Myelodysplastic syndrome progression to acute myeloid leukemia in a cat FeLV seroreactive

Background: Acute myeloid leukemia (AML) is a group of non-lymphoid hematological tumors characterized by aberrant proliferation and/or decreased apoptosis of a clone of non-mature cells, resulting in the accumulation of immature blast cells in the bone marrow and peripheral blood. It is considered rare, as it represents 10% of neoplasms of hematopoietic origin. However, it is known that felines seroreactive for FIV and FeLV are more predisposed and reports of this type of leukemia in cats in the literature are scarce. Thus, the objective of this study was to evaluate the blood and bone marrow of a cat seroreactive for FeLV that presented with myelodysplastic syndrome that progressed to acute myeloid leukemia. Case: A 6-year-old male mixed-breed cat, neutered, seroreactive for FeLV, showed apathy, weight loss, and pale mucous membranes. Initial peripheral blood smear evaluation revealed hypochromic normocytic anemia, leukopenia, neutropenia, lymphopenia, and thrombocytosis with many macropackets and giant platelets. Based on this blood picture, a long-spectrum antimicrobial therapy with amoxicillin and clavulanate [Clavulin® BD - 25 mg/kg, every 12 h] was started. Granulocyte colony stimulating factor used filgrastim (rHu G-CSF) [Fiprina® - 5 µg/kg, SC, every 48 h] and appetite stimulant mirtazapine [Mirtz® - 2 mg/cat, orally, every 48 h] were used to correct leukopenia and nutritional status, respectively. Follow-up blood smear evaluation on the 30th day showed persistence of the hematological changes noticed earlier. A bone marrow puncture was performed, and immunosuppressive therapy with prednisolone [Predsim® - 4 mg/kg, orally, every 24 h] was initiated. The aspirated material showed increased cellularity for age, decreased myeloid:erythroid ratio, and 39.8% of blasts of myeloid origin. An average of 17.7 megakaryocytes were observed per field (10x magnification). Bone marrow cytological evaluation suggested acute myeloid leukemia with dysmegakaryocytopoiesis. After the diagnosis, the examinations were repeated monthly, and there was still intense leukopenia. However, in view of the stable clinical status and leukopenia with neutropenia, treatment for leukemia was not instituted and only supportive treatment was administered when necessary. Eight months after the diagnosis, clinical status had worsened, and unlike the earlier hemograms, global leukocyte count had increased with predominant lymphocytosis (95% of the total leukocytes) with atypical lymphocytes. The cat died a few days later. Discussion: Bone marrow evaluation is indicated when peripheral blood cell abnormalities are present and cannot be explained in the context of the clinical history. In the present report, the bone marrow aspirate was hypercellular (cellularity above 75%); however, intense leukopenia was observed in the peripheral blood. In myelodysplastic syndromes, it is common for the bone marrow to be normal to hypercellular, which occurs when there is a greater production of myeloid or erythroid cell lines in response to the loss, destruction, or consumption of cells. Despite this, cytopenias may be present in the peripheral blood, since the defective cells undergo apoptosis and die before being released into the circulation, characterizing inefficient hematopoiesis. The diagnosis of acute leukemia comprises a variety of hematopoietic neoplasms that are complex and unique. Each acute leukemia subtype has defining characteristics that affect the prognosis and treatment of each animal.

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA+ e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA+.(AU)

The goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA+ cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA+ cells.(AU)

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA+ e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA+.(AU)

The goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA+ cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA+ cells.(AU)

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins / Identificação e susceptibilidade de isolados clínicos de Candida spp. para toxinas assassinas

Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.(AU)

Embora as infecções invasivas e a mortalidade causada por espécies de Candida estejam aumentando entre pacientes comprometidos, a resistência a agentes antifúngicos comuns também é um problema crescente. Analisamos 60 leveduras isoladas de pacientes com candidíase invasiva utilizando como estratégia PCR/RFLP baseada na região espaçadora transcrita interna (ITS2) para identificar diferentes espécies patogênicas de Candida. A análise por PCR foi realizada a partir de ADN genómico com um par de iniciadores da região ITS2-5.8S rDNA. As amostras PCR-positivas foram caracterizadas por RFLP. A restrição resultou em 23 isolados identificados como C. albicans usando AlwI, 24 isolados como C. parapsilosis usando RsaI e 13 como C. tropicalis usando XmaI. Em seguida, avaliou-se o grupo de todos os isolados quanto à sua susceptibilidade a um painel de leveduras killer previamente descritas, resultando em 75% sendo suscetíveis a pelo menos uma levedura killer, enquanto que as restantes não foram inibidas por qualquer cepa. C. albicans foi o grupo mais suscetível enquanto C. tropicalis teve o menor número de inibições. Não se obteve um padrão de inibição específico da espécie com este painel de leveduras killer. Metschnikowia pulcherrima, Pichia kluyveri e Wickerhamomyces anomalus foram as cepas que inibiram a maioria dos isolados de Candida spp.(AU)

Characterization of autochthonous wine yeasts isolated in vineyards of the State of Paraná, Brazil / Caracterização de leveduras vínicas autóctones isoladas em vinhedos do Estado do Paraná, Brasil

The transformation of grape must into wine is a complex microbiological process and is the product of the combined action of several genera and species of yeasts, dominated in the intermediate and final stages of fermentation by an alcohol-tolerant Saccharomyces sp. Current assay characterizes 42 autochthonous yeasts, isolated from the state of Paraná, southern Brazil, according to the following oenological properties: H2S production, fermentation rate, flocculation capacity, and killer phenotype (killer, sensitive and neutral characteristics). Current analysis is the first to evaluate killer phenotype in yeasts isolated from the State of Paraná, Brazil. With regard to their oenological traits, the yeasts evaluated were not suitable for winemaking and suggested that, depending on the harvest, the winemakers may face problems during the spontaneous wine production process.(AU)

A transformação do mosto de uva em vinho é um processo microbiológico complexo, resultado da ação combinada de diferentes gêneros e espécies de leveduras, no qual, entretanto, prevalece uma levedura, Saccharomyces sp. álcool-tolerante nos estágios intermediário e final da fermentação alcoólica. O objetivo deste trabalho foi caracterizar 42 leveduras autóctones isoladas da região sul do Brasil (Estado do Paraná) de acordo com as seguintes características enológicas: produção de H2S, taxa de fermentação, capacidade de floculação e fenótipo killer (características killer, sensível e neutra). Este estudo é o primeiro a avaliar fenótipo killer em leveduras isoladas do estado do Paraná. Com relação às características enológicas, as leveduras avaliadas não se mostraram promissoras para vinificação, sugerindo que, conforme a safra, o vinicultor pode enfrentar problemas durante o processo de fermentação espontânea das uvas para a elaboração de vinho.(AU)

ESTUDO DE BIOMARCADORES DE MERCÚRIO EM PEIXES DA AMAZÔNIA POR MEIO DA METALÔMICA E ANÁLISE DO ESTRESSE OXIDATIVO

O mercúrio é um metal tóxico, de distribuição ubíqua, com capacidade para bioacumulação e biomagnificação, que provoca alterações em biomoléculas importantes no metabolismo e contribui para o estabelecimento do estresse oxidativo em organismos aquáticos. Logo, o presente estudo teve por objetivo identificar e avaliar possíveis biomarcadores proteicos e/ou enzimáticos da toxicidade do mercúrio em peixes da região amazônica, por meio do estudo metaloproteômico e avaliação do estresse oxidativo. Foram utilizadas metodologias de fracionamento e identificação de proteínas por eletroforese bidimensional (2D PAGE) associada à espectrometria de massas (MS), mapeamento do mercúrio, em spots proteicos, por espectrometria de absorção atômica em forno de grafite (GFAAS) e avaliação de marcadores de estresse oxidativo. As espécies utilizadas foram o Plagioscion squamosissimus (corvina) e Colossoma macropomum (tambaqui), coletados na área da Usina Hidrelétrica de Jirau (rio Madeira-RO), que foram selecionadas em função da abundância populacional, interesse para a pesca e posição diferente na cadeia trófica (carnívoro e onívoro, respectivamente). Os tecidos amostrados foram o hepático, renal e muscular. Os resultados obtidos demonstraram maior concentração de mercúrio total no P. squamosissimus, espécie carnívora, e padrão de distribuição deste elemento igual para ambas as espécies(fígado>rim>músculo). Há tendência para maior atividade enzimática nos tecidos hepático e renal da espécie com maior concentração de mercúrio. Somente a atividade da glutationa peroxidase no rim e da glutationa-S-transferase no fígado do P.squamosissimus foi inferior, fato que pode ser explicado pela interação do mercúrio com essas enzimas, interferindo em sua conformação e função. Os dados obtidos por MS possibilitaram a identificação dos spots proteicos associados ao mercúrio, revelando proteínas envolvidas no metabolismo energético (gliceraldeído-3-fosfato, malato e Llactato desidrogenase, enolase, creatina quinase e fosfoglicerato mutase), transporte (hemoglobinas e , proteínas de ligação a ácidos graxos e GTPases), síntese e 3 degradação de proteínas (ubiquitina e ribossomal S27a e ribosomal 40S S24)diferenciação celular (nucleosídeo difosfato quinase), regulação gênica (pterina-4--carbinolamina desidratase e histona H4), defesa imunitária (fator de aprimoramento de células natural killer), metabolismo do cálcio (parvalbumina ), adipogênese (UPF0366), metabolismo de xenobióticos e esteroidogênese (citocromo P450scc) e sistema antioxidante (glutationa peroxidase, glutationa-S-transferase, superóxido dismutase, catalase e aldeído desidrogenase). Contribuindo assim para a compreensão dos mecanismos moleculares subjacentes à toxicidade ao mercúrio e fornecendo novas perspectivas sobre possíveis candidatos a biomarcadores de monitoramento ambiental.

Mercury is a toxic metal, of ubiquitous distribution, with capacity for bioaccumulation and biomagnification, that causes changes in important biomolecules in the metabolismo and contributes to the establishment of oxidative stress in aquatic organisms. Therefore, the present study aimed to identify and evaluate possible proteic and/or enzymatic biomarkers of the mercury toxicity in fish from the Amazon region, through a metalloproteomic study and evaluation of oxidative stress. Were used protein fractionation and identification me-thodologies by two-dimensional electrophoresis (2D PAGE) associated with mass spectrome-try (MS), mapping of mercury in protein spots by atomic absorption spectrometry in graphite furnace (GFAAS) and evaluation of oxidative stress markers. The species used were Plagios-cion squamosissimus (corvina) and Colossoma macropomum (tambaqui), collected in the area of the Jirau Hydroelectric Power Plant (Madeira-RO), which were selected due to the population abundance, interest for fishing and different position in the food chain (carnivo-rous and omnivorous, respectively). The tissues sampled were hepatic, renal and muscular. The results showed higher concentration of total mercury in P. squamosissimus, carnivorous species, and distribution pattern of this element equal to both species (liver> kid-ney>muscle). There is a tendency for greater enzymatic activity in the hepatic and renal tis-sues of the specie with the highest concentration of mercury. Only the activity of glutathione peroxidase in the kidney and glutathione-S-transferase in the liver of P.squamosissimus was lower, a fact that can be explained by the interaction of Mercury with these enzymes, inter-fering in their conformation and function. The data obtained by MS allowed the identification of the protein spots associated with mercury, revealing proteins involved in energy metabo-lism (glyceraldehyde-3-phosphate, malate and Llactate dehydrogenase, enolase, creatine kinase and phosphoglycerate mutase), transport ( and hemoglobins, fatty acid binding proteins and GTPases), synthesis and degradation of proteins (ubiquitin and ribosomal S27a and ribosomal 40S S24), cell differentiation (nucleoside diphosphate kinase), gene regulation (pterin-4--5 carbinolamine dehydratase and histone H4), immune defense (natural killer cell enhancement factor), calcium metabolism (-parvalbumin), adipogenesis (UPF0366), xeno-biotic metabolism and steroidogenesis (cytochrome P450scc) and antioxidante system (Glu-tathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase and al-dehyde dehydrogenase). Thus contributing to the understanding of the molecular mecha-nisms underlying mercury toxicity and providing new perspectives on potential candidates for environmental monitoring biomarkers.

Efeito dos hormônios tireoidianos no perfil angiôgenico e imune da decídua e glândula metrial de ratas e seu impacto na decidualização, vascularização e população de células uNKs na interface materno-fetal.

Durante a gestação, a decídua e a glândula metrial coordenam o processo de placentação permitindo a troca seletiva de nutrientes e metabólitos entre a mãe e o feto e dão subsídio para a permanência do embrião/feto semi-alogênico em íntimo contato com o útero. Mas, para o sucesso da gestação é fundamental que haja a interação coordenada entre a placenta e o útero comandanda por vários hormônios, dentre os quais os hormônios tireoidianos. Foram realizados dois experimentos distintos. O primeiro teve como objetivo avaliar a decidualização e a expressão de fatores angiogênicos na decídua e glândula metrial de ratas com hipotireoidismo e tratadas com L-tiroxina (T4) e o segundo objetivou avaliar o perfil de expressão espaçotemporal de fatores imunológicos e as células Natural Killer uterinas (uNKs) na decídua e glândula metrial de ratas com hipotireoidismo e tratadas com L-tiroxina (T4). Para o primeiro experimento foram utilizadas 72 ratas Wistar adultas distribuídas nos grupos hipotiroideo, tratado com T4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão do fator de crescimento endotelial vascular (VEGF), Flk-1 e Tie-2. Para o segundo experimento foram utilizadas 108 ratas Wistar adultas, distribuídas em três grupos experimentais, hipotireoideo, tratado com T4 e controle. As ratas foram eutanasiadas aos 7, 10, 12, 14 e 19 DG. Avaliou-se a detecção imunoistoquímica de IFN, MIF, IL15, iNOS e a marcação com Lectina DBA para evidenciação das células uNK DBA+ na decídua e glândula metrial. Além disso, avaliou-se a expressão gênica de Ifn, Il15 e iNos por RT-PCR em tempo real. Os dados de ambos os experimentos foram analisados pelo teste Student-Newman-Keuls (SNK). No primeiro experimento, evidenciou-se que o hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, nos animais hipotireoideos, mas ambos foram reduzidos aos 19 DG na glândula metrial, sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T4 apresentaram aumento do numero de vasos sanguíneos deciduais aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 aos 10 e 19 DG na decídua e na glândula metrial. O segundo experimento mostrou que a expressão de fatores pró e anti-inflamatórios estudados oscilou ao longo da gestação em todos os grupos tanto na decídua quanto na glândula metrial. O hipotireoidismo aumentou a expressão proteica de iNOS aos 7 DG, IL15 e MIF aos 10 e 12 dias, IFN e MIF aos 14 DG na decídua e/ou glândula metrial e dos transcritos gênicos para iNos aos 12 e 19 DG e para Ifn e Il5 aos 14 DG. Além disso, o hipotireoidismo reduziu a expressão proteica dos fatores pró-inflamatórios MIF, aos 7 DG, e IFN, aos 12 dias, e do transcrito gênico para Ifn aos 10 e 19 DG. O hipotireoidismo também reduziu a expressão proteica do fator anti-inflamatório iNOS aos 12, 14 e 19 DG e reduziu seus transcritos gênicos aos 10 e 14 DG. Os grupos tratados com T4 apresentaram aumento da expressão proteica de IFN, IL15 e MIF aos 7 DG, IL15, iNOS e MIF aos 10 DG, MIF aos 12 DG na glândula metrial, IFN e MIF na decídua basal aos 14 DG. Além disso, o tratamento com T4 reduziu a expressão proteica de IFN aos 12 e 19 DG, IL15 aos 12 e 14 DG e iNOS aos 12 e 14 DG. Aos 7 e 10 DG houve a redução da migração de células uNK DBA+ para a decídua em ambos os grupos de tratamento. Entretanto, aos 12 DG houve aumento no grupo tratado com T4 e aos 14 DG redução no grupo hipotireoideo. Pode-se concluir com o primeiro experimento, que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua associado ao aumento da expressão de Flk-1. Com o segundo experimento conclui-se que, tanto o hipotireoidismo quanto o tratamento com tiroxina alteram o perfil de expressão espaço22 temporal dos fatores imunológicos da decídua e da glândula metrial ao longo da gestação. A redução dos fatores pró-inflamatórios IFN e IL15 é mais predominante no grupo tratado com T4, enquanto o hipotireoidismo compromete o desenvolvimento de um ambiente antiinflamatório na interface materno-fetal, uma vez que a redução do fator anti-inflamatório iNOS e das células uNK DBA+ é principalmente evidenciada neste grupo

During gestation, the decidua and metrial gland coordinate the placentation process, allowing the selective exchange of nutrients and metabolites between mother and fetus, and provides subsidy for the semi-allogeneic embryo/fetus to remain in close contact with the uterus. But for the success of gestation, it is essential that there is a coordinated interaction between the placenta and the uterus by various hormones, among which thyroid hormones. Two different experiments were performed. The first one was goal to evaluate the decidualization and expression of angiogenic factors and the second one evaluates the spatiotemporal expression profile of immunological factors and the uterine Natural Killer cells (uNKs) in the decidua and metrial gland of rats with hypothyroidism and treated with L-tyroxine (T4). For the first experiment, 72 adults Wistar rats were distributed in the hypothyroid, T4 treated and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of vascular endothelial growth factor (VEGF), Flk-1 and Tie-2 expression. For the second experiment, 108 adults Wistar rats were distributed in three experimental groups, hypothyroid, treated with T4 and control. The rats were euthanized at 7, 10, 12, 14 and 19 DGs. The immunohistochemical detection of IFN, MIF, IL15, iNOS and the labeling with Lectin DBA were evaluated for the detection of uNK DBA+ cells in the decidua and metrial gland. In addition, the expression of Ifn, Il15 and iNos by real-time RT-PCR was evaluated. Data from both experiments were analyzed by the Student- Newman-Keuls (SNK) test. In the first experiment, it was shown that hypothyroidism reduced the decidua area at 10 and 19 DG. In addition, VEGF increased at 10 and 14 DG and Flk-1 only at 14 DGs in the hypothyroid animals, but both were reduced to 19 DGs in the metrial gland, without significantly altering the area occupied by the blood vessels. The rats treated with T4 showed an increase in the number of deciduous blood vessels at 10 and 19 DG. In addition, at 10 DGs, excess T4 resulted in the increase of Flk-1 in the decidua and in the metrial gland. Hypothyroidism increased Tie-2 at 10 and 19 DGs in the decidua and metrial gland. The second experiment showed that the expression of pro and anti-inflammatory factors studied oscillated throughout gestation in all groups, both in the decidua and in the metrial gland. Hypothyroidism increased the protein expression of iNOS at 7 DGs, IL15 and MIF at 10 and 12 days, IFN and MIF at 14 DGs in the decidua and/or metrial gland and the gene transcripts for iNos at 12 and 19 DGs and for Ifn and Il5 To 14 DGs. In addition, hypothyroidism reduced the protein expression of the proinflammatory factors MIF, at 7 DG, and IFN at 12 days, and of the gene transcript for Ifn at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of the anti-inflammatory factor iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. The T4 treated groups showed increased expression of IFN, IL15 and MIF at 7 DG, IL15, iNOS and MIF at 10 DG, MIF at 12 DGs in the metrial gland, IFN and MIF at the baseline decidua at 14 DGs. In addition, treatment with T4 reduced the protein expression of IFN at 12 and 19 DG, IL15 at 12 and 14 DG and iNOS at 12 and 14 DGs. At 7 and 10 DG there was a reduction of migration of uNK DBA+ cells to decidua in both treatment groups. However, at 12 DG there was an increase in the group treated with T4 and at 14 DG a reduction in the hypothyroid group. It can be concluded from the first experiment that hypothyroidism reduces the decidua area and increases the expression of VEGF, Tie-2 and Flk-1. Excess T4 promotes tissue angiogenesis by increasing the number of vessels in the decidua associated with increased expression of Flk-1. With the second experiment it was concluded that both hypothyroidism and thyroxine treatment altered the spatiotemporal expression profile of the immunological factors of the decidua and metrial gland throughout pregnancy. The reduction of the proinflammatory factors IFN and IL15 is more predominant in the group treated with T4, whereas hypothyroidism compromises the development of an anti-inflammatory environment at 24 the feto-maternal interface, since the reduction of the anti-inflammatory factor iNOS and of the uNK DBA+ cells is mainly evidenced in this group.

Levels of interleukins 12 (IL-12) and 13 (IL-13), hepatitis B and C serology, and blood cultures among acute myeloid leukemia (AML) patients in Egypt

There is an interest in the use of IL-12 as a possible anti-cancer drug to induce immune responses and anti-IL-13 formulations to treat the undesirable effects of IL-13. Thus, the present study aimed at analyzing IL-12 and IL-13 profiles, viral hepatitis serology and blood cultures in acute myeloid leukemia (AML) patients. Forty individuals (20 without septicemia - Group A, and 20 with septicemia - Group B) and 20 healthy controls were evaluated. Hepatitis B virus antigens (HBsAg) and hepatitis C virus antibodies (HCV Ab) were quantified using commercial ELISA kits. IL-12 and IL-13 levels were estimated in culture supernatant of mitogen-stimulated peripheral blood mononuclear cells by ELISA. Significantly low IL-12 values were observed among AML patients compared to controls whereas the opposite was observed regarding IL-13. IL-12 levels were found to be elevated in the follow-up cases. M4 and M5 subtypes of AML presented higher IL-12 levels than M1 and M2 subtypes. The isolated organisms from AML with septicemia were Staphylococcus aureus (35 percent), Esherichia coli (25 percent), coagulase-negative staphylococci (25 percent), and Candida (15 percent). Fungemia cases showed higher IL-12 values than bacteremia cases. In conclusion, IL-12 and IL-13 should be further tested in large-scale studies to provide future immunotherapy against AML.(AU)

Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A) patients

Hepatitis C virus (HCV) patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL) 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I) and 15 patients with chronic HCV infection and normal platelet count as controls (Group II). All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR), abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001) while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001) in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I), r = 0.038, p = 0.89 (Group II)] or IL-12 [r = 0.497, p = 0.06 (Group I), r = 0.499, p = 0.058 (Group II)]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033) or IL-12 (r = 0.967, p = 0.001), while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = -0.08 and p = 0.851 for IL-12). Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.(AU)

Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A) patients

Hepatitis C virus (HCV) patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL) 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I) and 15 patients with chronic HCV infection and normal platelet count as controls (Group II). All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR), abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001) while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001) in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I), r = 0.038, p = 0.89 (Group II)] or IL-12 [r = 0.497, p = 0.06 (Group I), r = 0.499, p = 0.058 (Group II)]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033) or IL-12 (r = 0.967, p = 0.001), while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = –0.08 and p = 0.851 for IL-12). Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.(AU)

Biocontrol by yeasts: perspectives in aplication for fruits safety / Biocontrole de doenças pós-colheita de frutas por leveduras: perspectivas de aplicação e segurança alimentar

The agrifood system of fruits is a relevant area in Brazil, where the efforts are focused on competitiveness of both tropical and subtropical ones. Considerable losses in the economically important fruits are elapsed by susceptibility to field fungal infection, followed by further storage fungi attack. Prominent interest concern on biocontrol as an alternative for traditional chemical treatment in pos-harvesting disease control, due the low possibility of undesirable residues. The perspective is targeted on yeasts, whose wide safety is already demonstrated by food fermentative processes. The applicability of yeast killer factor is unknown, but the potentially innocuous compounds point as a promising bioactive product for use in biodegradable biofilms. Revised are the possible application of beneficial interaction of yeasts in the control of deteriorative/mycotoxigenic fungi, aiming additional contribution for fresh fruit safety in the globalized world, where the current Brazilian economy are in progressive advance.

O sistema agroalimentar de frutas é uma área relevante, onde o Brasil vem concentrando esforços para garantir a competitividade de frutas. Perdas consideráveis na produção de frutas economicamente importantes decorrem da susceptibilidade à infecção fúngica no campo, assim como posterior ataque na armazenagem. Entre as alternativas ao tradicional tratamento químico de doenças pós-colheita de frutos, destaque especial enfoca-se sobre biocontrole, em função da baixa possibilidade de resíduos tóxicos. No contexto, abre-se perspectiva para as leveduras, com ampla inocuidade demonstrada nos processos fermentavivos. Desconhece-se a aplicabilidade de fator killer presente em leveduras, mas a potencialidade de fatores inócuos à saúde dos consumidores aponta as leveduras como compostos bioativos promissores na aplicação em biofilmes biodegradáveis. A revisão discorre sobre interação benéfica de leveduras no controle de fungos deteriorantes/micotoxigênicos, visando contribuição adicional à segurança de frutas frescas no mundo globalizado, onde a economia brasileira mantém um avanço progressivo.

Biocontrol by yeasts: perspectives in aplication for fruits safety / Biocontrole de doenças pós-colheita de frutas por leveduras: perspectivas de aplicação e segurança alimentar

The agrifood system of fruits is a relevant area in Brazil, where the efforts are focused on competitiveness of both tropical and subtropical ones. Considerable losses in the economically important fruits are elapsed by susceptibility to field fungal infection, followed by further storage fungi attack. Prominent interest concern on biocontrol as an alternative for traditional chemical treatment in pos-harvesting disease control, due the low possibility of undesirable residues. The perspective is targeted on yeasts, whose wide safety is already demonstrated by food fermentative processes. The applicability of yeast killer factor is unknown, but the potentially innocuous compounds point as a promising bioactive product for use in biodegradable biofilms. Revised are the possible application of beneficial interaction of yeasts in the control of deteriorative/mycotoxigenic fungi, aiming additional contribution for fresh fruit safety in the globalized world, where the current Brazilian economy are in progressive advance.

O sistema agroalimentar de frutas é uma área relevante, onde o Brasil vem concentrando esforços para garantir a competitividade de frutas. Perdas consideráveis na produção de frutas economicamente importantes decorrem da susceptibilidade à infecção fúngica no campo, assim como posterior ataque na armazenagem. Entre as alternativas ao tradicional tratamento químico de doenças pós-colheita de frutos, destaque especial enfoca-se sobre biocontrole, em função da baixa possibilidade de resíduos tóxicos. No contexto, abre-se perspectiva para as leveduras, com ampla inocuidade demonstrada nos processos fermentavivos. Desconhece-se a aplicabilidade de fator “killer” presente em leveduras, mas a potencialidade de fatores inócuos à saúde dos consumidores aponta as leveduras como compostos bioativos promissores na aplicação em biofilmes biodegradáveis. A revisão discorre sobre interação benéfica de leveduras no controle de fungos deteriorantes/micotoxigênicos, visando contribuição adicional à segurança de frutas frescas no mundo globalizado, onde a economia brasileira mantém um avanço progressivo.