The efficient physiological strategy of a novel tomato genotype to adapt to chronic combined water and heat stress.

Climate change is increasing the frequency of high temperature shocks and water shortages, pointing to the need to develop novel tolerant varieties and to understand the mechanisms employed to withstand combined abiotic stresses. Two tomato genotypes, a heat-tolerant Solanum lycopersicum accession (LA3120) and a novel genotype (E42), previously selected as a stable yielding genotype under high temperatures, were exposed to single and combined water and heat stress. Plant functional traits, pollen viability and physiological (leaf gas exchange and chlorophyll a fluorescence emission measurements) and biochemical (antioxidant content and antioxidant enzyme activity) measurements were carried out. A Reduced Representation Sequencing approach allowed exploration of the genetic variability of both genotypes to identify candidate genes that could regulate stress responses. Both abiotic stresses had a severe impact on plant growth parameters and on the reproductive phase of development. Growth parameters and leaf gas exchange measurements revealed that the two genotypes used different physiological strategies to overcome individual and combined stresses, with E42 having a more efficient capacity to utilize the limiting water resources. Activation of antioxidant defence mechanisms seemed to be critical for both genotypes to counteract combined abiotic stresses. Candidate genes were identified that could explain the different physiological responses to stress observed in E42 compared with LA3120. Results here obtained have shown how new tomato genetic resources can be a valuable source of traits for adaptation to combined abiotic stresses and should be used in breeding programmes to improve stress tolerance in commercial varieties.

A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

OBJECTIVE: Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS: In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS: Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS: Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Sequential monitoring and stability of ex vivo-expanded autologous and nonautologous regulatory T cells following infusion in nonhuman primates.

Ex vivo-expanded cynomolgus monkey CD4(+)CD25(+)CD127(-) regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-specific demethylation region, and potently suppressed T cell proliferation through three rounds of expansion. When carboxyfluorescein succinimidyl ester- or violet proliferation dye 450-labeled autologous (auto) and nonautologous (non-auto)-expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 postinfusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these nontransplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of nonhuman primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites.

Ex vivo-expanded cynomolgus macaque regulatory T cells are resistant to alemtuzumab-mediated cytotoxicity.

Alemtuzumab (Campath-1H) is a humanized monoclonal antibody (Ab) directed against CD52 that depletes lymphocytes and other leukocytes, mainly by complement-dependent mechanisms. We investigated the influence of alemtuzumab (i) on ex vivo-expanded cynomolgus monkey regulatory T cells (Treg) generated for prospective use in adoptive cell therapy and (ii) on naturally occurring Treg following alemtuzumab infusion. Treg were isolated from PBMC and lymph nodes and expanded for two rounds. CD52 expression, binding of alemtuzumab and both complement-mediated killing and Ab-dependent cell-mediated cytotoxicity (ADCC) were compared between freshly isolated and expanded Treg and effector T cells. Monkeys undergoing allogeneic heart transplantation given alemtuzumab were monitored for Treg and serum alemtuzumab activity. Ex vivo-expanded Treg showed progressive downregulation of CD52 expression, absence of alemtuzumab binding, minimal change in complement inhibitory protein (CD46) expression and no complement-dependent killing or ADCC. Infusion of alemtuzumab caused potent depletion of all lymphocytes, but a transient increase in the incidence of circulating Treg. After infusion of alemtuzumab, monkey serum killed fresh PBMC, but not expanded Treg. Thus, expanded cynomolgus monkey Treg are resistant to alemtuzumab-mediated, complement-dependent cytotoxicity. Furthermore, our data suggest that these expanded monkey Treg can be infused into graft recipients given alemtuzumab without risk of complement-mediated killing.

Too fast, too soon to call it "probiotic".

Probiotics (bacteria or yeasts) were defined by the Food Agricultural Organization (FAO) and the World Health Organization (WHO) joint report as live microorganisms which when administered in adequate amounts (in food or as a dietary supplement) confer a health benefit on the host. The best-demonstrated potential clinical benefits of probiotic agents, specifically in the pediatric population, are in the prevention and management of acute diarrhea, antibiotic associated diarrhea, and evidence is mounting on their potential benefits in atopic disease, inflammatory bowel conditions, and necrotizing enterocolitis. Their beneficial effects seem to be strain specific, thus, pooling data from different strains may result in misleading conclusions. Because there was no international consensus on methodology to assess efficiency and safety of probiotics, in 2001 the FAO/WHO undertook work to compile and evaluate the scientific evidence on functional and safety aspects of probiotics. International criteria have been developed to formulate unequivocal criteria for probiotic bacterial strains and products that contain them. More recently, the European Food Safety Authority (EFSA) highlighted as critical factors for probiotic health claim submissions genetic typing, internationally recognised naming protocols and evidence of consistency in the final product.

Long-term efficacy of botulinum toxin A for treatment of blepharospasm, hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes.

PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation.

Delivery of rapamycin to dendritic cells using degradable microparticles.

Degradable microparticles have the potential to protect and release drugs over extended periods and, if sized appropriately, can be passively targeted to phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells known to play important roles in transplant rejection. Previously, we have demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the ability to suppress transplant rejection. Herein, we describe a strategy to deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was encapsulated into ~3.4 microm sized poly(lactic-co-glycolic)acid (PLGA) microparticles (rapaMPs), and release behavior was examined under intra-phagosomal (pH=5) and extracellular (pH=7.4) conditions. It was observed that 4 days following phagocytosis of rapaMP, DC have significantly reduced ability to activate T cells, in comparison to DC treated with soluble rapamycin. Hence, we conclude that DC-specific intracellular delivery of rapamycin results in better efficacy of the drug, with respect to its ability to modulate DC function, when compared to treating DC with extracellular rapamycin.

Consenso argentino de ventilación no invasiva / Argentine consensus of non-invasive ventilation

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.

La ventilación no invasiva (VNI) ha alcanzado notable difusión en los últimos años. El ahorro delas complicaciones causadas por la intubación traqueal la hace especialmente atractiva en pacientesque presentan insuficiencia respiratoria aguda (IRA) no muy grave y que conservan cierta autonomía respiratoria.También se han descripto efectos terapéuticos en pacientes con insuficiencia respiratoria crónica de etiologías diversas. No obstante, los resultados obtenidos son variables según las circunstancias que motivan su aplicación. A fin de revisar la evidencia a favor de su uso se elaboró este Consenso referido particularmente a la VNI a presión positiva. Se describen su fundamento fisiopatológico, esencial para su correcta aplicación, y elequipamiento necesario para implementarla. La evidencia existente en la literatura establece definida utilidad de la VNI en la exacerbación de la EPOC y en el edema agudo de pulmón cardiogénico (Recomendación A).Su beneficio es aún incierto en pacientes con IRA secundaria a síndrome de dificultad respiratoria aguda, salvoen el subgrupo de pacientes inmunosuprimidos (Recomendación B). Los resultados son también favorablesen la desvinculación de la asistencia respiratoria mecánica (ARM), especialmente en pacientes ventilados por exacerbación de EPOC (Recomendación A). En la insuficiencia respiratoria crónica se ha hallado mejoría en la calidad de vida y mayor sobrevida en pacientes con enfermedades restrictivas (Recomendación B), mientrasque existe aún controversia sobre su utilidad en pacientes con EPOC estable (Recomendación C). La VNI debeser aplicada con estándares de cuidados que son establecidos. Se revisan las eventuales complicaciones derivadasde su uso y el beneficio costo-efectividad ahorrando recursos de mayor complejidad y disminuyendolos riesgos que implica la ARM invasiva.

Consenso argentino de ventilación no invasiva / Argentine consensus of non-invasive ventilation

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.(AU)

La ventilación no invasiva (VNI) ha alcanzado notable difusión en los últimos años. El ahorro delas complicaciones causadas por la intubación traqueal la hace especialmente atractiva en pacientesque presentan insuficiencia respiratoria aguda (IRA) no muy grave y que conservan cierta autonomía respiratoria.También se han descripto efectos terapéuticos en pacientes con insuficiencia respiratoria crónica de etiologías diversas. No obstante, los resultados obtenidos son variables según las circunstancias que motivan su aplicación. A fin de revisar la evidencia a favor de su uso se elaboró este Consenso referido particularmente a la VNI a presión positiva. Se describen su fundamento fisiopatológico, esencial para su correcta aplicación, y elequipamiento necesario para implementarla. La evidencia existente en la literatura establece definida utilidad de la VNI en la exacerbación de la EPOC y en el edema agudo de pulmón cardiogénico (Recomendación A).Su beneficio es aún incierto en pacientes con IRA secundaria a síndrome de dificultad respiratoria aguda, salvoen el subgrupo de pacientes inmunosuprimidos (Recomendación B). Los resultados son también favorablesen la desvinculación de la asistencia respiratoria mecánica (ARM), especialmente en pacientes ventilados por exacerbación de EPOC (Recomendación A). En la insuficiencia respiratoria crónica se ha hallado mejoría en la calidad de vida y mayor sobrevida en pacientes con enfermedades restrictivas (Recomendación B), mientrasque existe aún controversia sobre su utilidad en pacientes con EPOC estable (Recomendación C). La VNI debeser aplicada con estándares de cuidados que son establecidos. Se revisan las eventuales complicaciones derivadasde su uso y el beneficio costo-efectividad ahorrando recursos de mayor complejidad y disminuyendolos riesgos que implica la ARM invasiva.(AU)

Difficult diagnosis of infliximab-related miliary tuberculosis.

The use of Infliximab in the treatment of patients with rheumatoid diseases unresponsive to conventional therapies has been reported to be complicated by opportunistic infections. We report the case of a 56-yr old female rheumatoid arthritis patient complaining of fever and respiratory symptoms 9 months after commencing Infliximab, who received no ethiologic diagnosis for the six months before admission. Tuberculosis was suspected upon chest radiographic pictures and empirical treatment for miliary tuberculosis instated in the wake of microbiological confirmation. The case typifies the difficulties of diagnosing miliary tuberculosis in the immunocompromised as well as in the immunocompetent patient.

Neuroendocrine changes involved in the genesis of HD-induced orthostatic intolerance.

The aim of the present study was to analyze the role played by norepinephrine and epinephrine in Symptomatic (S) vs Non-Symptomatic (NS) subjects within a group of healthy volunteers undergoing a 4-hour-head-down bed rest study at -6 degrees.

Head-down bed rest reduces the breathing rate short-term variability in subjects with orthostatic intolerance.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity. We have showed that in symptomatic subjects the baroreflex control of sinus node is affected by short term simulated microgravity. At present the influence of the respiration on the cardiovascular system in this condition is not clear. The aim of the present study was to examine the behaviour of the Breathing Rate (BR) in 5 Non-Symptomatic (NS) and 3 Symptomatic (S) subjects before and after 4 hours of head-down bed rest (HD).

Encuesta a neumonologos sobre el diagnostico y tratamiento de EPOC / Survey of chest physicians regarding COPD diagnosis and treatment

A survey on COPD diagnostic procedures, treatment and management was conducted in a group of 517 chest physicians randomized from a list of the 1121 affiliates to the Asociación Argentina de Medicina Respiratoria. One hundred eighty-seven responses were obtained (36.2% of the questionnaires mailed). They treat an average of 53.3 COPD patients every month. Twenty-four percent of them had mild, 41.8% moderate and 33.8% severe disease (GOLD criteria). Only clinical criteria for diagnosis of COPD, clinical criteria + spirometry (S), and clinical criteria + S + chest X ray were used by 2.9, 23.4 and 73.7% of responders, respectively. Seventy percent of responders believed that chronic asthma without bronchodilator response must be included in the COPD definition. Only 14.1% of responders performed S in every office visit. Cardiac function was assessed using clinical criteria, electrocardiogram and echocardiogram by 90.6, 80.6 and 73.8% of responders, respectively, while 98.3% stated that they trained most of their patients in the inhalation technique. Metered Dose Inhaled was the first option for bronchodilators administration (64.8%) followed by nebulization (16.5%), dry powder inhalation (13.7%) and oral administration (4.8%). First option for chronic therapy in severe COPD patients was the association of anticholinergic drug (AC) + short acting beta2-agonists (SABA) (65.5%), AC alone (18.8%), long acting beta2-agonists (LABA) (9.7%), inhaled corticosteroids (IC) (3.5%) and SABA alone (2.8%). Corticosteroids and antibiotics were prescribed in severe COPD exacerbation by 92.5 and 70% of responders, respectively. First choice antibiotic formulation was beta-lactamics + beta-lactamase inhibitors in 39% of the responders followed by fluorquinolones in 23.7%, macrolides in 17.5% and beta-lactamics in 12.5%. Lastly, 12.7% of COPD patients received long-term domiciliary oxygen therapy. 59.3% of them were prescribed pulmonary rehabilitation, 94.1% vaccination against in...

Se realizo una encuesta acerca de diagnostico y tratamiento de EPOC a un grupo de 517 especialistasen neumonologia, seleccionados al azar entre los 1121 integrantes de la Asociacion Argentina de Medicina Respiratoria. Se obtuvieron 187 respuestas (36.2%). Atienden en promedio 53.3 pacientes con EPOC/mes, a los cuales definen como leves el 24.2%, moderados el 41.8% y severos el 33.8% (criterios normativos GOLD).El criterio utilizado para el diagnostico de EPOC fue solo clinico en el 2.9%, clinico y espirometria (ESP) en el 23.4%y clinico, ESP y por imagenes en el 73.7%. El 70.1% de los encuestados incluye dentro de la definicion de EPOC al asma cronico de escasa respuesta a broncodilatadores. Solo el 14.1% manifiesta realizar espirometria en cada consulta. La evaluacion de la funcion cardiaca la realizan en EPOC severa por examen clinico (90.6%), electrocardiograma (80.6%) y ecocardiograma (73.8%). El 98.3% de los encuestados afirma que la mayoria de los pacientes son instruidosen la realizacion de maniobras de inhalacion de medicamentos. Eligieron como primera opcion para administrarbroncodilatadores en aerosol (64.8%), nebulizacion (16.5%), polvo (13.7%) y via oral (4.8%). El 65.5% eligio comoprimera opcion de tratamiento cronico a los anticolinergicos (AC) + beta2-agonistas de acción corta (BAAC), 18.8% ACsolos, 9.7% beta2-agonistas de accion larga (BAAL), 3.5% corticoides inhalados (CI) y 2.8% BAAC solos. Los corticoides sistemicos y los antibioticos fueron utilizados en las reagudizaciones severas por el 92.5% y el 70% de los encuestados, respectivamente. En esa situacion, como antibioticos de primera eleccion, fueron elegidos los beta lactamicos + inhibidores de beta-lactamasa por el 39.1% de los encuestados, fluorquinolonas (23.7%), macrolidos (17.4%) y betalactamicos...

Encuesta a neumonologos sobre el diagnostico y tratamiento de EPOC / Survey of chest physicians regarding COPD diagnosis and treatment

A survey on COPD diagnostic procedures, treatment and management was conducted in a group of 517 chest physicians randomized from a list of the 1121 affiliates to the Asociación Argentina de Medicina Respiratoria. One hundred eighty-seven responses were obtained (36.2% of the questionnaires mailed). They treat an average of 53.3 COPD patients every month. Twenty-four percent of them had mild, 41.8% moderate and 33.8% severe disease (GOLD criteria). Only clinical criteria for diagnosis of COPD, clinical criteria + spirometry (S), and clinical criteria + S + chest X ray were used by 2.9, 23.4 and 73.7% of responders, respectively. Seventy percent of responders believed that chronic asthma without bronchodilator response must be included in the COPD definition. Only 14.1% of responders performed S in every office visit. Cardiac function was assessed using clinical criteria, electrocardiogram and echocardiogram by 90.6, 80.6 and 73.8% of responders, respectively, while 98.3% stated that they trained most of their patients in the inhalation technique. Metered Dose Inhaled was the first option for bronchodilators administration (64.8%) followed by nebulization (16.5%), dry powder inhalation (13.7%) and oral administration (4.8%). First option for chronic therapy in severe COPD patients was the association of anticholinergic drug (AC) + short acting beta2-agonists (SABA) (65.5%), AC alone (18.8%), long acting beta2-agonists (LABA) (9.7%), inhaled corticosteroids (IC) (3.5%) and SABA alone (2.8%). Corticosteroids and antibiotics were prescribed in severe COPD exacerbation by 92.5 and 70% of responders, respectively. First choice antibiotic formulation was beta-lactamics + beta-lactamase inhibitors in 39% of the responders followed by fluorquinolones in 23.7%, macrolides in 17.5% and beta-lactamics in 12.5%. Lastly, 12.7% of COPD patients received long-term domiciliary oxygen therapy. 59.3% of them were prescribed pulmonary rehabilitation, 94.1% vaccination against in...(AU)

Se realizo una encuesta acerca de diagnostico y tratamiento de EPOC a un grupo de 517 especialistasen neumonologia, seleccionados al azar entre los 1121 integrantes de la Asociacion Argentina de Medicina Respiratoria. Se obtuvieron 187 respuestas (36.2%). Atienden en promedio 53.3 pacientes con EPOC/mes, a los cuales definen como leves el 24.2%, moderados el 41.8% y severos el 33.8% (criterios normativos GOLD).El criterio utilizado para el diagnostico de EPOC fue solo clinico en el 2.9%, clinico y espirometria (ESP) en el 23.4%y clinico, ESP y por imagenes en el 73.7%. El 70.1% de los encuestados incluye dentro de la definicion de EPOC al asma cronico de escasa respuesta a broncodilatadores. Solo el 14.1% manifiesta realizar espirometria en cada consulta. La evaluacion de la funcion cardiaca la realizan en EPOC severa por examen clinico (90.6%), electrocardiograma (80.6%) y ecocardiograma (73.8%). El 98.3% de los encuestados afirma que la mayoria de los pacientes son instruidosen la realizacion de maniobras de inhalacion de medicamentos. Eligieron como primera opcion para administrarbroncodilatadores en aerosol (64.8%), nebulizacion (16.5%), polvo (13.7%) y via oral (4.8%). El 65.5% eligio comoprimera opcion de tratamiento cronico a los anticolinergicos (AC) + beta2-agonistas de acción corta (BAAC), 18.8% ACsolos, 9.7% beta2-agonistas de accion larga (BAAL), 3.5% corticoides inhalados (CI) y 2.8% BAAC solos. Los corticoides sistemicos y los antibioticos fueron utilizados en las reagudizaciones severas por el 92.5% y el 70% de los encuestados, respectivamente. En esa situacion, como antibioticos de primera eleccion, fueron elegidos los beta lactamicos + inhibidores de beta-lactamasa por el 39.1% de los encuestados, fluorquinolonas (23.7%), macrolidos (17.4%) y betalactamicos...(AU)

Mutual information detects a decreased interdependence between RR and SAP in orthostatic intolerance after microgravity condition.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity. However, the exact mechanisms underlying these alterations have not been completely clarified. Several methods for studying the time series of systolic arterial pressure and RR interval have been proposed both in the time and in the frequency domain. However, these methods did not produce definitive results. In fact heart rate and arterial pressure show a complex pattern of global variability which is likely due to non linear feedback which involves the autonomic nervous system and to "stochastic" influences. Aim of this study was to evaluate the degree of interdependence between the mechanisms responsible for the variability of SAP and RR signals in subjects exposed to head down (HD). This quantification was achieved by using Mutual Information (MI).

Autoreactive isotype-specific T cells determine B cell frequency.

Suppressive activities involving T-B and T-T cell interactions are important to maintain immune system homeostasis. Negative control of IgG2ab+ B cells by anti-IgG2ab T cells derived from Igha mice has been well documented. Nevertheless the real contribution of anti-IgG2ab T cells, endogenously matured in Ighb mice, in controlling IgG2ab+ B cell function has never been investigated. We previously generated anti-IgG2ab TCR-transgenic mice and showed that transgenic T cells were not deleted in the thymus and that they were responsible for a complete and chronic IgG2ab suppression. Here we show that T cells expressing high density of anti-IgG2ab TCR were positively selected in the thymus with a higher efficiency in animals expressing IgG2ab, reached peripheral lymphoid organs and negatively controlled IgG2ab serum levels. Moreover, anti-IgG2ab T cells transgenic for the single TCR chain, thus undergoing normal rearrangements and normal processes of selection, also reached the periphery and suppressed IgG2ab. Interestingly, concentration of IgG2ab in serum inversely correlated with the peripheral frequency of Ig-specific T cells. Finally, T cells able to suppress IgG2ab were obtained from Ighb non-transgenic mice, indicating that anti-2ab T cells are naturally present in the periphery of Ighb animals. We propose that IgG2ab-specific T cells contribute to determine IgG2ab serum levels in Ighb mice.

Positive and negative feedback mechanisms in the neural regulation of cardiovascular function in healthy and spinal cord-injured humans.

BACKGROUND: We tested the hypothesis that in humans, hypertension/tachycardia and hypotension/bradycardia nonbaroreflex sequences that occur within spontaneous arterial pressure (AP) and R-R interval fluctuations are an expression of positive feedback mechanisms neurally regulating the cardiovascular system. METHODS AND RESULTS: We studied 15 spinal cord-injured (SCI) subjects (8 tetraplegics and 7 paraplegics) and 8 healthy subjects. The occurrence of nonbaroreflex (NBseq) and baroreflex (Bseq) sequences, ie, hypertension-bradycardia and hypotension-tachycardia sequences, was assessed during rest and head-up tilt (HUT). The ratio between Bseq and NBseq (B/NB ratio) was also calculated. In resting conditions, the occurrence of NBseq was significantly lower (P:<0.05) in tetraplegics (7.9+/-1.5) than in paraplegics (16.2+/-3.2) and normal subjects (19.0+/-3.5), whereas the occurrence of Bseq was not significantly different between the 3 groups (38.6+/-11.9 versus 45.4+/-6.0 versus 47.0+/-11.9). In tetraplegics, the B/NB ratio showed a marked, significant decrease (from 8.4+/-4.2 to 1.9+/-0.8, P:<0.05) in response to HUT, whereas in normal subjects, it showed a significant increase (from 3.5+/-0.7 to 9.4+/-2.7, P:<0.05). In paraplegics, the B/NB ratio did not change significantly in response to HUT (from 4.5+/-1.6 to 4.8+/-1.1). CONCLUSIONS: Our data suggest that nonbaroreflex sequences occur in humans and might represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation that is able to interact dynamically with feedback mechanisms of baroreflex origin.

Average magnitude of heartbeat fluctuations in healthy subjects after exposure to 4 hours head down bed rest.

Orthostatic intolerance, induced by microgravity exposure, has been hypothesized to be related to a disorder of the autonomic control of the cardiovascular system. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of the autonomic system to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microG. These differences seem to be due to different experimental designes used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some role in producing these discrepancies [correction of dicrepancies]. In this study we suggest the analysis of "magnitude" or "volatility" as a new method to study HRV variability. The volatility is a measure of the beat-to-beat excursion capability of the heart, regardless to its direction (positive or negative): the higher the volatility, the greater the excursion. The aim of the present study was to examine R-R volatility before and after 4 hours of HD -6 degrees in normal subjects.

Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease: A randomized, controlled study.

BACKGROUND: Myocardial ischemia and infarction impair baroreflex sensitivity (BRS), which when depressed is predictive of future cardiac events after myocardial infarction (MI). The main objective of this study was to determine whether exercise training improves BRS in patients with coronary artery disease. METHODS AND RESULTS: Ninety-seven male patients with and without a previous MI were recruited after myocardial revascularization surgery and randomized into trained (TR) or untrained (UTR) groups. TR patients underwent a residential exercise program at 85% of maximum heart rate (HRmax) consisting of 2 daily sessions 6 times a week for 2 weeks. Eighty-six patients (45 TR and 41 UTR) completed the study. BRS was assessed at baseline and at the end of the protocol by the spontaneous baroreflex method. The standard deviation of mean R-R interval (RRSD) was also assessed as a measure of heart rate variability. At baseline, there were no significant differences between TR and UTR patients in any variable. In TR patients, BRS increased from 3.0+/-0.3 to 5.3+/-0.7 ms/mm Hg (P:<0.001), RRSD from 18.7+/-1.4 to 23.6+/-1.6 ms (P:<0.01), and R-R interval from 792. 0+/-15.5 to 851.3+/-20.5 ms (P:<0.001). No significant changes occurred in UTR patients. Increases in BRS and RRSD were significant in patients either with or without a previous MI. CONCLUSIONS: Exercise training increases BRS and heart rate variability in patients with coronary artery disease. Improved cardiac autonomic function might add to the other benefits of exercise training in secondary prevention of ischemic heart disease.