Lack of circulating toxoplasma gondii DNA in seropositive patients with bipolar or schizophrenia spectrum disorders.

Toxoplasmosis has been previously associated with an increased risk of having Schizophrenia or Bipolar disorder in several epidemiological studies. The aim of this observational, cross-sectional study was to examine the seroprevalence of Toxoplasma infection in a cohort of Italian psychiatric inpatients and to verify the presence of circulating Toxoplasma gondii DNA in the seropositive subjects. Sixty-three patients affected by bipolar or schizoaffective disorders according to DSM-5 criteria were enrolled. The presence of Toxoplasma infection was firstly examined using an indirect serological method (ELFA), and three different direct PCR-based methods were performed to detect circulating DNA in the seropositive patients. The seroprevalence of infection was 28.6%, with a significant association between higher age and the infection status. PCR, nested-PCR and Real-Time PCR revealed no positive samples for Toxoplasma gondii. This result is in contrast with recent data from case-control studies that detected parasite genome in patients with different neuropsychiatric diagnosis without clinical evidence of acute toxoplasmosis. Our findings are to be interpreted with caution, because of the small sample size, the heterogeneity of enrolled patients and the observational nature of the study. Further studies are needed to better define the clinical features correlated to the seropositive status in neuropsychiatric patients.

Exopolysaccharide from Bifidobacterium longum subsp. longum 35624™ modulates murine allergic airway responses.

Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B. longum 35624 cultures was used for in vitro, ex vivo and in vivo studies. Human monocyte-derived dendritic cells (MDDCs) were used to investigate in vitro immunological responses to EPS. Cytokine secretion, expression of surface markers and signalling pathways were examined. The ovalbumin (OVA) respiratory allergy murine model was used to evaluate the in vivo immunomodulatory potential of EPS. In addition, interleukin (IL)-10 knockout (KO) mice and anti-Toll-like receptor (TLR)-2 blocking antibody were used to examine the underlying protective mechanisms of intranasal EPS administration. Stimulation of human MDDCs with EPS resulted in IL-10 secretion, but not proinflammatory cytokines. IL-10 secretion was TLR-2-dependent. Eosinophil recruitment to the lungs was significantly decreased by EPS intranasal exposure, which was associated with decreased expression of the Th2-associated markers C-C motif chemokine 11 (CCL11), C-C chemokine receptor type 3 (CCR3), IL-4 and IL-13. TLR-2-mediated IL-10 secretion was shown to be required for the reduction in eosinophils and Th2 cytokines. EPS-treatment reduced eosinophil recruitment within the lung in a respiratory inflammation mouse model, which is both TLR-2 and IL-10 mediated. EPS can be considered as a novel molecule potentially reducing the severity of chronic eosinophil-related airway disorders.

Histamine receptor 2 modifies iNKT cell activity within the inflamed lung.

BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. RESULTS: The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. CONCLUSIONS: This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.

Optofluidic holographic microscopy with custom field of view (FoV) using a linear array detector.

Simple and effective imaging strategies are of utmost interest for applications on a lab-on-chip scale. In fact, the majority of diagnostic tools for medical as well as biotechnological studies still employ image-based approaches. Having onboard the chip a compact but powerful imaging apparatus with multiple imaging capabilities, such as 3D dynamic focusing along the optical axis, unlimited field of view (FoV) and double outputs, namely, intensity and quantitative phase-contrast maps of biological objects, is of extreme importance for the next generation of Lab-on-a-Chip (LoC) devices. Here we present a coherent 3D microscopy approach with a holographic modality that is specifically suitable for studying biological samples while they simply flow along microfluidic paths. The LoC device is equipped with a compact linear array detector to capture and generate a new conceptual type of a digital hologram in the space-time domain, named here as Space-Time Digital Hologram (STDH). The reported results show that the method is a promising diagnostic tool for optofluidic investigations of biological specimens.

The major allergen of the Parietaria pollen contains an LPS-binding region with immuno-modulatory activity.

BACKGROUND: The major allergens in Parietaria pollen, Par j 1 and Par j 2, have been identified as lipid transfer proteins. The family of the Par j 1 allergens is composed of two isoforms, which differ by the presence of a 37 amino acid peptide (Par37) exclusive to the Par j 1.0101 isoform. The goal of this study was to elucidate the biological properties of the Par37 peptide. METHODS: In silico analysis, spectrofluorimetric experiments and in vitro cell culture assays were used to identify the biological properties of Par37. In addition, a mouse model of sensitization was used to study the influence of Par37 in the murine immune response. RESULTS: In silico analysis predicted that Par37 displays characteristics of a host defence peptide. Spectrofluorimetric analysis, real-time PCR and ELISA assays demonstrated that Par37 possesses an LPS-binding activity influencing cell signalling in vitro. In RAW264.7 cells, LPS-induced IL-6 and TNF-α transcription and translation were inhibited after preincubation with Par37. Consistent with these data, inhibition of IFN-γ secretion was observed in murine spleen cells and in human PBMC. Finally, mice immunized with the two Par j 1 isoforms differing in the presence or absence of the Par37 peptide showed different immunological behaviours in vivo. CONCLUSIONS: This study demonstrates that the Par j 1.0101 allergen displays LPS-binding activity due to the presence of a 37 amino acid COOH-terminal region and that this region is capable of influencing cytokine and antibody responses in vitro and in vivo.

Cognitive, psychological and psychiatric effects of ionizing radiation exposure.

Radiation exposure leads to an increased risk for cancer and, possibly, additional ill-defined non-cancer risk, including atherosclerotic, cardiovascular, cerebro-vascular and neurodegenerative effects. Studies of brain irradiation in animals and humans provide evidence of apoptosis, neuro-inflammation, loss of oligo-dendrocytes precursors and myelin sheaths, and irreversible damage to the neural stem compartment with long-term impairment of adult neurogenesis. With the present paper we aim to present a comprehensive review on brain effects of radiation exposure, with a special focus on its impact on cognitive processes and psychological functions, as well as on their possible role in the pathophysiology of different psychiatric disorders.

Oral therapeutic administration of a probiotic mixture suppresses established Th2 responses and systemic anaphylaxis in a murine model of food allergy.

BACKGROUND: No effective treatment is available for food allergy and its primary management still consists of avoiding relevant allergens. Probiotics are claimed to beneficially affect the immune system. We sought to investigate the therapeutic potential of VSL#3 probiotic mixture on specific immune responses and anaphylactic reaction induced in mice by the major food allergen shrimp tropomyosin (ST). METHODS: The cytokine production by spleen cell from ST-sensitized mice upon allergen re-stimulation in the presence of VSL#3 was analysed. Next, the effects of oral administration of VSL#3 on allergen-induced anaphylaxis and Th2 response in the murine model of food allergy to ST was investigated by evaluating symptom score and histamine content in the faeces after allergen challenge, antibody response in serum and faeces, and cytokine and transcription factor expression in the jejunum. RESULTS: The in vitro studies on mouse spleen cells indicates that the VSL#3 preparation has the capacity to shift a polarized Th2 response to a Th1/T regulatory-type profile. Oral therapeutic administration of VSL#3 to ST-sensitized mice significantly reduces symptom score and histamine release in the faeces following allergen challenge, as well as specific IgE response. In the jejunum, IL-4, IL-5 and IL-13 tissue content was significantly reduced, whereas FOXP3 and IL-27 mRNA expression, IL-10, TGF-ß and IFN-γ tissue content were up-regulated. CONCLUSIONS: Oral therapeutic treatment with the probiotic mixture VSL#3 is effective in redirecting allergen-specific Th2-polarized immune responses towards Th1-T regulatory responses and in the protection against anaphylactic reactions induced by the allergen in a murine model of food allergy.

Congenital and acquired pathology of ovary and tubular genital organs in ewes: a review.

Advances in our understanding of ovarian cyclicity, pathogenesis of subfertility and/or infertility and reproductive pathology in food animals have frequently entailed examination of abattoir material. Despite the fact that most lesions in ewes are likely to be of relatively minor significance to fertility, results of previous studies suggest that lesions of the female reproductive system may represent a significant source of loss to sheep husbandry. The objective of this paper is to review the pathophysiology, the effects on reproductive efficiency and the key gross and histological diagnostic features of congenital and acquired pathology of ovary and tubular genital organs in ewes.

[Community-acquired pneumonia in adults. Clinical practice guideline for Argentina. Study Group on Community Acquired Pneumonia]. / Neumonía adquirida en la comunidad (NAC) en adultos. Guía de práctica clínica para la Argentina. Grupo de Estudio de las NAC.

Community-acquired pneumonia (CAP) affects approximately 1% of the population annually. Initial antimicrobial therapy is most often empirical. Guidelines designed in other countries for the empirical management of CAP are not recommended for use in Argentina. Studies from other countries were considered together with unpublished local data to define the potential etiologic microorganisms and their antimicrobial susceptibility. Recommended diagnostic tests, groups of patients for different therapies and hospitalization criteria were defined. Severe CAP requiring intensive care was distinguished from the rest because of its distinct spectrum of etiologic agents and its high mortality, requiring a more focused therapy. Age, coexisting conditions and severity of illness were taken into account in the election of therapy.

Evaluación clínica y funcional del aparato respiratorio en el Sindrome de Sj÷gren primario por métodos no invasivos. / Clinical and functional non invasive evaluation or respiratory system in Primary Sj÷grens Syndrome.

Se estudiaron en forma no invasiva 11 pacientes con Sindrome de Sj÷gren primario según los criterios de Fox y col.para determinar la presencia de alteraciones clínicas y funcionales del aparato respiratorio.Se les efectuó historia clínica y teleradiografía de tórax.La evaluación funcional respiratoria incluyó :espirometría y curva flujo-volúmen ,difusión de monóxido de carbono,volúmens pulmonares,resistencia y conductancia de la vía aérea en pletismógrafo corporal y medición de presiones respiratorias máximas.Los pacientes fueron todas mujeres con una edad media de 52,8 + 10,3 años.5 pacientes refirieron disnea de esfuerzo y 3 pacientes tos crónica ,una de ellas con bronquitis a repetición y expectoración diaria.2 pacientes mostraron cambios en la espirometría compatibles con obstrucción leve de la vía aérea (1 con relación VEF1/CVF baja y las 2 con FMF25-75 bajos) .Los volúmenes pulmonares y la difusión no mostraron alteraciones significativas .4 pacientes tenían una conductancia específica francamente reducida.En 6 pacientes se encontró reducción de las presiones respiratorias máximas (3 tenían presión inspiratoria máxima reducida y las 6 presión espiratoria máxima baja).Los 6 pacientes tenían enzimas musculares normales.Se discute el posible significado de los hallazgos pletismográficos y la reducción de las presiones respiratorias máximas,hallazgos ambos no descriptos hasta la fecha en el Sindrome de Sj÷gren primario.

Evaluación clínica y funcional del aparato respiratorio en el Sindrome de Sjögren primario por métodos no invasivos. / Clinical and functional non invasive evaluation or respiratory system in Primary Sjögren's Syndrome.

Se estudiaron en forma no invasiva 11 pacientes con Sindrome de Sjögren primario según los criterios de Fox y col.para determinar la presencia de alteraciones clínicas y funcionales del aparato respiratorio.Se les efectuó historia clínica y teleradiografía de tórax.La evaluación funcional respiratoria incluyó :espirometría y curva flujo-volúmen ,difusión de monóxido de carbono,volúmens pulmonares,resistencia y conductancia de la vía aérea en pletismógrafo corporal y medición de presiones respiratorias máximas.Los pacientes fueron todas mujeres con una edad media de 52,8 + 10,3 años.5 pacientes refirieron disnea de esfuerzo y 3 pacientes tos crónica ,una de ellas con bronquitis a repetición y expectoración diaria.2 pacientes mostraron cambios en la espirometría compatibles con obstrucción leve de la vía aérea (1 con relación VEF1/CVF baja y las 2 con FMF25-75 bajos) .Los volúmenes pulmonares y la difusión no mostraron alteraciones significativas .4 pacientes tenían una conductancia específica francamente reducida.En 6 pacientes se encontró reducción de las presiones respiratorias máximas (3 tenían presión inspiratoria máxima reducida y las 6 presión espiratoria máxima baja).Los 6 pacientes tenían enzimas musculares normales.Se discute el posible significado de los hallazgos pletismográficos y la reducción de las presiones respiratorias máximas,hallazgos ambos no descriptos hasta la fecha en el Sindrome de Sjögren primario.

Multipurpose analyzers for photoelectron statistics: implementation and use.

The statistical properties of variously scattered laser light can be derived from photocount data through the estimate of different functions. Even if the second-order correlation usually plays the main role, other function (e.g., triggered and nontriggered distributions, moments of various order, and higher-order correlations) may give more appropriate results in many experimental conditions. We present a multifunction analyzer whose working principle is based on the acquisition of a long sequence of interpulse intervals (through a circuitally simple personal-computer front-end interface), which is followed by the off-line calculation of one or more of the functions for which an algorithm is available. Up to 5 × 10(5) photopulse intervals can be recorded at a maximum rate of approximately 2 × 10(5) data points/s. A short description of the algorithms used to calculate the different functions is given together with some useful hints and a table of typical processing times.

Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.

Falls in gastric intramucosal pH (pHi) are associated with morbidity and mortality in patients admitted to intensive-care units (ICU). We tested the hypothesis that ICU outcome can be improved by therapy guided by changes in pHi and aimed at improving systemic oxygen availability. We studied 260 patients admitted to ICUs with APACHE II scores of 15-25. After insertion of a gastric tonometer, each patient was randomly assigned to a control or protocol group within the admission pHi category (normal = 7.35 or higher; low = below 7.35). The control groups were treated according to standard ICU practices. The protocol groups received, in addition, treatment to increase systemic oxygen transport or to reduce oxygen demand, whenever the pHi fell below 7.35 or by more than 0.10 units from the previous measurement. The protocol was used, because pHi fell, in 67 (85%) of the protocol group with normal pHi on admission. There were no significant differences between protocol and control groups in demographic characteristics, admission blood gases or haemoglobin concentration, number or type of organ system failures, or the intensity of ICU care. For patients admitted with low pHi, survival was similar in the protocol and control groups (37% vs 36%), whereas for those admitted with normal pHi, survival was significantly greater in the protocol than in the control group (58% vs 42%; p less than 0.01). Therapy guided by pHi measurements improved survival in patients whose pHi on admission to ICU was normal. pHi-guided resuscitation may help improve outcome in such patients by preventing splanchnic organ hypoxia and the development of a systemic oxygen deficit.

Efecto agudo del salbutamol intravenoso en el estado de mal asmático / Acute effect of intravenous salbutamol in status asthmaticus

Para evaluar el efecto broncodilatador del salbutamol por vía intravenosa en el estado de mal asmático, se estudiaron 20 pacientes internados por dicha causa en un servicio de terapia intensiva. Todos los pacientes seleccionados tenían un FEV menor del 30% del valor teórico y una PaO respirando aire menor de 69mmHg. Como criterio adicional de severidad, ninguno de ellos tuvo respuesta broncodilatadora luego de una nebulización de 5mg de salbutamol. Diez pacientes (grupo 1) recibieron una inyección intravenosa rápida (1min) de 0,2mg de salbutamol y los 10 restantes (grupo 2) una infusión continua durante 1h de 0,5mg de salbutamol. Los 20 pacientes fueron seguidos con medicaciones cada 10min de FEV, FVC, frecuencia cardíaca, tensión arterial sistólica y diastólica y amplitud del pulso paradojal durante 1h. La infusión continua de salbutamol produjo cambios estadísticamente significativos del FEV a partir de los 40min de infusión y de la FVC a partir de los 5min. La inyección intravenosa no produjo efectos broncodilatadores significativos. En ambos grupos se observó un descenso significativo de la tensión arterial sistólica y diastólica y de la amplitud del pulso paradojal y un ascenso de la frecuencia cardíaca. Se analizan los resultados y se concluye que la infusión de salbutamol es de utilidad en el tratamiento inicial del mal asmático en tanto actúan los corticosteroides (AU)

Hematoma mediastinal causante de severa compresión de la vía aérea / Mediastinal hematoma causing severe airway compression

Presentamos el caso de una paciente de 43 años que ingresó al Centro Respiratorio por presentar un cuadro de asma grave, anemia severa y acidosis metabólica. Durante la ARM se detectó una masa mediastinal que comprimía la tráquea y que en la tomografía computada tenía densidad de tejidos sólidos. Previamente se había colocado un catéter central por punción de la vena yugular interna. La paciente falleció y en la autopsia se evidenció un hematoma mediastinal compresivo que se atribuyó a la punción. Se destacan el error diagnóstico cometido, por las características tomográficas del hematoma, y la génesis de una causa infrecuente de obstrucción de la vía aérea como complicación de un procedimiento cuya peligrosidad no fue adecuadamente valorada en relación a los trastornos de coagulación pre-existentes (AU)