15,022 research outputs found

    Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection

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    Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease

    Domains and prominence in nasal harmonization of Maxakalí loanwords

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    We examine the patterns of loanword adaptation in Maxakalí, a Macro-Jê language of Brazil, in importing loans from Brazilian Portuguese, with respect to the introduction of nasality and nasal harmony, based on a corpus of 18 speakers. Employing MaxEnt modeling of quantitative trends enabled the comparison and analysis of certain recurrent trends, even if not exceptionless, and the potentially additive effects of their interaction. The results reveal that nasal harmonization, modeled as set of markedness constraints, is greatly enforced within syllable rimes, and strongly enforced within syllables, but shows little role for syllable-to-syllable harmony, demonstrating that harmonization is preferred within tighter prosodic domains. Word-initial consonants always retain their nasality or orality from Portuguese, and stressed vowels always preserve their nasality. These latter effects uphold the role of prominent positions in maintaining contrasts within loanword phonology. The overall patterns of loanword harmonization find convergence with certain characteristics within Maxakalí phonology itself

    Reproductive Performance of Dairy Cows Affected by Endometritis, Pododermatitis and Mastitis

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    The effects of endometritis, pododermatitis and clinical mastitis on the conception rate and calving-conception interval of multiparous and primiparous cows after fixed-time artificial insemination (FTAI) were evaluated. Clinical endometritis was diagnosed by ultrasonography 20-40 days postpartum upon observation of fluid in the uterine lumen. Cows with clinical endometritis were treated intramuscularly with 2 mg/kg ceftiofur hydrochloride over three consecutive days. Forty-five days after delivery, multiparous and primiparous cows with normal uteri according to ultrasonography were selected for the study, filed and inseminated by FTAI. To identify animals with hoof problems and clinical mastitis and to define their respective groups, the cows were observed daily during morning and nightly milking for up to 60 days after FTAI, and animals with hoof lesions were treated. Animals with clinical mastitis were treated with intramammary infusion containing 88 mg cefquinome sulphate every 12 h after milking for four days. The conception rate of multiparous cows with clinical endometritis at 30 and 60 days after FTAI was negatively affected compared with that of healthy cows with pododermatitis. However, clinical endometritis did not influence the primiparous category, whereas pododermatitis and clinical mastitis did not influence the conception rate of any category at 30 and 60 days after FTAI. Differences were not observed between primiparous or multiparous cows in the calving-conception interval. Keywords: Lactation, Pregnancy, Health, Fertilit

    Copd Phenotypes On Computed Tomography And Its Correlation With Selected Lung Function Variables In Severe Patients

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    Computed tomography (CT) phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD) patients, but its clinical relevance and its relationship with functional features are not clarified. Volumetric capnography (VC) uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume. The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath. Objective: To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables. Subjects and methods: Sixty-five patients with COPD Gold III-IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC). The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP) or airway disease (AWD) phenotype. EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables. Results: Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients. Structural findings of airways had no significant correlation with spirometric variables. Air trapping and EMP were strongly correlated with VC variables, but in opposite directions. There was some overlap between the EMP and AWD groups, but EMP patients had signicantly lower body mass index, worse obstruction, and shorter walked distance on 6MWT. Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3. Increases in Slp3 characterize heterogeneous involvement of the distal air spaces, as in AWD. Conclusion: Visual assessment and phenotyping of CT in COPD patients is feasible and may help identify functional and clinically different subsets of patients. VC may provide useful information about the heterogeneous involvement of lung structures in COPD.1150351

    Localisation in focal epilepsy: a practical guide

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    The semiology of epileptic seizures reflects activation, or dysfunction, of areas of brain (often termed the symptomatogenic zone) as a seizure begins and evolves. Specific semiologies in focal epilepsies provide an insight into the location of the seizure onset zone, which is particularly important for presurgical epilepsy assessment. The correct diagnosis of paroxysmal events also depends on the clinician being familiar with the spectrum of semiologies. Here, we summarise the current literature on localisation in focal epilepsies using illustrative cases and discussing possible pitfalls in localisation

    Extending the applicability of the dose addition model to the assessment of chemical mixtures of partial agonists by using a novel toxic unit extrapolation method

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    This article has been made available through the Brunel Open Access Publishing Fund.Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past. © 2014 Scholze et al

    The Effect 0f Warm-up on Tethered Front Crawl Swimming Forces

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    This study was conducted to determine the effect of warm-up on high-intensity front crawl tethered swimming and thus to better understand possible variations in the force exerted by the swimmers. Ten male national level swimmers (mean ± SD; age 15.3 ± 0.95 years old, height: 1.73 ± 5.2 m, body mass: 64.3 ± 7.8 kg, Fat mass 8.31 ± 3.1 kg) participated in this study. After a typical competition warm-up, the subjects performed a 30 s tethered swimming all-out effort in front crawl swimming technique. The same test was repeated in the day after but performed without warming up. Capillary blood lactate concentration was assessed before and after the swimming test and the Borg ratings of perceived exertion scale was used. Without a previous warm-up, the mean ± SD values of maximum and mean forces were 299.62 ± 77.56 N and 91.65 ± 14.70 N, respectively. These values were different (p<0.05) from the values obtained with warm-up (351.33 ± 81.85 N and 103.97 ± 19.11 N). Differences were also observed when regarding to the forces relative to body mass. However, the values of lactate net concentrations after the test performed with and without warm-up were not different (6.27 ± 2.36 mmol·l(-1) and 6.18 ± 2.353 mmol·l (-1)) and the same occurs with the values of ratings of perceived exertion (15.90 ± 2.42 and 15.60 ± 2.27). These results suggest an improvement of the maximum and mean force of the swimmer on the tethered swimming due to previous warm-up.UBI/FCSH/Santander/2010info:eu-repo/semantics/publishedVersio

    Septic Shock Following Hysteroscopy. A Case Report

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    Introduction: Minimally invasive gynecological surgery such as hysteroscopy has a small risk of complications. These include uterine perforation (with or without adjacent pelvic organ lesion), bleeding and infection, and are more common in the presence of risk factors such as smoking, history of pelvic inflammatory disease (PID) and endometriosis. Case presentation: A patient submitted to a diagnostic hysteroscopy with no immediate complications was admitted five days later to the emergency department in septic shock. The diagnosis of ruptured tubal abscess was made, requiring emergency laparotomy with sub-total hysterectomy and bilateral adnexectomy. Despite multiple organ failure requiring admission to the intensive care unit, the patient made a full recovery. Conclusion: Ascending infection can be a life-threatening complication of hysteroscopy, even in the absence of previously known risk factors.info:eu-repo/semantics/publishedVersio

    Finasteride 5 mg/day Treatment of Patterned Hair Loss in Normo-androgenetic Postmenopausal Women

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    BACKGROUND: There is no consensus on the standard treatment options for female pattern androgenetic alopecia (AGA). Efficacy of finasteride in women is controversial. The purpose of this study was to evaluate the clinical efficacy and safety of 5 mg/day oral finasteride in normoandrogenic postmenopausal woman. MATERIALS AND METHODS: A total of 40 normoandrogenic postmenopausal women with AGA was enrolled in this study. They were treated with oral finasteride 5 mg/day for 18 months. Efficacy was evaluated by patient's satisfaction and global photograph assessment. All the 40 patients completed 18 months of finasteride treatment schedule. RESULTS: After 6 months, 22 patients referred significant improvement, 12 moderate improvement, and 6 no improvement. Regarding to global photo assessment, 8 patients showed no improvement, 16 showed moderate improvement and 16 showed significant improvements at the 6(th) month. A slight improvement was observed over time from 6 to 12 and 18 months observation. Maintained libido reduction was referred by four patients and liver enzymes increase was observed in one patient. Older patients were more prone to worse response. DISCUSSION: Finasteride 5 mg/day is effective and safe for the treatment of female AGA in postmenopausal women in the absence of clinical or laboratory signs of hyper-androgenism

    Validating Regulatory Sensory Processing Disorders Using the Sensory Profile and Child Behavior Checklist (CBCL 1 –5)

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    The objective was to validate Regulatory Sensory Processing Disorders’ criteria (DC:0-3R, 2005) using empirical data on the presence and severity of sensory modulation deficits and specific psychiatric symptoms in clinical samples. Sixty toddlers who attended a child mental health unit were diagnosed by a clinical team. The following two groups were created: toddlers with RSPD(N = 14) and those with ‘‘other diagnoses in Axis I/II of the DC:0-3R00(OD3R) (N = 46). Independently of the clinical process, parents completed the Infant Toddler Sensory Profile (as a checklist for sensory symptoms) and the Achenbach Behavior Checklist for ages 1/2–5 (CBCL 1/2–5). The scores from the two groups were compared. The results showed the following for the RSPD group: a higher number of affected sensory areas and patterns than in the OD3R group; a higher percentage of sensory deficits in specific sensory categories; and a higher severity of behavioral symptoms such as withdrawal, inattention, other externalizing problems and pervasive developmental problems in CBCL 1/2–5. The results confirmed our hypotheses by indicating a higher severity of sensory symptoms and identifying specific behavioral problems in children with RSPD. The results revealed convergent validity between the instruments and the diagnostic criteria for RSPD and supported the validity of RSPD as a unique diagnosis. The findings also suggested the importance of identifying sensory modulation deficits in order to develop an early intervention to enhance the sensory capacities of children who do not fully satisfy the criteria for some DSM-IV-TR disorders
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