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STUDY QUESTION: Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? SUMMARY ANSWER: As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. WHAT IS KNOWN ALREADY: Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months). STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%. PARTICIPANTS/MATERIALS, SETTING, METHODS: SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29-34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan. MAIN RESULTS AND THE ROLE OF CHANCE: Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20-48) versus IVF: 47 (25-61); P-value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P-value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. LIMITATIONS, REASONS FOR CAUTION: The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART. STUDY FUNDING/COMPETING INTEREST(S): This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)-co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Fertilização in vitro , Infertilidade , Gravidez , Criança , Feminino , Humanos , Fertilização in vitro/métodos , Estudos Prospectivos , Peso Fetal , Remodelação Ventricular , Infertilidade/etiologiaRESUMO
OBJECTIVE: In light of the role of immune cells in OA pathogenesis, the development of sophisticated animal models closely mimicking the immune dysregulation during the disease development and progression could be instrumental for the preclinical evaluation of novel treatments. Among these models, immunologically humanized mice may represent a relevant system, particularly for testing immune-interacting DMOADs or cell therapies before their transfer to the clinic. Our objective, therefore, was to develop an experimental model of OA by destabilization of the medial meniscus (DMM) in humanized mice. METHOD: Irradiated 5-week-old NOD/LtSz-scid IL2Rγnull (NSG) mice were humanized by intravenous injection of CD34+ human hematopoietic stem cells. The engraftment efficiency was evaluated by flow cytometry 17 weeks after the humanization procedure. Humanized and non-humanized NSG mice underwent DMM or sham surgery and OA development was assessed 1, 6, and 12 weeks after the surgery. RESULTS: 120 days after the humanization, human T and B lymphocytes, macrophages and NK cells, were present in the blood and spleen of the humanized NSG mice. The DMM surgery induced articular cartilage and meniscal alterations associated with an increase in OA and the meniscal score. Moreover, the surgery triggered an inflammatory response that was sustained at a low grade in the DMM group. CONCLUSIONS: Our study shows for the first time the feasibility of inducing OA by DMM in humanized mice. This novel OA model could constitute a useful tool to bridge the gap between the preclinical and clinical evaluation of immune interacting DMOADs and cell-based therapies.
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Cartilagem Articular , Osteoartrite , Animais , Cartilagem Articular/patologia , Modelos Animais de Doenças , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Camundongos , Camundongos Endogâmicos NOD , Osteoartrite/patologiaRESUMO
OBJECTIVE: We aimed to explore fetal cortical brain development by neurosonography in fetuses conceived by assisted reproductive technology (ART), including frozen and fresh embryo transfer (ET), compared with those conceived spontaneously (SC), and to investigate its association with infant neurobehavior at 12 months of age. METHODS: This was a prospective cohort study of 210 singleton pregnancies, including 70 SC pregnancies, 70 conceived by in-vitro fertilization (IVF) following frozen ET and 70 conceived by IVF after fresh ET. Fetal neurosonography was performed at 32 ± 2 gestational weeks to assess cortical development. Sulci depths were measured offline and normalized by biparietal diameter (BPD). Ages and Stages Questionnaires (ASQ) were completed postnatally, at 12 ± 1 months of corrected age. Neurosonographic findings were adjusted by regression analysis for maternal age, ethnicity, parity, fetal sex and fetal-weight centile and gestational age at scan, and ASQ scores were adjusted for maternal age, ethnicity, parity, educational level and employment status, gestational age at birth, breastfeeding, infant sex and infant age at the ASQ evaluation. RESULTS: Overall, in comparison to the SC fetuses, fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital sulci depth adjusted for BPD (mean ± SD: fresh ET, 12.5 ± 2.5 vs frozen ET, 13.4 ± 2.6 vs SC, 13.4 ± 2.6, P < 0.001), cingulate sulci depth adjusted for BPD (median (interquartile range (IQR)): fresh ET, 5.8 (4.2-7.4) vs frozen ET, 5.8 (4.1-7.5) vs SC, 6.5 (4.8-7.8), P = 0.001) and calcarine sulci depth adjusted for BPD (median (IQR): fresh ET, 13.5 (10.1-16.1) vs frozen ET, 14.5 (12.1-15.8) vs SC, 16.4 (14.3-17.9), P < 0.001), together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET than in the frozen ET group. ART infants showed lower ASQ scores as compared to SC infants, particularly in the fresh ET group (mean ± SD global ASQ Z-score: fresh ET, -0.3 ± 0.4 vs frozen ET, -0.2 ± 0.4 vs SC, 0 ± 0.4, P < 0.001). CONCLUSIONS: Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in those conceived following fresh ET. These findings support the existence of in-utero brain reorganization associated with ART and warrant follow-up studies to assess its long-term persistence. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Transferência Embrionária , Técnicas de Reprodução Assistida , Gravidez , Recém-Nascido , Lactente , Feminino , Humanos , Estudos Prospectivos , Fertilização in vitro , FertilizaçãoRESUMO
STUDY QUESTION: Do fetuses from frozen embryo transfer (FET) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from fresh embryo transfer (ET)? SUMMARY ANSWER: Fetuses from both fresh ET and FET present signs of fetal cardiac remodeling and suboptimal function, with more pronounced changes after fresh ET as compared to FET. WHAT IS KNOWN ALREADY: Our group and others have previously demonstrated that fetuses and children conceived by ARTs present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. Cardiac changes were already present in utero and persisted after birth. Most of the ART fetuses included in previous publications were from fresh ET. However, singletons from FET have different perinatal outcomes compared to those from fresh ET. There are no previous studies comparing cardiac morphology and function between fetuses following fresh and FET. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study of 300 singleton pregnancies recruited from 2017 to 2020, including 100 spontaneously conceived (SC) pregnancies, 100 fetuses conceived by IVF with FET, and 100 fetuses conceived by IVF with fresh ET. Fetal structural and functional echocardiography was performed in all pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnancies conceived by IVF were recruited from a single assisted reproduction center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation for FET, laboratory procedures, and embryo culture conditions. SC pregnancies from fertile couples were selected from the general population and matched to IVF pregnancies by maternal age. Epidemiological and perinatal outcomes were collected in all cases. Fetal echocardiography was performed at 28-33 weeks of pregnancy to assess cardiac structure and function in all pregnancies. All echocardiographic comparisons were adjusted by maternal age, nulliparity, birthweight centile, preeclampsia, and prematurity. MAIN RESULTS AND THE ROLE OF CHANCE: Parental age, ethnicity, body mass index and smoking were similar among the study groups. Median gestational age at echocardiography and estimated fetal weight were similar in all study groups. Both fresh ET and FET groups showed similar fetal echocardiographic changes, with more pronounced features in the fresh ET as compared to FET pregnancies. Fetuses conceived by IVF showed larger atria (right atria-to-heart ratio: fresh ET mean 18.1% (SD 3.2) vs FET 18.0% (3.9) vs SC 17.3% (3.2); linear tendency P-value <0.001), more globular ventricles (right ventricular sphericity index: fresh ET 1.62 (0.29) vs FET 1.61 (0.25) vs SC 1.68 (0.26); <0.001) and thicker myocardial walls (relative wall thickness: fresh ET 0.79 (0.21) vs FET 0.74 (0.22) vs SC 0.65 (0.25); <0.001) as compared to SC pregnancies. Both fresh ET and FET groups also had signs of suboptimal systolic and diastolic function, with reduced tricuspid annular systolic peak velocity (fresh ET 7.17 cm/s (1.22) vs FET 7.41 cm/s (1.19) vs SC 7.58 cm/s (1.32); <0.001) and increased left myocardial performance index (fresh ET 0.53 (0.08) vs FET 0.53 (0.08) vs SC 0.50 (0.09); <0.001) as compared to SC pregnancies. LIMITATIONS, REASONS FOR CAUTION: The cardiac changes reported here are subclinical, with most cardiovascular indexes lying within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease remains to be proven. The observed milder fetal cardiac features in FET fetuses cannot condition the choice of this technique and must be considered together with the global perinatal results related to these gestations. WIDER IMPLICATIONS OF THE FINDINGS: The identification of cardiac remodeling in fetuses conceived by IVF with fresh ET and FET represents an opportunity for early detection. Future studies are warranted to study the potential long-term consequences of these findings. STUDY FUNDING/COMPETING INTEREST(S): This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI17/00675, PI18/00073) integrated into the Plan Nacional de I + D+I and cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa', Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant n° 1531. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Transferência Embrionária , Remodelação Ventricular , Criança , Feminino , Fertilização , Fertilização in vitro , Feto , Humanos , Gravidez , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Intrathecal analgesia has increased over the past two decades in various indications: chronic refractory pain from cancerous or non-cancerous origins, spasticity. These different indications involve the use of different molecules alone or in combination such as morphine, ropivacaine, bupivacaine, fentanyl, sufentanil, clonidine, baclofen and ziconotide. Pump refills are prepared at the pharmacy under a laminar flow hood. An analytical control should be carried out before release of the preparation. A new method of analytical control by chromatography has been developed and validated according to the International Conference on Harmonization guideline in order to secure the production process.
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Anestesia Endotraqueal , Anestésicos/análise , Anestésicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Humanos , Espasticidade Muscular/tratamento farmacológico , Dor Intratável/tratamento farmacológico , Espectrofotometria UltravioletaRESUMO
Interleukin (IL)-36α, IL-36ß and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36ß and IL-38 mRNA, was induced and correlated with IL-1ß and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, ß, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1ß, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1ß and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68⺠macrophages, dendritic/Langerhans cells and CD79α⺠plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36ß and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.
Assuntos
Artrite Reumatoide/patologia , Doença de Crohn/patologia , Interleucina-1/biossíntese , Interleucinas/biossíntese , Psoríase/patologia , Aminoquinolinas , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/imunologia , Células CACO-2 , Linhagem Celular , Doença de Crohn/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Imiquimode , Inflamação/imunologia , Inflamação/patologia , Interleucina-1/genética , Interleucinas/genética , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Queratinócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Plasmócitos/metabolismo , Psoríase/imunologia , RNA Mensageiro/biossíntese , Pele/metabolismo , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo , Células Th17/imunologiaRESUMO
OBJECTIVE: To analyse the doctor-patient relationship from the patient's point of view and from the doctor's point of view. MATERIAL AND METHODS: Experience of a chairman of a chronic pelvic and perineal pain patient association (AFAP-NP) and experience of doctors specialized in chronic pelvic and perineal pain. RESULTS: Management of a patient with chronic pelvic and perineal pain requires knowledge and understanding of the patient's trajectory disease, the history of the disease and the patient's hopes and disappointments, and evaluation of the patient's personality and family, social and work environment. CONCLUSION: As pain is an emotional experience, the type of doctor-patient relationship determines the quality of subsequent management. A number of basic principles should be applied: believe the patient, avoid making the patient feel responsible for failure, avoid overestimating the secondary benefits, avoid making the patient passive and dependent, learn to reinterpret the patient's symptoms, ask "how" does the pain persist rather than "why", clearly define the patient's demand and adapt management to realistic and accessible objectives.
Assuntos
Dor Pélvica , Períneo , Relações Médico-Paciente , Doença Crônica , Humanos , Dor Pélvica/diagnóstico , Dor Pélvica/terapiaRESUMO
Previous studies have shown that the nicotine-derived N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces tracheal papillomas and lung carcinomas in Syrian golden hamsters. In this study, we showed that hamster tracheal and lung explants metabolize NNK by alpha-carbon hydroxylation, pyridine N-oxidation and carbonyl reduction. alpha-Methylene hydroxylation and methyl hydroxylation yield methylating and pyridyloxobutylating intermediates, respectively. Levels of binding of the pyridyloxobutyl moiety to explant proteins was 200 times lower than the total amount of metabolites formed by alpha-carbon hydroxylation and released in the culture medium. Viable and heat-treated lung explants were cultured with [CH3-3H]NNK or [5-3H]NNK. In viable explants, the rate of binding of the methyl group was 2-fold higher than the rate of binding of the pyridyloxobutyl moiety of NNK. Heat treatment reduced 54-fold the binding of [CH3-3H] NNK but only 5-fold the binding [5-3H]NNK. Tracheal explants were cultured with [5-3H]NNK (5.6 microM) and ellagic acid (EA, 10 microM), a naturally-occurring plant phenol. EA did not inhibit any of the three metabolic pathways nor the binding of the pyridyloxobutyl moiety to explant proteins. Lung explants were cultured with NNK (3.7 microM) and with or without EA (100 microM). EA inhibits alpha-carbon hydroxylation by 19% and the overall metabolism of NNK by 6%. Formation of 7-methylguanine and O6-methylguanine was observed in lung explants and the levels of both adducts were reduced by EA (100 microM). These results suggest that high concentrations of EA modulate the metabolism of NNK and that NNK does not necessarily require enzymatic activation to bind to protein.
Assuntos
Benzopiranos/farmacologia , Carcinógenos/metabolismo , Ácido Elágico/farmacologia , Pulmão/metabolismo , Nitrosaminas/metabolismo , Traqueia/metabolismo , Alquilação , Animais , Peso Corporal/efeitos dos fármacos , Cricetinae , Técnicas de Cultura , Temperatura Alta , Hidroxilação , Masculino , Mesocricetus , OxirreduçãoRESUMO
OBJECTIVES: To evaluate the relationships between airway subepithelial collagen deposition and epithelial desquamation with airflow obstruction and hyperresponsiveness in different types of asthma and other respiratory conditions such as chronic cough and allergic rhinitis. DESIGN AND PARTICIPANTS: We compared the histopathologic features observed on bronchial biopsy specimens obtained from 80 subjects: 38 with different types of asthma, 19 with chronic cough, 13 with allergic rhinitis, and 10 normal control subjects. Each subject had a questionnaire on respiratory symptoms and medication needs, measurements of expiratory flows and methacholine responsiveness, allergy skin prick tests, and a bronchoscopy with bronchial biopsies. None of the subjects studied used bronchial anti-inflammatory agents. RESULTS: Different degrees of bronchial subepithelial fibrosis were present in asthmatic subjects, the most intense being observed in occupational asthma; a subepithelial deposition of collagen was also found in subjects with allergic rhinitis, although it was less intense than in asthma and irregularly distributed under the basement membrane. On global analysis, we found a significant correlation between individual provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) and subepithelial fibrosis intensity (rs=-0.70, p<0.001). The degree of epithelial desquamation was correlated with that of subepithelial fibrosis (rs=0.36, p=0.02) in subjects with normal airway responsiveness, but it was not correlated with the PC20 (rs=0.10, p>0.05). Neither the degree of subepithelial fibrosis nor epithelial desquamation was correlated with the FEV1. CONCLUSION: These results suggest that structural airway changes such as subepithelial collagen deposition may be significant determinants or markers of a process that results in airway hyperresponsiveness.
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Asma/patologia , Brônquios/patologia , Hiper-Reatividade Brônquica/patologia , Broncoconstritores , Cloreto de Metacolina , Rinite Alérgica Perene/patologia , Adulto , Asma/diagnóstico , Asma/fisiopatologia , Biópsia , Hiper-Reatividade Brônquica/diagnóstico , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Estudos de Casos e Controles , Doença Crônica , Colágeno/metabolismo , Tosse/diagnóstico , Tosse/patologia , Tosse/fisiopatologia , Feminino , Fibrose , Humanos , Masculino , Doenças Profissionais/diagnóstico , Doenças Profissionais/patologia , Doenças Profissionais/fisiopatologia , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/fisiopatologiaAssuntos
Artérias/citologia , Células Epiteliais , Junções Intercelulares , Animais , Aorta/citologia , Aorta Abdominal/citologia , Artérias Carótidas/citologia , Vasos Coronários/citologia , Endotélio/citologia , Técnicas Histológicas , Artéria Ilíaca/citologia , Lantânio , Masculino , Microscopia Eletrônica , Ratos , Coloração e Rotulagem , UrânioRESUMO
We have reported morphological and functional features of cells isolated from human bronchial biopsies. Both epithelial and fibroblastic cells were isolated from the same biopsies using collagenase. A few models have been established to study normal bronchial response to various agents and to understand the mechanisms responsible for some disorders, such as asthma. We produced three-dimensional bronchial equivalents in culture, using human epithelial and fibroblastic cells. We previously showed that peripheral anchorage can prevent the dramatic collagen contraction in gels seeded with fibroblasts when properly adapted to the size and type of cultured tissues. Our bilayered bronchial constructs were anchored and cultured under submerged conditions and at the air-liquid interface. Three culture media were compared. Serum-free medium supplemented with retinoic acid (5 x 10(-8) M) was found to be the best for maintenance of bronchial cell properties in the reconstructed bronchial tissue. Immunohistological and ultrastructural analyses showed that these equivalents present good structural organization, allowing ciliogenesis to occur in culture. Moreover, human bronchial goblet cells could differentiate and secrete mucus with culture time. Laminin, a major constituent of the basement membrane and basal cells, was also detected at the mesenchymoepithelial interface. Such models will be useful for studying human bronchial properties in vitro.
Assuntos
Brônquios/citologia , Fibroblastos/fisiologia , Mucosa Respiratória/fisiologia , Engenharia Tecidual/métodos , Cílios/fisiologia , Meios de Cultura , Gelatinases , Humanos , Imuno-Histoquímica , Laminina/metabolismo , Microscopia Eletrônica de Varredura , Mucosa Respiratória/ultraestrutura , Tretinoína/fisiologiaRESUMO
Asthma treatment has moved from bronchodilator therapy to an emphasis on anti-inflammatory therapy. Airway inflammation is believed to induce airway hyper-responsiveness (AHR) through the release of mediators that increase the airway response to agonists. However, the exact contribution of airway inflammation in the physiology of airway hyper-responsiveness remains undefined. Structural modifications in airways resulting from inflammation may contribute to the development and persistence of AHR and the development of asthma. This paper reviews some of the main components of airway inflammation and structural changes in asthma, and discusses how these processes may interact to modify airway function and induce respiratory symptoms.
Assuntos
Asma/etiologia , Asma/patologia , Brônquios/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Resistência das Vias Respiratórias , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Citocinas/fisiologia , Epitélio/patologia , Fibrose/etiologia , Humanos , Inflamação/patologia , EsteroidesRESUMO
Congestive cardiomyopathies represent a group of diseases having in common an intrinsic abnormality of the myocardial contraction, of which the cause often remains unknown. In children, there is a more marked incidence during the first year of life. At the Cardiology Institute of Quebec, 25 patients have been diagnosed with a congestive cardiomyopathy since January 1967. The mortality remains high at 48 per cent, and the morbidity at 28 per cent. Thus, the chance of total survival at 16 years was 33 percent. The evaluation and the treatment of the cardiac function as well as the search for a specific etiology must be carried out because the etiological treatment is sometimes possible. Biopsy of the skeletal muscle as the study of fatty acids metabolism have become very important since the identification of a carnitine deficiency. On the other hand, biopsy of the endomyocardium remains the only means to make a pathological diagnosis. Since the treatment of persisting myocarditis is feasible, the histological diagnosis is a pre-requisite in children. So, in four patients with congestive cardiomyopathy, biopsy of the endocardium has enabled to demonstrate a chronic inflammation of the myocardium in one patient. In three other cases, two had non specific lesions on histological examination an one had an extensive fibro-elastosis. As the symptomatic treatment is often deceiving, an in-depth investigation is mandatory in a child suffering from a congestive cardiomyopathy in order to identify an etiology. Such an approach will enable to apply a specific treatment, to achieve a better understanding and perhaps modify its natural history.
Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Adolescente , Biópsia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Carnitina/deficiência , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Recém-Nascido , Miocárdio/patologia , Doenças Neuromusculares/diagnósticoRESUMO
OBJECTIVE: Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A(2) (TXA(2)), a potent vasoconstrictor, and prostacyclin (PGI(2)), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q(10) (CoQ(10)), and the production of vasoactive eicosanoids- PGI(2) and TXA(2)-potentially regulated by pro-oxidants and antioxidants in preeclampsia. METHODS: Therefore, the plasma levels of vitamin E, CoQ(10), TXA(2) and PGI(2) in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ(10) in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB(2) and 6-keto-PGF(1alpha), stable metabolites of TXA(2) and PGI(2) respectively, were measured by ELISA. RESULTS: The CoQ(10) oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ(10), corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF(1alpha)/TXB(2) ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ(10) in all pregnancies (p <0.023). CONCLUSION: The data indicated that CoQ(10) is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ(10) suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF(1alpha)/TXB(2) ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.
Assuntos
Hipertensão/fisiopatologia , Estresse Oxidativo , Pré-Eclâmpsia/fisiopatologia , Adulto , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Epoprostenol/sangue , Ácidos Graxos/sangue , Feminino , Humanos , Seleção de Pacientes , Pré-Eclâmpsia/sangue , Gravidez , Tromboxano A2/sangue , Ubiquinona/análogos & derivados , Ubiquinona/sangue , Vitamina E/sangueAssuntos
Citoesqueleto/patologia , Rejeição de Enxerto/patologia , Transplante de Coração/imunologia , Transplante de Coração/patologia , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4 , Infecções Tumorais por Vírus/complicações , Núcleo Celular/patologia , Núcleo Celular/ultraestrutura , Citoesqueleto/ultraestrutura , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/virologia , Coração/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma/etiologia , Linfoma/imunologia , Linfoma/patologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Microscopia Eletrônica , Miocárdio/ultraestrutura , Receptores de Complemento 3d/análise , Receptores de IgE/análise , Receptores Virais/análise , Vacúolos/patologia , Vacúolos/ultraestruturaRESUMO
Report of a histochemical and ultrastructural study of the Hamasaki-Wesenberg Bodies in ganglionic sarcoidosis. These peculiar bodies have variable form and size and are located in the ganglionic sinuses as free elements or in the histiocytes; they are found most often in cases with sarcoidosis but are not specific of this disease. The results of this study suggest that their origin is probably lysosomial and that their nature is not unlike that of ceroid or lipofuscinic pigments. The exact signification of the presence of these bodies in the lymph nodes would need deeper investigation.
Assuntos
Corpos de Inclusão , Linfonodos , Doenças Linfáticas/patologia , Pigmentos Biológicos/metabolismo , Sarcoidose/patologia , Humanos , Linfonodos/patologia , Linfonodos/ultraestrutura , Doenças Linfáticas/metabolismo , Sarcoidose/metabolismoRESUMO
The effects of acute cigarette smoking and bilateral ovariectomy on the thickness of rat aortic cell coat (Con A) were investigated. Ovariectomized rats showed a significant increase in the thickness of the cell coat. When cigarette smoking was combined with ovariectomy the thickness of the reaction product was similar to controls. Cigarette smoke without ovariectomy resulted in a decreased thickness, but these changes were not significant.
Assuntos
Aorta Torácica/ultraestrutura , Castração , Membrana Celular/ultraestrutura , Nicotiana , Plantas Tóxicas , Fumaça/efeitos adversos , Animais , Concanavalina A , Endotélio/ultraestrutura , Feminino , Microscopia Eletrônica , Lectinas de Plantas , Ratos , Ratos EndogâmicosRESUMO
In this study we have compared myocardial lesions induced by catecholamines and coronary occlusion and reperfusion injuries in rats. Although microcirculatory factors were found to play an important role in catecholamine-induced cardiac muscle cell injury, alterations in sarcolemmal membrane permeability suggest a direct cardiotoxic effect. Cardiac muscle cells damaged irreversibly by ischemia reveal sarcomeres in extreme relaxation and mitochondria with floccular densities; cardiac muscle cells that die following reperfusion exhibit contraction band formation and mitochondria with calcium phosphate deposits. The ultrastructural appearance of reperfused ischemic cardiac muscle cells was similar to that observed following administration of catecholamines. These morphological similarities suggest a common causal pathway for stress-induced and ischemic heart diseases.
Assuntos
Catecolaminas/farmacologia , Doença das Coronárias/patologia , Miocárdio/patologia , Animais , Permeabilidade da Membrana Celular/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/metabolismo , Doença das Coronárias/terapia , Peroxidase do Rábano Silvestre/metabolismo , Isoproterenol/farmacologia , Infarto do Miocárdio/terapia , Necrose/induzido quimicamente , Ratos , Sarcolema/efeitos dos fármacosRESUMO
An ultrastructural and histochemical study of the subendocardial lesion in carcinoid heart disease showed six different cell types within a myxoid matrix. The matrix, composed of a mucopolysaccharidic ground substance, collagen, and reticluin fibers, contained stem cells, four types of fusiform cells (fibrocytes, fibroblasts, myofibroblasts, and smooth muscle cells), and intermediary cell type. Our observations suggest that the humoral mediators of the carcinoid syndrome may induce the differentiation of a subendocardial stem cell into contractile elements.