Interaction of Mycoplasma genitalium with host cells: evidence for nuclear localization

Mycoplasma genitalium (Mg) is a mollicute that causes a range of human urogenital infections. A hallmark of these bacteria is their ability to establish chronic infections that can persist despite completion of appropriate antibiotic therapies and intact and functional immune systems. Intimate adherence and surface colonization of mycoplasmas to host cells are important pathogenic features. However, their facultative intracellular nature is poorly understood, partly due to difficulties in developing and standardizing cellular interaction model systems. Here, we characterize growth and invasion properties of two Mg strains (G37 and 1019V). Mg G37 is a high-passage laboratory strain, while Mg 1019V is a low-passage isolate recovered from the cervix. The two strains diverge partially in gene sequences for adherence-related proteins and exhibit subtle variations in their axenic growth. However, with both strains and consistent with our previous studies, a subset of adherent Mg organisms invade host cells and exhibit perinuclear targeting. Remarkably, intranuclear localization of Mg proteins is observed, which occurred as early as 30 min after infection. Mg strains deficient in adherence were markedly reduced in their ability to invade and associate with perinuclear and nuclear sites.

Functional interferences in host inflammatory immune response by airway allergic inflammation restrain experimental periodontitis development in mice

Aims Periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. Material and Methods Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. Results PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, -gamma, IL-17A, receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor gamma and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. Conclusion Our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.

Transcriptome and gene expression profile of ovarian follicle tissue of the triatomine bug Rhodnius prolixus

Insect oocytes grow in close association with the ovarian follicular epithelium (OFE), which escorts the oocyte during oogenesis and is responsible for synthesis and secretion of the eggshell. We describe a transcriptome of OFE of the triatomine bug Rhodnius prolixus, a vector of Chagas disease, to increase our knowledge of the role of FE in egg development. Random clones were sequenced from a cDNA library of different stages of follicle development. The transcriptome showed high commitment to transcription, protein synthesis, and secretion. The most abundant cDNA was a secreted (S) small, proline-rich protein with maximal expression in the vitellogenic follicle, suggesting a role in oocyte maturation. We also found Rp45, a chorion protein already described, and a putative chitin-associated cuticle protein that was an eggshell component candidate. Six transcripts coding for proteins related to the unfolded-protein response (UPR) by were chosen and their expression analyzed. Surprisingly, transcripts related to UPR showed higher expression during early stages of development and downregulation during late stages, when transcripts coding for S proteins participating in chorion formation were highly expressed. Several transcripts with potential roles in oogenesis and embryo development are also discussed. We propose that intense protein synthesis at the FE results in reticulum stress (RS) and that lowering expression of a set of genes related to cell survival should lead to degeneration of follicular cells at oocyte maturation. This paradoxical suppression of UPR suggests that ovarian follicles may represent an interesting model for studying control of RS and cell survival in professional S cell types. (C) 2011 Elsevier Ltd. All rights reserved.

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25 - 40% of the similar to 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non- human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Leptin and the Immune Response An Active Player or an Innocent Bystander?

Leptin is involved in the control of energy storage by the body. Low serum leptin levels, as seen in starvation, are associated with impaired inflammatory T cell responses that can be reversed by exogenous leptin. Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Several defects in T cell function have also been described, and allergy, autoimmune disease, and lymphomas or other malignancies can be present. Previous studies in Brazilian CVID patients have shown that, in contrast with mononuclear cells from healthy controls, CVID cells cultured with phytohemagglutinin and added leptin increased the proliferative response and decreased activation-induced apoptosis. Interleukin (IL)-2 and especially IL-4 production also increased significantly, although the effects of exposure to leptin were not observed uniformly in CVID patients. The majority, however, responded in some degree, and some exhibited completely restored values of the four parameters. These remarkable results indicate leptin could be used to improve immune function in these patients. On the other hand, we found no specific correlation between serum leptin levels and the number of infectious events over a 24-month period, presence of autoimmunity, allergies, or cancer in these patients. The results suggest that the absolute value of serum leptin does not determine the clinical behavior of patients or responses to leptin in vitro. Of note is the divergence between serum leptin, response to leptin in vitro, and the presence of autoimmunity, indicating the need to identify the cellular and molecular players involved in the regulation of the immune response by leptin in CVID.

Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has been shown to down-regulate experimental allergic asthma, a finding that reinforced the hygiene hypothesis. We have previously found that recombinant BCG (rBCG) strain that express the genetically detoxified Si subunit of pertussis toxin (rBCG-S1PT) exerts an adjuvant effect that enhances Th1 responses against BCG proteins. Here we investigated the effect of this rBCG-S1PT on the classical ovalbumin-induced mouse model of allergic lung disease. We found that rBCG-S1PT was more effective than wild-type BCG in preventing Th2-mediated allergic immune responses. The inhibition of allergic lung disease was not associated with increased concentration of suppressive cytokines or with an increased number of pulmonary regulatory T cells but was positively correlated with the increase in IFN-gamma-producing T cells and T-bet expression in the lung. In addition, an IL-12-dependent mechanism appeared to be important to the inhibition of lung allergic disease. The inhibition of allergic inflammation was found to be restricted to the lung because when allergen challenge was given by the intraperitoneal route, rBCG-S1PT administration failed to inhibit peritoneal allergic inflammation and type 2 cytokine production. Our work offers a nonclassical interpretation for the hygiene hypothesis indicating that attenuation of lung allergy by rBCG could be due to the enhancement of local lung Th1 immunity induced by rBCG-S1PT. Moreover, it highlights the possible use of rBCG strains as multipurpose immunomodulators by inducing specific immunity against microbial products while protecting against allergic asthma.

Interactions of mast cell degranulating peptides with model membranes: A comparative biophysical study

In the last decade, there has been renewed interest in biologically active peptides in fields like allergy, autoimmume diseases and antibiotic therapy. Mast cell degranulating peptides mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, in a fast and concentration-dependent way. The mechanism of action of peptide HR1 on model membranes was investigated comparatively to other mast cell degranulating peptides (Mastoparan, Eumenitin and Anoplin) to evidence the features that modulate their selectivity. Using vesicle leakage, single-channel recordings and zeta-potential measurements, we demonstrated that HR1 preferentially binds to anionic bilayers, accumulates, folds, and at very low concentrations, is able to insert and create membrane spanning ion-selective pores. We discuss the ion selectivity character of the pores based on the neutralization or screening of the peptides charges by the bilayer head group charges or dipoles. (C) 2009 Elsevier Inc. All rights reserved.

Kunskapens betydelse vid födoämnesallergi och anafylaxi : en systematisk litteraturstudie

Syftet med föreliggande litteraturstudie var att beskriva kunskapens betydelse för personer med födoämnesallergi, samt när det gäller förebyggande av anafylaxi. Den metod som användes var en systematisk litteraturstudie, där totalt tretton kvantitativa och två kvalitativa artiklar användes i resultatet. De databaser som användes var Pubmed, Elin@dalarna och CINAHL. Resultatet visade att beträffande kunskapens betydelse var majoriteten av de medicinska frågorna i en studie som besvarades via Internet frågor som berörde födoämnesallergi och allergiska reaktioner. Över hälften av ungdomarna uppgav att deras livskvalitet och hälsa påverkades och ovissheten och okunskapen om allergin påverkade deras livskvalitet negativt. Det visade sig även att endast en fjärdedel av läkarna gav detaljerad undervisning och information om hur viktigt det var med undvikande av allergen vid födoämnesallergi. Beträffande kunskapens betydelse vid förebyggande av anafylaxi visade flera studier att anafylaxi var vanligt förekommande hos vuxna och ungdomar med födoämnesallergi. Ungdomar hade otillräcklig kunskap om anafylaxi och hälften av ungdomarna uppgav att de ätit de födoämnen de var allergiska emot. Anvisningar och information om akuta födoämnesreaktioner var låg hos vuxna och tonåringar upplevde ett stort behov av undervisning, då de tog mer risker än vuxna.

Tillmatning av nyfödda barn på BB i Sverige : följs föreskrifter och rekommendationer

Syftet var att beskriva omvårdnaden kring nyfödda barns tillmatning på svenska BB-avdelningar, om föreskrifter följdes och om hänsyn togs till eventuell allergihereditet. Metod: Deskriptiv tvärsnittsstudie med kvantitativ ansats Resultat: Av alla nyfödda barn vid 26 barnkliniker i Sverige vecka 26 år 2009 (n=849) tillmatades 18 % . Moderns bröstmjölk gavs till 16% medan 78 % tillmatades med komjölksbaserad modersmjölksersättning. Den vanligaste orsaken till tillmatning av ersättning var att mammans egen mjölkproduktion inte hade kommit igång (24 %). Andra vanligt förekommande anledningar till tillmatning var lågt blodsocker (18 %) samt sugproblem hos barnen (16 %). Sexton barn tillmatades trots ett blodsockervärde motsvarande >2.2mmol/l. Vad gäller allergiförekomst tillfrågades endast 37 % av barnens föräldrar före tillmatning. Dokumentation om tillmatning fanns noterat i 80 % av barnens journaler. Motsvarande siffra för mammornas journaler var 34 %. Konklusion: Bristfälliga omvårdnadsåtgärder vidtas i samband med tillmatning av nyfödda spädbarn på BB-avdelningar, där allergifrågor ställs i för låg utsträckning. BB-kliniker har varierande referensvärde för vad som räknas som lågt blodsocker. Omvårdnadsbehov för nyfödda barn och deras föräldrar, där förmedlad kunskap om amningens betydelse, tas inte på allvar och oklara riktlinjer skapar förvirring. Föreskrifter och riktlinjer bör följas i större utsträckning an vad denna studie visar.

Integridade tissular de pacientes com úlceras venosas: um estudo baseado na Classificação dos Resultados de Enfermagem

The venous ulcer is an epidemiological problem of high prevalence, causing disability and dependence. Assess the tissue impairment level of patients with venous lesions, within a nursing referential, is relevant for the implementation of a directed assistance to specific clientele. Thus, this work aims to characterize the health status regarding the integrity the lower limbs skin of patients with venous ulcers, according to the of tissue integrity outcome indicators from the Nursing Outcomes Classification. A cross-sectional study conducted in a university hospital in Natal - Rio Grande do Norte. The sample consisted of 50 participants, selected through consecutive sampling. Data collection occurred through a interview and physical examination form and a operational definitions tool for indicators of the nursing Tissue Integrity outcome directed to patients with venous ulcer, applied from February to June 2012. Data analysis was done by descriptive statistics and nonparametric tests (Spearman, Kruskal-Wallis and Mann-Whitney tests). The project was approved by the Research Ethics Committee with protocol 608/11 and Presentation Certificate to Ethical Consideration No. 0038.0.294.000-11. The results were presented using three scientific articles derivatives of research. It was found that the indicators show moderate impairment, light and not impaired, as the median. The respondents had an average of 59.72 years, 66% female, 50% were retired, 60% with a partner, 44% had arterial hypertension, 26% allergies, 20% diabetes mellitus, 96% were sedentary, 14% drank alcohol and 6% were smokers. There was a statistically significant correlation of low intensity between age and hydration (p=0.032; rs=-0.304) and skin desquamation (p=0.026; rs=-0.316), family income and necrosis (p=0.012; rs=-0.353); Ankle Brachial Index and tissue perfusion (p=0,044; rs=-0,329); Diabetes Mellitus and texture (p=0.015) and tissue perfusion (p=0.026); allergy and texture (p=0.034), physical activity and hydration (p=0.034), smoking and thickness (p=0.018), and alcohol consumption and exudate (p=0.045). We conclude that the patients had light to moderate impairment, indicating a good state of health on the integrity of the skin of the lower limbs, according to the indicators of the outcome of tissue integrity Classification Nursing Outcomes valued in the present study. It is believed that the evaluation of impairment tissue using a self-nursing system and its relation with socioeconomic, clinical and risk factors are unique tools in the care planning and in the wound healing

Latex use as an occlusive membrane for guided bone regeneration

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação do atendimento anestésico da criança e do adolescente em um hospital universitário

JUSTIFICATIVA E OBJETIVOS: Qualidade em anestesia e na satisfação dos pacientes têm tido acentuado destaque. O objetivo foi avaliar o atendimento anestésico de crianças e adolescentes, entrevistando seus responsáveis. MÉTODO: Foram entrevistados 230 responsáveis por crianças e adolescentes submetidos à anestesia no período compreendido entre abril e dezembro de 2003. Realizou-se entrevista na visita pós-operatória através de questionário com quatro itens: identificação das crianças e de adolescentes e seus responsáveis (item 1); esclarecimentos na visita pré-anestésica (item 2), quanto à anestesia (item 3) e à recuperação pós-anestésica (SRPA) (item 4), determinando-se quem dera as informações aos entrevistados e se houvera complicação no pós-anestésico. O responsável atribuiu nota de 0 a 10 ao Serviço de Anestesiologia. RESULTADOS: A pesquisa foi respondida pela mãe em 189 (82,2%) casos. A maioria dos entrevistados, 114 (75,6%), tinha entre 20 e 39 anos, era casada (148 a 64,3%) e 140 (60,9%) não tinham ocupação. Para 89%, o anestesiologista se identificou; para 37% e 77,4%, esclareceu sobre importância e tempo do jejum; 82%, sobre anemia; 90%, alergia; 46,8%, importância da SRPA; 42,2%, tempo de permanência; 72,9%, estado de saúde de sua criança. Não houve apreensões para 49%, 58% e 58%, respectivamente, no pré, intra e pós-anestésico. Gostariam de ter estado com sua criança/adolescente na chegada à SRPA 78,9%. Foram relacionadas preocupações no período pré, intra e pós-anestésico com o sexo e a idade do paciente - não ter tido nenhuma preocupação - maioria dos entrevistados - e com a escolaridade do entrevistado - quanto mais completa, menor foi o número e a variedade das preocupações relatadas. As notas atribuídas ao Serviço de Anestesiologia tiveram maior freqüência entre 7 e 10 (97,4%). CONCLUSÕES: Considera-se que o Serviço de Anestesiologia desenvolve bom trabalho, apesar de falhas na comunicação, que são de solução simples e dependem mais da vontade do serviço que de seu conhecimento científico.

Autoimmune thyroid disease as a risk factor for angioedema in patients with chronic idiopathic urticaria: a case-control study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Imunologia da paracoccidioidomicose

Paracoccidioidomicose é a mais prevalente micose sistêmica na América Latina, em pacientes imunocompetentes, sendo causada pelo fungo dimórfico Paracoccidioiddes brasiliensis. O estudo da sua imunopatogênese é importante na compreensão de aspectos relacionados à história natural, como a imunidade protetora, e à relação entre hospedeiro e parasita, favorecendo o entendimento clínico e a elaboração de estratégias terapêuticas. O polimorfismo clínico da doença depende, em última análise, do perfil de resposta imune que prevalece expresso pelo padrão de citocinas teciduais e circulantes, além da qualidade da resposta imune desencadeada, que levam ao dano tecidual