Identification of soybean genotypes with high stability for the Brazilian macro-region 402 via biplot analysis.

Biplot analysis has often been used to recommend genotypes from different crops in the presence of the genotype x environment interaction (GxE). The objective of this study was to verify the association between the AMMI and GGE biplot methods and to select soybean genotypes that simultaneously meet high grain yield and stability to the environments belonging to the Edaphoclimatic Region 402, from Soybean Cultivation Region 4 (Mid-West), which comprises the Center North and West of Mato Grosso, and the southern region of Rondônia. Grain yield of 12 soybean genotypes was evaluated in seven competition trials of soybean cultivars in the 2014/2015 harvest. Significant GxE interaction revealed the need to use methods for recommending genotypes with adaptability and yield stability. The methods were complementary regarding the recommendation of the best genotypes. The AMMI analysis recommended MG/BR46 (Conquista) (G10) widely for all environments evaluated, whereas the BRY23-55012 (G9) and BRAS11-0149 (G2) were the most indicated genotypes by the GGE biplot method. However, the methods were concordant as to Porto Velho (PV1) environment that contributed least to the GxE interaction.

Inbreeding depression in single, three way and double-cross hybrids of maize.

Currently, one of the acclaimed alternatives for increasing maize yield is accomplished through utilization of heterosis in hybrid cultivars. However, upon performing crosses between related pairs, there are losses due to inbreeding depression. Thus, the aim of this study was to estimate inbreeding depression and the contribution of loci in heterozygosity in different types of maize hybrids. Eight treatments were evaluated, considering the F1 and S0 generations of four commercial hybrids. A randomized block experimental design was used, with three replications, and plots consisting of two three-meter long rows at a spacing of 0.50 m. The traits evaluated were plant height, first ear height and husked ear weight. For ear weight trait, there was a significant difference, where the treatments could be classified into three distinct groups. In this case, the single-cross hybrids AG7088 and 30F90Y exhibited greater depression through inbreeding due to the greater contribution of loci in heterozygosity and consequent predominance of deviations due to dominance.

Adaptability and phenotypic stability of soybean cultivars for grain yield and oil content.

The aim of this study was to verify the adaptability and stability of soybean cultivars with regards to yield and oil content. Data of soybean yield and oil content were used from experiments set up in six environments in the 2011/12 and 2012/13 crop seasons in the municipalities of Patos de Minas, Uberaba, Lavras, and São Gotardo, Minas Gerais, Brazil, testing 36 commercial soybean cultivars of both conventional and transgenic varieties. The Wricke method and GGE biplot analysis were used to evaluate adaptability and stability of these cultivars. Large variations were observed in grain yield in relation to the different environments studied, showing that these materials are adaptable. The cultivars exhibited significant differences in oil content. The cultivars BRSGO204 (Goiânia) and BRSMG (Garantia) exhibited the greatest average grain yield in the different environments studied, and the cultivar BRSMG 760 SRR had the greatest oil content among the cultivars evaluated. Ecovalence was adopted to identify the most stable cultivars, and the estimates were nearly uniform both for grain yield and oil content, showing a variation of 0.07 and 0.01%, respectively. The GGE biplot was efficient at identifying cultivars with high adaptability and phenotype stability.

Resistance of upland-rice lines to root-knot nematode, Meloidogyne incognita.

Despite the benefits of crop rotation, occurrence of nematodes is a common problem for almost all crops within the Cerrado biome, especially for rice. The use of resistant cultivars is one of the main methods for control of nematodes. Thus, the present study aimed to evaluate the reaction of 36 upland-rice lines, with desirable agronomic characteristics, according to their resistance to root-knot nematodes (Meloidogyne incognita). The experimental design was entirely randomized with four replications. Each plot of land consisted of two rice plants in a 3-L vase. The plants were inoculated with 1000 eggs and eventual juveniles of the respective nematodes. Fifty-five days after the inoculation, the roots and the aerial part of the plant were weighed and the egg mass (EM) as well as the reproduction factor (Rf) were estimated. It was determined that the isolated use of EM was not beneficial in selecting rice lines resistant to the root-knot nematode. This procedure must, therefore, take into account the egg counting and the Rf, in order to improve the reliability of the selection. In our study, 30 evaluated lines were observed to be resistant. Among the recommended cultivars, only BRS Monarca had its performance susceptible to the studied nematode species.

Effects of maternal diabetes on male offspring: high cell proliferation and increased activity of MMP-2 in the ventral prostate.

This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor ß1 (TGFß-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in α-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGFß-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGFß-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.

Pesquisa e atividades de extensão em fitoterapia desenvolvidas pela Rede FitoCerrado: uso racional de plantas medicinais e fitoterápicos por idosos em Uberlândia-MG / Research and extension activities in herbal medicine developed by Rede FitoCerrado: rational use of medicinal plants by the elderly in Uberlândia-MG

Este estudo objetivou realizar atividades de extensão em fitoterapia, a partir de um levantamento de dados sobre as plantas medicinais, fitoterápicos e medicamentos convencionais utilizados por 292 idosos frequentadores de um programa de Atividades Físicas e Recreativas para a Terceira Idade (AFRID), na cidade de Uberlândia-MG, utilizando como instrumento de investigação, um questionário semiestruturado. Dentre os entrevistados verificamos que 88% utilizavam medicamentos prescritos, principalmente para o controle da hipertensão. O uso de plantas medicinais foi relatado por 76,7% dos idosos, sendo as mais citadas: Cymbopogon citratus, Mentha sp., Rosmarinus officinalis, Plectranthus barbatus, Ocimum gratissimum, e Matricaria chamomilla. Dezesseis (5,5%) idosos utilizavam fitoterápicos, principalmente preparados a partir de extratos de Ginkgo biloba, Aesculus hippocastanum e Passiflora incarnata em associação com Crataegus oxyacantha e Salix alba. O uso concomitante de plantas medicinais e fitoterápicos com medicamentos convencionais foi relatado por 86,2% e 81,3% dos idosos, respectivamente. Após a análise dos dados percebemos a necessidade do desenvolvimento de ações educativas para informar e conscientizar os idosos sobre o uso da fitoterapia. Elaboramos uma caderneta e uma cartilha para promoção da difusão dessas informações e o aprimoramento do uso da fitoterapia entre os idosos e, dessa forma, alcançar os profissionais de saúde sobre os riscos e benefícios dessa terapêutica; contribuindo assim para o uso seguro e racional da fitoterapia.

This study aimed to carry out extension activities in herbal medicine from a survey of data on medicinal plants, herbal and conventional medicines used by 292 elderly people who attended a program of physical activity called Physical and Recreational Activities for the Elderly, in Uberlândia-MG, using a semi-structured questionnaire as means of investigation. Among the respondents 88% used prescription drugs, primarily for control of hypertension. The use of medicinal plants was reported by 76.7% of the elderly, being the most cited ones: Cymbopogon citratus, Mentha sp., Rosmarinus officinalis, Plectranthus barbatus, Ocimum gratissimum. and Matricaria chamomilla. Sixteen respondents (5,5%) used herbal medicines, especially those prepared from extracts of Ginkgo biloba, Aesculus hippocastanum, and Passiflora incarnata L. in association with Crataegus oxyacantha L. and Salix alba. The concomitant use of medicinal plants and herbal medicines with conventional drugs was reported by 86.2% and 81.3% of participants, respectively. After analyzing the data, we detected the need to develop educational activities to inform and educate seniors about the use of herbal medicine, encompassing the development a book and a primer for initial dissemination of this information, improving herbal medicine use among the elderly. This course of action would allow a greater knowledge of health professionals about the risks and benefits of this therapy, thereby contributing to the safe and rational use of herbal medicine.

The influence of different metabolic syndrome definitions in predicting vasculogenic erectile dysfunction: is there a role for the index of central obesity?

AIMS: Analyze the capacity of ICO, the ratio of waist circumference (WC) and height, in predicting hemodynamic impairment in Erectile Dysfunction (ED) patients, independently and integrated in Metabolic Syndrome (MetS) definitions. METHODS: Four hundred and eighty-five ED patients followed in Urology consult from January 2008 until March 2012 were evaluated by a standardized protocol: health questionnaire, anthropometric measurements (AM), blood pressure and analysis, and Penile Duplex Doppler Ultrasound (PDDU) exam. Associations between AM and MetS definitions, including ATPIII, IDF and a new definition replacing WC by ICO in ATPIII MetS definition (ModATPIII), and PDDU were calculated. RESULTS: ICO was the measure of obesity more strongly correlated with diminished mean Peak Systolic Velocity (mPSV) (r = -0.189, p < 0.001). A positive association remained when replacing WC by ICO ≥ 0.60 (a nationally obtained ratio) in ATPIII MetS definition (ModATPIII). Patients with ModATPIII had lower mPSV when compared to non-MetS patients (30.8 versus 37.1, p < 0.001). Only the IDF definition had a significant association with AD (OR = 1853; 95%CI, 1.202-2.857). CONCLUSIONS: ICO revealed potential value to predict PDDU changes in a MetS context. However, IDF definition presented a stronger correlation with arteriogenic ED. Although longitudinal studies are necessary to confirm this hypothesis, our study highlights the importance of different MetS definitions for ED assessment.

Endothelial function in patients with metabolic syndrome and erectile dysfunction: a question of angiopoietin imbalance?

Erectile dysfunction (ED) is a highly prevalent disease whose aetiology is mostly vasculogenic. It is nowadays considered a marker of future cardiovascular events reflecting the underlying endothelial dysfunction, the common link with the metabolic syndrome (MetS). The recent association between MetS, endothelial dysfunction and peripheral artery disease, but not with coronary artery disease (CAD), suggests that the pathophysiologies of CAD and peripheral artery disease may be distinct. Moreover, several recent studies support an emerging role for an imbalance of angiogenic growth factor levels like Angiopoietin 1 and 2 in cardiovascular disease, considering its intimate association with chronic low-grade inflammation. We aim to find a correlation between Angiopoietins levels and systemic and local endothelial function in MetS and ED patients. Forty-five MetS patients with ED were enrolled. ED severity was assessed by International Index of Erectile Function questionnaire (IIEF5) and penile duplex Doppler ultrasound (PDDU). Endothelial function was assessed by Peripheral arterial tonometry (PAT), and serum asymmetric dimethylarginine (ADMA), Ang1 and Ang2 levels. Obesity and hypertension were the most frequent MetS parameters (91.1 and 88.9% respectively). Severe ED was present in 35.6% of patients. Penile haemodynamic was impaired in 77.5%. Endothelial dysfunction (PAT criteria) was present in 40.9% of patients. Ang2 levels were significantly higher in men with abdominal obesity. We observed an inverse correlation between Ang1 and peak systolic velocity, and in patients with penile arterial dysfunction, Ang1 levels were significantly higher and Ang2/Ang1 ratio significantly lower, than patients with normal arterial function. Neither ADMA nor PAT parameters were correlated with ED severity evaluated by IIEF5 or PDDU exam. In conclusion, there is an imbalance of angiopoietins in MetS and ED patients. The absence of correlation with PAT or ADMA levels suggests that angiopoietins may be early markers of endothelial dysfunction in this population of higher cardiovascular risk.

Model-based patterns in prostate cancer mortality worldwide.

BACKGROUND: Prostate cancer mortality has been decreasing in several high income countries and previous studies analysed the trends mostly according to geographical criteria. We aimed to identify patterns in the time trends of prostate cancer mortality across countries using a model-based approach. METHODS: Model-based clustering was used to identify patterns of variation in prostate cancer mortality (1980-2010) across 37 European, five non-European high-income countries and four leading emerging economies. We characterised the patterns observed regarding the geographical distribution and gross national income of the countries, as well as the trends observed in mortality/incidence ratios. RESULTS: We identified three clusters of countries with similar variation in prostate cancer mortality: pattern 1 ('no mortality decline'), characterised by a continued increase throughout the whole period; patterns 2 ('later mortality decline') and 3 ('earlier mortality decline') depict mortality declines, starting in the late and early 1990s, respectively. These clusters are also homogeneous regarding the variation in the prostate cancer mortality/incidence ratios, while are heterogeneous with reference to the geographical region of the countries and distribution of the gross national income. CONCLUSION: We provide a general model for the description and interpretation of the trends in prostate cancer mortality worldwide, based on three main patterns.

Erectile dysfunction in obstructive sleep apnea syndrome--prevalence and determinants.

INTRODUCTION: OSAS (Obstructive Sleep apnea syndrome) is defined by recurrent episodes of upper airway obstruction during sleep, causing multiple clinical consequences. Literature review suggests that OSAS induces a spectrum of abnormalities in neural, hormonal and vascular regulation that contribute to the development of ED (erectile dysfunction). The aims of this study were to estimate the prevalence of ED in OSAS patients and evaluate its determinants. METHODS: 62 patients from Hospital S. João Sleep Laboratory with newly diagnosed OSAS were included in the study and answered the IIEF-5 (international index erectile function 5 item version) questionnaire. RESULTS: The prevalence of ED in OSAS patients was 64.4%. Age and Diabetes constituted themselves as independent risk factors for more severe degrees of ED: OR=1.226 (95%CI: 1.062-1.415) and OR=31.205 (95%CI: 1.222-796.557), respectively. Compared with nonsmokers, ex-smokers group revealed a positive association with ED: OR=4.32 (95%CI: 1.09-17.11). Hypertension and ACEI (angiotensin converting enzyme inhibitors) or ARB (angiotensin II receptor blockers) therapy were also correlated to ED symptoms: OR=3.25 (95%CI: 1.09-9.65) and 7.39 (95%CI: 1.52-35.99), respectively. No association was found relating BMI (p=0.254), alcoholic habits (p=0.357), acute myocardial infarction (p=0.315), dyslipidemia (p=0.239),metabolic syndrome (p=0.215) and ED. OSAS severity was not associated with ED in our sample. CONCLUSIONS: The prevalence of ED in OSAS patients is high. ED determinants in our sample were age and diabetes. Past smoking habits, hypertension and ACEI/ARB therapy also revealed a statistically significant association with ED.

Predictive factors of a successful testicular biopsy and subsequent clinical pregnancy.

Forecast of success with testicular sperm extraction and intracytoplasmic sperm injection (ICSI) remains unknown, as predictive factors have rarely been studied. We evaluated the association among possible predictive factors and a successful biopsy and clinical pregnancy. A consecutive sample of men submitted to a testicular open biopsy in S. João Hospital was used. Patient's age, medical history, testicular volume, spermogram, genetic testing, endocrinologic results, biopsy results and clinical pregnancy information were collected. From the 113 men included, it was possible to retrieve spermatozoa in 79.6% of the cases, which resulted in 58 fertilisations and 22 clinical pregnancies. Retrieving viable spermatozoa on biopsy was associated with the identification of spermatozoa in the spermogram (100.0% versus 74.4%; P = 0.010), diseases causing obstructive infertility (100.0% versus 79.2%; P = 0.036) and no genetic causes detected (82.4% versus 54.5%; P = 0.030). Successful clinical pregnancy was only associated with lower female partner age (31.7 versus 36.0 year; P = 0.001) but not the quality of the spermatozoa or the time until the reproduction cycle. Identification of spermatozoa in the spermogram, diseases causing obstructive infertility and lack of genetic causes for infertility were associated with higher probability of viable spermatozoa retrieval but the female partner age remained the principal determinant of a successful pregnancy.

Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood.

The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c+ CD11b+ inflammatory dendritic cell and CD8α+ plasmacytoid (pDC) populations that were absent in HDM-exposed infant mice, suggesting an important role in HDM-mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when exposure occurred concurrently with an acute influenza infection; young mice now displayed robust allergen-specific immunity, allergic inflammation, and lung remodeling. Remodeling persisted into early adulthood, even after prolonged discontinuation of allergen exposure and was associated with marked impairment of lung function. Our data demonstrate that allergen exposure coincident with acute viral infection in early life subverts constitutive allergen hyporesponsiveness and imprints an asthmatic phenotype in adulthood.

A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke.

We investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a subchronic exposure model of cigarette smoke (CS)-induced inflammation using antibodies directed against GM-CSF or the GM-CSF receptor (GM-CSFR) α-chain. CS-induced mononuclear and neutrophilic inflammation following 4 days of CS exposure in BALB/c mice was assessed in bronchoalveolar lavage (BAL) fluid. An increase in mature dendritic cells (DCs) (CD11c+ and major histocompatibility complex II+) and Gr-1-high neutrophils was also observed by flow cytometric analysis of whole-lung tissue. Daily i.p. injection of 400 µg GM-CSF or GM-CSFR antibody prior to daily smoke exposure attenuated the accumulation of neutrophils within the BAL by 60%. A reduction in mature DCs was also observed. Anti-GM-CSFR antibody administration did not have an effect on the percentage of lung T-cells; however, a significant decrease in activated CD69+ CD8+ T-cells was observed. Anti-GM-CSFR antibody administration decreased the mRNA and protein expression of interleukin-12 p40 and matrix metalloproteinase 12. Taken together, intervention with this receptor antibody implicates the GM-CSF pathway as an important mediator of smoke-induced inflammation.

Incomplete transposition of the common femoral artery and vein.

Anatomical variations of the great saphenous vein, femoral artery and femoral vein at the inguinal level are rare. Modifications in the anatomical relationships among theses vessel can cause technical difficulties. There are two reports in the literature of the complete transposition of the femoral artery and vein. Both patients had large varicose veins only in the limb that presented the variation, which suggested an extrinsic compression. In the present paper, we report a case study of a patient with an incomplete transposition of the femoral artery and vein. Specifically, the common femoral vein and the saphenofemoral junction were completely overlapped by the common femoral artery. Although this anatomical variation did not present any clinical signs, it required a more complex surgical procedure.

Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability.

Hexavalent chromium [Cr(VI)] is a well-recognized human lung carcinogen. In order to gain further insight into Cr(VI)-induced carcinogenesis, we have established an adequate in vitro cellular model for the study of this process. To this end, BEAS-2B cells were used. Chronic exposure of cells to 1 microM Cr(VI) induced changes in the cells' ploidy and a decrease in cloning efficiency, although cultures continued to progress to confluence. After prolonged exposure (12 passages), the culture became heterogeneous, exhibiting areas where apparently normal epithelial cells and morphologically altered cells coexisted. Subsequent culture at a very low density strongly accentuated the Cr(VI)-induced changes in morphology and pattern of growth. Three individual colonies were then ring-cloned and expanded into three subclonal aneuploid cell lines. These subclonal cell lines showed changes in growth pattern and morphology, as well as a karyotype drift concomitant with the overexpression of genes commonly involved in malignant transformation (c-MYC, EGFR, HIF-1alpha and LDH-A). Moreover, when one of these cell lines (RenG2) was injected into nude mice, it showed the ability to induce tumors. This cell line revealed no microsatellite instability (MSI), which points to the expression of a functional MLH1 protein and an active mismatch repair (MMR) system. Therefore, the progression to malignancy of the BEAS-2B cells involved Cr(VI)-induced transformants that retained the ability to repair DNA damage, suggesting that genotoxicity underlies the ongoing carcinogenic process.

How do cognitive and axial motor signs correlate in Parkinson's disease? A 6-year prospective study.

Impairment of Parkinson's disease (PD) axial motor signs (AMS) has been described as a risk factor for dementia. Executive dysfunction is an important feature in recently proposed clinical diagnostic criteria for PD dementia. To clarify the relationship between AMS progression and executive cognitive performance, we conducted a 6-year prospective study in PD patients without AMS impairment at baseline. A hospital-based cohort of PD patients (n = 24) without dementia, in the initial motor stage (Hoehn-Yahr < or = 2), and matched controls (n = 20) were followed prospectively over a 6-year period. Neuropsychological tests were performed in both groups, and motor function (including AMS: speech, gait, postural instability) was evaluated in the PD group. The PD group had a significantly higher decline in neuropsychological test scores than did the controls. Most of the neuropsychological and motor decline occurred in the last 4 years. In UPDRS III, progression of AMS and especially speech were the most important motor variables related to dementia. There was a correlation between speech impairment progression and declines in MMSE (r = -0.598, p = 0.002), Clock Drawing (r = -0.671, p < 0.001), Semantic Verbal Fluency (r = -0.435, p = 0.034), Alternating Sequences (r = 0.497, p = 0.014), and Raven's Coloured Progressive Matrices (r = -0.735, p < 0.001). PD patients with higher speech impairment progression showed more rapid declines in some neuropsychological tests. Further studies are needed to clarify the different roles of speech, gait and postural instability on the initial phases of cognitive dysfunction.

Kinetics and dynamic evaluation of specific immunotherapy.

UNLABELLED: Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy. MATERIAL AND METHODS: We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy. RESULTS: The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic focalisations were present for all the patients, whereas bowel focalisations were only observed for the subcutaneous route of administration. Sublingual SIT did not induce axillary or intestinal inflammatory focalisations, even though the patients had swallowed the allergenic extract. The uptake coefficient in individualized areas corrected to the uptake coefficient background was also studied. CONCLUSIONS: For the subcutaneous route of administration, except for glutaraldehyde-modified allergen, the local inflammatory activity at the allergenic injection site was significantly higher in depth and was time dependent, maintaining activity even after complete disappearance of the erythema and/or wheal. These results express a prompt inflammatory involvement of the immune system with this allergenic therapy, which was unexpected until now. We also observed differences concerning allergic diseases, the type of allergenic extracts and routes of administration.

Superantigen immune stimulation activates epithelial STAT-1 and PI 3-K: PI 3-K regulation of permeability.

Signal transducers and activators of transcription (STATs) are critical intracellular signaling molecules for many cytokines. We compared the ability of T84 epithelial cells to activate STATs in response to cytokines [interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and tumor necrosis factor-alpha (10 ng/ml)] and conditioned medium from superantigen [Staphylococcus aureus enterotoxin B (SEB)]-activated peripheral blood mononuclear cells (PBMC) using electrophoretic mobility shift assays (EMSA). Of the cytokines tested, only IFN-gamma caused a STAT-1 response. Exposure to SEB-PBMC-conditioned medium resulted in STAT-1 or STAT-1/3 activation, and inclusion of anti-IFN-gamma antibodies in the conditioned medium abolished the STAT-1 signal. Cells treated with transcription factor decoys, DNA oligonucleotides bearing the STAT-1 recognition motif, and then SEB-PBMC-conditioned medium displayed a reduced STAT-1 signal on EMSA, yet this treatment did not prevent the drop in transepithelial resistance (measured in Ussing chambers) caused by SEB-PBMC-conditioned medium. In contrast, the phosphatidylinositol 3'-kinase (PI 3-K) inhibitor LY-294002 significantly reduced the drop in transepithelial resistance caused by SEB-PBMC-conditioned medium. Thus data are presented showing STAT-1 (+/-STAT-3) and PI 3-K activation in epithelial cells in response to immune mediators released by superantigen immune activation. Although the involvement of STAT-1/-3 in the control of barrier function remains a possibility, PI-3K has been identified as a regulator of T84 paracellular permeability.

Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway. Lack of evidence for STAT 6 involvement.

Interleukins 4 and 13 can affect their target cells by activation of signal transducer and activator of transcription 6 (STAT 6) or phosphatidylinositol 3-kinase (PI3K). We examined the signal transduction events involved in IL-4 and IL-13 regulation of epithelial paracellular permeability using T84 cells, a model human colonic epithelium. T84 cells treated with IL-4 or IL-13 displayed virtually identical dose- and time-dependent STAT 6 activation as assessed by electrophoretic mobility shift assay (EMSA) and decreases in transepithelial resistance (TER). STAT 6 DNA binding activity was maximal in nuclear extracts 30 min after exposure to IL-4 or IL-13, and TER was maximally reduced by 24 h post-treatment. Pretreatment of epithelia with transcription factor decoys (phosphorothioated DNA oligonucleotides containing the STAT 6 binding site) dramatically reduced STAT 6 activation as detected by EMSA, but did not attenuate the TER reduction by IL-4 or IL-13. In contrast, although the PI3K inhibitors wortmannin and LY294002 did not affect IL-4 or IL-13 STAT 6 activation, they significantly inhibited the ability of either cytokine to lower TER. Thus, we provide evidence for PI3K as the major proximal signaling event in IL-4 and IL-13 regulation of TER and speculate that pharmacological targeting of enterocytic PI3K activity may represent a means to manipulate epithelial permeability.

Dynamical features simulated by recurrent neural networks.

The evolution of two-dimensional neural network models with rank one connecting matrices and saturated linear transfer functions is dynamically equivalent to that of piecewise linear maps on an interval. It is shown that their iterative behavior ranges from being highly predictable, where almost every orbit accumulates to an attracting fixed point, to the existence of chaotic regions with cycles of arbitrarily large period.