literature, evolved from a classroom project in north-east Brazil. The Master's Degree nursing students conducted observations and interviews based on identified factors of the phenomenon on children in two municipal day-care centres in targeted neighbourhoods in João Pessoa, Paraíba, Brazil. Data were gleaned from observations and verbalizations regarding their individual drawings depicting sadness and happiness, from school records and observations of these children by their teachers. The data, evolving from the time-limited classroom project, are too sparse to be considered valid, but pave the road for further studies. Professional and lay-literature substantiates the occurrence of violence in the Brazilian society.

Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins.

PURPOSE: Neutrophils are implicated in the physiopathologic alterations of hemorrhagic cystitis (HC). Thus, we decided to test the antiinflammatory activity of glucose-mannose binding lectins extracted from D. violacea and D. guianensis seeds, which showed an inhibitory effect upon neutrophil migration in a model of rat peritonitis based on HC experimentally induced by cyclophosphamide (CYP). MATERIALS AND METHODS: Mice were treated with mesna (40 mg./kg., i.p.), lectins (1 and 10 mg./kg., i.v.) and 0.1 M of alpha-D-methyl-mannoside (alpha-CH3) or alpha-D-galactose (alpha-D-gal). The HC was induced by CYP (200 mg./kg., i.p.). The results were evaluated 12 hours after HC induction, based on the following parameters: vesical edema measurements, macroscopic and microscopic analysis of the bladders (Gray's analysis). The vesical edema was quantified either by the increase in bladder wet weight or by the determination of vesical vascular permeability (Evans' blue leakage). RESULTS: CYP-induced vesical edema was prevented by mesna and lectin treatment. The lectin effects were dose-dependent, and at the highest dose were similar to that achieved by mesna treatment. alpha-CH3 selectively reversed the lectin inhibitory effect. Histopathological analysis corroborated these findings and showed an intense reduction of leukocyte infiltration and tissue damage by lectin treatment. The bladders from the mesna-treated group showed a nearly normal histological pattern. However, differently from this group, none of the lectins abolished CYP-induced hemorrhage. CONCLUSIONS: The glucose-mannose binding lectins showed strong antiinflammatory activity in the mouse model of HC induced by CYP. As lectins mainly affected leukocyte vesical infiltration, we suggest a competitive blockage of glucosylated (mannose-glucose) selectin binding sites by lectins.

Heat shock induction of apoptosis in promastigotes of the unicellular organism Leishmania (Leishmania) amazonensis.

Apoptosis and/or programmed cell death have been described in examples ranging from fungi to man as gene-regulated processes with roles in cell and tissue physiopathology. These processes require the operation of an intercellular communicating network able to deliver alternative signals for cells with different fates and is thus considered a prerogative of multicellular organisms. Promastigotes from Leishmania (Leishmania) amazonensis, when shifted from their optimal in vitro growth temperature (22 degrees C) to the temperature of the mammalian host (37 degrees C), die by a calcium-modulated mechanism. More parasites die in the presence of this ion than in its absence, as detected by a colorimetric assay based on the activity of mitochondrial and cytoplasmic dehydrogenases which measures cell death, independently of the process by which it occurs. A heat shock, unable to induce detectable parasite death (34 degrees C for 1 h), is able to significantly raise the concentration of intracellular free calcium in these cells. Heat-shocked parasites present ultrastructural and molecular features characteristic of cells dying by apoptosis. Morphological changes, observed only in the presence of calcium, are mainly nuclear. Cytoplasmic organelles are preserved. Heat shock is also able to induce DNA cleavage into an oligonucleosomal ladder detected in agarose gels by ethidium bromide staining and autoradiography of [alpha 32P]ddATP-labeled fragments. These results indicate that death by apoptosis is not exclusive of multicellular organisms.

[Nitric oxide in the treatment of neonatal pulmonary hypertension]. / Oxido nítrico no tratamento da hipertensão pulmonar persistente do recém-nascido.

This study describes the effects of nitric oxide in newborns with persistent pulmonary hypertension. We studied 9 infants with severe respiratory failure characterized by hypoxemia and pulmonary hypertension. All infants met ECMO criteria and the oxygenation index (OI) was greater than 25. Mean birth weight was 2698 -/+ 661 g and gestational age was 36.4 -/+ 2.6 weeks. Nitric oxide was administered in a Y circuit in the inspiratory line of the mechanical ventilator. Nitric oxide and NO2 concentrations were monitored with electrochemical analyzers (PACI and PACII-Draeger). Pulmonary hypertension was diagnosed with clinical and echocardiografic criteria, with detection of right to left shunt with color doppler. All patients showed a dramatic improvement in oxigenation after nitric oxide administration. The drug reduced the mean OI, which was 48.5 before its administration, to 17.7 after 30', 14.1 after 6 hours, and 10.5 after 12 hours. We observed in all patients a reduction in pulmonary vascular resistance, reversal of the right to left shunt without any effects on systemic arterial pressure. Metahemoglobin levels did not reach 1.5% in any patient. Only one out of the 9 patients died, after reversal of the pulmonary hypertension, from other complications of perinatal asphyxia. Our data show that nitric oxide is a promising drug in the treatment of neonatal pulmonary hypertension and that it may reduce the need of ECMO in severe respiratory failure.

Cellular response of protozoan parasites to host-derived cytokines.

Cytokines are extracellular signalling molecules, produced by different cell types and displaying a wide range of activities such as the induction or inhibition of target cell survival, proliferation and differentiation. When directly interacting with different parasites, cytokines exert similar activities, acting as growth factors and, in one of the examples given here, also enhancing parasite survival. The importance of this interaction in the natural history of parasitic diseases as well as the selective forces maintaining functional cytokine 'receptors' in protozoan parasites is discussed in this review by Marcello Barcinski and Maria Elisabete Costa-Moreira.

Granulocyte-macrophage colony-stimulating factor increases the infectivity of Leishmania amazonensis by protecting promastigotes from heat-induced death.

We have studied the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the infectivity of promastigotes of Leishmania amazonensis, an obligate intramacrophage parasite. We measured the capacity of the promastigotes to infect macrophages after preincubation at different temperatures (28, 34, and 37 degrees C) with recombinant murine GM-CSF, as well as the effect of an anti-murine GM-CSF antibody on the in vitro and in vivo infectivity of the parasite. GM-CSF increases the capacity of the promastigotes to infect cells when preincubated at 34 and 37 degrees C, whereas the anti-GM-CSF antibody exerts the opposite effect: it decreases the internalization rate and the progression of infection in macrophage cultures and slows the growth of the lesion in infected BALB/c mice. Neither of the described effects were observed when the in vitro and in vivo infections were made with amastigotes. Promastigotes die in a time-dependent manner when incubated at temperatures higher than 28 degrees C in the absence of GM-CSF. They are protected from this heat-induced death by incubation with the recombinant hormone. Our interpretation of these data is that the increase in the infectivity of promastigotes when incubated with GM-CSF at the temperatures at which infection occurs (34 and 37 degrees C) is due to the larger number of surviving forms within the infecting population. The decrease in infectivity when they are incubated with the antibody is due to inhibition of the protection conferred by the GM-CSF produced by the macrophages during the in vitro and in vivo infections.

A pratica de prescricao ambulatorial de antidepressivos

Os autores investigam a pratica de prescricao de antidepressivos triciclios em um ambulatorios de saude mental da rede publica em campinas-SP. Verificam que para 72 por cento dos pacientes foram prescritas drogas em subdosagem, a 74 por cento por tempo inferior ao recomendado e a 63 por cento em associaçao com outros psicotropicos, principalmente benzodiazepinicos. Concluem pela inadequaçao desta pratica e pelo risco que acarreta em termos da cronificaçao dos quadros depressivos. Sugerem a criaçao de programas especificos para treinamento da equipe em diagnostico e tratamento adequado de pacientes deprimidos.