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Arctic coasts are transition zones influenced by terrestrial, marine, and cryospheric factors. Due to the degradation of the cryosphere exacerbated by climate change, many segments of Arctic coasts are characterized by severe erosions and thus resulting in many social-economic consequences. To assess the imminent coastal risks and increasing organic carbon fluxes released from Arctic erosional coasts, continuous monitoring of shoreline movement is necessary. Conventional studies employ spaceborne multi-spectral optical images to detect ample Arctic coasts' dynamics; nonetheless, the frequent cloud cover and Arctic haze limit the number of usable images. Thence, most studies merely utilize a few image pairs to estimate long-term rate changes, which deter statistically meaningful trend analysis and are likely biased by intra-annual variations. This study employs cross-mission synthetic aperture radar (SAR) images that are cloud-penetrating and weather-independent to depict 32-year spatiotemporal changes of Drew Point Coast along the Alaskan Beaufort Sea. To efficiently and robustly extract shorelines, a non-manual intervention-required and cross-SAR sensor applicable approach is proposed. Based on the automatically delineated time series shoreline positions, each coastal segment's position-time records are modeled with a statistic-based coastal dynamics classification scheme that enables constructing non-linear trends of inter-decadal recession rates. Results reveal that 83.7 % of the coast exhibits continuous erosion during 1992-2023. Dynamically, 48.6 % of coast demonstrates polynomial change patterns with an erosive rate higher than -6 m/yr. Remarkably, 22.5 % of the coast has been statistically significantly accelerating. For instance, the erosional rate nearly double (93.8 %) between Drew Point and McLeod Point, while between Lonely and Pitt Point, the most erosive segment in the study coast, the retreating rate increases 285.57 % from -5.92 to -22.81 m/yr. These findings exemplify the high heterogeneity of Arctic coastal changes and highlight the opportunities of using spaceborne SAR data to empower the management and conservation of Arctic coasts.
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More than 80% of sandy beaches in Taiwan have been experiencing a severe recession, although the sediment discharge of rivers in Taiwan is significantly higher than the world average producing almost 2% of global fluvial sediment discharge. This contradiction is primarily due to the widespread constructions of reservoirs and intensive anthropogenic activities in coastal regions. In addition, coasts are particularly vulnerable to hazards due to climate change, such as sea-level rise, as they are located at the transition zone of terrestrial and marine environments. Along with the fact that Taiwan is an island and is one of the most climate-vulnerable regions globally, coastal management and sustainability are nationally critical topics, especially considering the ongoing reformation and legislation of Taiwan's coastal conservation laws. As stated in the Sustainable Development Goals (SDGs) goal 14, accurate and continuous shoreline positions information is essential for coastal conservation. However, by reviewing previous global studies and projects commissioned by the Taiwanese government aiming at monitoring shoreline changes, they usually exhibit several limitations, such as limited band selections or conservative band ratio-derived water indices, relying on either manual digitization or simple thresholding methods, focusing on either artificial or smoothly shaped coasts, and using images acquired at considerably different tidal height levels. Therefore, in the present study, a subpixel shoreline extraction approach based on a sustainable cross-generation dataset and a robust edge detection algorithm is proposed. This approach is exemplified by the Zengwun River Estuary located in southwestern Taiwan-Taiwan's most critical coastal preservation region. By quantitatively analyzing the resultant time-series shoreline positions from 1999 to 2021, several hotspots of shoreline recession have been identified: an extreme erosional rate up to -69.4 m year-1 is revealed in the northern sand bank; while the offshore sand bar demonstrates an overall landward retreat rate of -35.4 ± 1.24 m year-1.
Assuntos
Monitoramento Ambiental , Estuários , Mudança Climática , Monitoramento Ambiental/métodos , Areia , TaiwanRESUMO
OBJECTIVES: To study the link between metabolic syndrome (MetS), endothelial injury, and atherosclerosis in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients without a history of arterial thrombosis were screened for atherosclerosis at the carotid and coronary arteries by B-mode ultrasound [intima-media thickness (IMT)] and multidetector computed tomography (MDCT) scan (Agatston calcium scores), respectively. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule (sVCAM)-1, P-selectin, and soluble thrombomodulin (sTM) were assayed. Patients were stratified according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria for MetS, using the Asian criteria for abdominal obesity. Risk factors for atherosclerosis were studied. RESULTS: Of the 123 SLE patients (93% women; age 47.9+/-11 years; SLE duration 10.9+/-7.0 years) studied, 20 (16.3%) had MetS. The prevalence of MetS in the SLE patients was significantly higher than in 492 age- and sex-matched healthy controls (9.6%; p=0.03). Coronary calcification and abnormal carotid IMT were detected in 38 (31%) and 72 (59%) of SLE patients, respectively. Patients with MetS had a significantly higher Agatston score (69.5+/-95 vs. 16.4+/-57; p=0.03) and a numerically higher carotid IMT (p=0.43) than those without. In a logistic regression model, the MetS [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.01-9.59, p=0.049] was associated with coronary atherosclerosis after adjustment for age and other risk factors. In addition, patients with MetS had significantly higher levels of hsCRP (p=0.002), homocysteine (p=0.03), and sTM (p=0.01). CONCLUSIONS: The MetS is more prevalent in SLE patients than the general population and is associated with endothelial injury and coronary atherosclerosis. More aggressive control of risk factors is justified in these patients.
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Aterosclerose/epidemiologia , Endotélio Vascular/patologia , Lúpus Eritematoso Sistêmico/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Adulto , Distribuição por Idade , Aterosclerose/diagnóstico por imagem , Biomarcadores/sangue , Análise Química do Sangue , Proteína C-Reativa/metabolismo , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estudos de Casos e Controles , Comorbidade , Intervalos de Confiança , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Citocinas/metabolismo , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Probabilidade , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fator de Necrose Tumoral alfa/metabolismo , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Túnica Média/diagnóstico por imagem , Túnica Média/patologia , UltrassonografiaRESUMO
Similar to many southern and southeast Asian regions, the mobilisation of arsenic (As) from sediments has driven a widespread contamination problem for groundwater resources in the Cambodian Mekong Delta. For the first time, the seasonal changes in As concentrations and potential links to groundwater pumping for irrigation in shallow aquifers of the Cambodian Mekong Delta are investigated. Using environmental tracers (δ18O, δ2H, 3H, major/trace ions and rare earth elements) the natural and pumping-induced changes in hydrogeological processes are identified. Three conceptual models are proposed: Model 1, where there is limited local recharge or low recharge rates (3H mean residence time > 60 years) and groundwater has a large range in As concentrations (0.2 to 393.8 µg/L). In this semi-confined aquifer, only one of the six groundwater sites has As concentrations that increase (by 10.9 µg/L) potentially due to groundwater pumping and resultant mixing with high-As and low (Pr/Sm)NASC groundwater. However, data on groundwater extraction volumes is required to verify the link with irrigation practices. Model 2, where groundwater is recharged by evaporated surface waters (fractionated δ18O and δ2H). There are moderate As concentrations (64.1-106.1 µg/L) but no significant seasonal changes even though the recharging waters have relatively greater organic carbon contents during the dry season (reduced Ce/Ce*anomaly). Finally model 3, where groundwater is significantly recharged by wet season rainfall (~50% from δ18O data). There is a minor increase in As concentrations with recharge (by 6. µg/L). These combined results highlight an aquifer system in the irrigated region of the Cambodian Mekong Delta where As concentrations are largely impacted by natural rather than irrigation processes. Seasonal-scale recharge processes control As processes where the aquifer is not confined by shallow clay layers, and where the aquifer is semi-confined As concentrations largely reflect longer-term natural processes.
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A recently identified interleukin (IL)-17-producing T-helper (Th) lymphocyte subset, which comprises Th17 cells producing hallmark cytokines IL-17A, IL-17F and IL-22, is involved in chronic inflammatory diseases. Elevated gene and protein expressions of IL-17 are manifested in allergic asthma. We further characterized the activation of Th17 cells in asthmatic patients. Peripheral blood mononuclear cells (PBMC) were purified from 31 asthmatic patients and 20 sex- and age-matched control subjects. The number of IL-17A secreting cells in peripheral blood was enumerated by enzyme-linked immunosorbent spot assay. Cell surface expression of Th17-related chemokine receptor CCR6, and plasma level of IL-17A, IL-17F and IL-22, and ex vivo production of IL-17A and IL-22 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The number of peripheral Th17 lymphocytes, expression of CCR6 on Th cells, and ex vivo IL-23, anti-CD3 and anti-CD28 induced production of IL-22 by PBMC were significantly elevated in asthmatic patients compared with control subjects (all p < 0.01). This clinical study further confirmed increased number of peripheral Th17 lymphocytes and cell surface expression of CCR6 receptors on Th cells in asthmatic patients. Pro-inflammatory cytokine IL-23 can exacerbate disease severity by activating pathogenic Th17 lymphocytes to release downstream inflammatory cytokine IL-22 in asthma.
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Asma/sangue , Interleucina-17/metabolismo , Leucócitos Mononucleares/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Asma/metabolismo , Asma/patologia , Antígenos CD28/imunologia , Complexo CD3/imunologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/sangue , Interleucina-23/farmacologia , Interleucinas/sangue , Interleucinas/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Receptores CCR6/metabolismo , Linfócitos T Auxiliares-Indutores/citologia , Adulto Jovem , Interleucina 22RESUMO
BACKGROUND: We postulate that hypercytokinemia plays a role in immunopathogenesis of severe human influenza. METHODS: We prospectively studied 39 consecutive patients who were hospitalized with severe influenza A virus infection. On laboratory confirmation of the diagnosis, paired acute-phase (obtained at hospital admission) and convalescent-phase (obtained >10 days after hospital admission) plasma samples were collected for assay of 11 cytokines and chemokines (interleukin [IL] 1 beta; IL-6; IL-10; IL-12p70; tumor necrosis factor alpha; IL-8; monokine induced by interferon [IFN]-gamma; IFN-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation, normal T cell-expressed and secreted; and IFN-gamma) using cytometric bead-array analysis and enzyme-linked immunosorbent assay. Simultaneously, virus concentration in the acute-phase nasopharyngeal aspirate was determined using real-time quantitative reverse-transcriptase polymerase chain reaction. Intracellular signaling molecules regulating lymphocyte activation, phospho-p38 mitogen-activated protein kinase and phospho-extracellular signal-regulated protein kinase in CD4+ and CD8+ T lymphocytes were studied in the acute-phase samples using flow cytometric analysis and were compared with results for samples from healthy control subjects. RESULTS: Statistically significant increases in plasma IL-6 (3.7-fold increase), IL-8 (2.6-fold increase), IFN-induced protein 10 (4.9-fold increase), and monokine induced by IFN-gamma (2.3-fold increase) concentrations were detected during acute illness (P < .01 for all, by Wilcoxon signed-rank test); the highest concentrations were observed on symptom days 3 and 4. Corresponding plasma cytokine and chemokine concentrations and nasopharyngeal viral loads showed statistically significant correlations (rho = 0.41, 0.49, 0.54, and 0.46, respectively; P < or = .01). Phospho-p38 mitogen-activated protein kinase expression in CD4+ lymphocytes was increased, correlating with cytokine concentrations (e.g., for IFN-induced protein 10, rho = 0.78; P < .01); phospho-extracellular signal-regulated protein kinase was suppressed. Advanced age and comorbidity were associated with aberrant IL-6, IL-8, and monokine induced by IFN-gamma responses (P < .05, by Mann-Whitney U test). An elevated IL-6 concentration was independently associated with prolonged hospitalization (hospitalization for >5 days; P = .02), adjusted for age, comorbidity, and virus load. CONCLUSIONS: Hypercytokinemia (of proinflammatory and T helper 1 cytokines) is detected in severe influenza, correlating with clinical illness and virus concentration. Hyperactivation of phospho-p38 mitogen-activated protein kinase (in T helper cells) is possibly involved. Early viral suppression may attenuate these potentially deleterious cytokine responses.
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Citocinas/sangue , Vírus da Influenza A/genética , Influenza Humana/sangue , Influenza Humana/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adolescente , Adulto , Quimiocina CXCL9/sangue , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Influenza Humana/patologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Fosforilação , Estudos Prospectivos , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/sangueRESUMO
Monoclonal antibody against TNF-alpha such as infliximab has shown clinical efficacy in controlling the inflammatory signs and symptoms of rheumatoid arthritis (RA), but the detailed immunotherapeutic mechanism is not fully understood. We investigated 19 patients with active RA who were treated with infliximab (3 mg/kg) at weeks 0, 2, 6 and 14. Peripheral blood was obtained from the patients at weeks 0 and 14 and cultured with mitogens phytohaemagglutinin (PHA) and lipopolysaccharide (LPS). The concentrations of cytokines and soluble adhesion molecules (sICAM-1, sICAM-3, sE-selectin, sP-selectin, sVCAM-1 and sPECAM-1) in supernatant fluids or plasma were measured by flow cytometry and ELISA. After infliximab treatment, the absolute and percentage increases in release of inflammatory cytokine TNF-alpha and potent neutrophil chemoattractant IL-8 upon PHA and LPS activation were significantly decreased when compared to those of before treatment (all P<0.01). The increased releases of IL-6, IL-1beta, IL-18 and IL-12 upon mitogen activation were similar before and after infliximab treatment (all P>0.05). Plasma concentrations of these cytokines and soluble adhesion molecules did not differ significantly before and after infliximab treatment. Our study suggests that the reduction in synovial inflammation may be due to the decreased production of TNF-alpha and IL-8, and hence the number of neutrophils and other pro-inflammatory leukocytes infiltrating into the inflamed sites.
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Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Interleucina-8/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Artrite Reumatoide/imunologia , Citocinas/biossíntese , Feminino , Humanos , Infliximab , Interleucina-8/biossíntese , Interleucina-8/sangue , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Early detection of an acute rejection episode is an important problem in monitoring transplant patients. Erythropoietin (EPO) production is diminished in patients suffering from chronic renal insufficiency or acute rejection. Therefore, a decrease of reticulocyte counts and of young reticulocytes might indicate the emergence of an acute rejection episode. This pilot study examined the value of reticulocyte parameters as indicators of acute rejection episodes. PATIENTS AND METHODS: Reticulocyte parameters were examined in 25 renal transplant patients. Initial immunosuppressants therapy was based on a combination of methylprednisolone, mycophenolatmofetil, cyclosporine and antithymocyte globulin or basiliximab, CellCept, cyclosporine, and ATG or Simulect. During the first 3 weeks after the procedure, blood samples were collected three times per week. Complete blood counts were performed on XE-2100 analyzers (Sysmex). Acute rejection was biopsy-proven. RESULTS: Acute rejection episodes were not accompanied by significantly altered reticulocyte parameters. During the first weeks, the reticulocyte count or the immature fraction, respectively, did not differ between patients with delayed versus immediate onset of renal function: reticulocyte count 1.70 +/- 1.06% vs 1.58 +/- 1.10% and ratio of immature (high fluorescent) reticulocytes 22.8 +/- 7.9% vs 17.6 +/- 9.4%). CONCLUSION: Reticulocyte counts and determination of the immature reticulocyte fraction were not significantly altered by an acute rejection episode. Various influences modulate the release of EPO and reaction of erythropoiesis upon an EPO stimulus.
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Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Contagem de Reticulócitos , Adulto , Idoso , Creatinina/sangue , Eritropoetina/sangue , Feminino , Rejeição de Enxerto/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/sangueRESUMO
From examination of inherited patterns of ovulation rate in sheep, several breeds have been identified with point mutations in two growth factor genes (BMP15 and GDF9) and a related receptor (ALK6) that are expressed in oocytes. Five different point mutations have been identified in the BMP15 gene, one in GDF9 and one in ALK6. Animals heterozygous for these mutations or heterozygous for two of these mutations or homozygous for the ALK6 mutation have higher ovulation rates (i.e. +0.6-10) than their wild-type contemporaries. Animals homozygous for the BMP15 or GDF9 mutations are sterile due to arrested follicular development from the primary stage of growth. The BMP15 and GDF9 mutations are thought to result in reduced levels of mature protein or altered binding to cell-surface receptors. In sheep, GDF9 mRNA is present in germ cells before and after ovarian follicular formation as well as throughout follicular growth, whereas BMP15 mRNA is found in oocytes only from the primary stage of growth. Also ALK6 together with related cell-surface receptors such as ALK5 and BMPRII mRNA are present in oocytes at most, if not all, stages of follicular growth. Both GDF9 and BMP15 proteins are present in follicular fluid indicating that they are secreted products. Immunisation of sheep with GDF9 or BMP15 peptides shows that both growth factors are essential for follicular development, ovulation and/or corpus luteum formation. In animals with the ALK6 mutation, ovarian follicles undergo precocious maturation leading to three to seven follicles ovulating at smaller diameters without any increase above wild-types in the ovarian secretions of steroid or inhibin. One important consequence of the ALK6 mutation appears to be a decreased ability of some BMPs to inhibit differentiation of follicular cells. Current findings in sheep suggest that BMP15, GDF9 and ALK6 are targets for new methods of fertility regulation in some mammals.
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Peptídeos e Proteínas de Sinalização Intercelular/genética , Oócitos/metabolismo , Ovulação/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento/genética , Ovinos/genética , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Feminino , Expressão Gênica , Fator 9 de Diferenciação de Crescimento , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Mutação Puntual , Proteínas Serina-Treonina Quinases/imunologia , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento/imunologiaRESUMO
In view of the reported inhibitory effect of angiotensin II on cortisol secretion in human subjects, the effect of local angiotensin infusions on steroid secretion maintained by ACTH was examined by using sheep with cervical autotransplanted adrenal glands. During sustained submaximal stimulation by exogenous ACTH (40--80 microunit/min), the addition of local infusions of angiotensin II (1.6--160.0 ng/min) caused increased aldosterone and smaller increments in cortisol secretion in most experients. There was no evidence of inhibition of cortisol secretion by angiotensin. When similar experiments were undertaken during maximum stimulation by ACTH (16.6 mU/min), increments in aldosterone, but not in cortisol secretion, were observed. These studies exclude an acute inhibitory effect of angiotensin on cortisol biosynthesis, at least in ovine adrenal glands, during stimulation by ACTH.
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Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Angiotensina II/farmacologia , Hidrocortisona/metabolismo , Aldosterona/metabolismo , Animais , OvinosRESUMO
Previous work suggests that aldosterone is modulated by dopamine, which exerts an inhibitory effect at the level of the adrenal cortex. This study reports the effect of dopamine on aldosterone secretion in conscious sheep with cervical adrenal transplants in whom endogenous ACTH secretion was suppressed by dexamethasone. In control experiments (n = 7) local adrenal infusions of angiotensin II (AII) (1.6 ng/min for 120 min) increased aldosterone secretion to peak levels (47.8 +/- 6.8 ng/min. mean +/- SEM) at 20 min, after which secretion fell to stable levels (20-28 ng/min) at 60-120 min. On separate days, sheep were restudied (n = 5) during systemic dopamine infusions (4 microgram/kg . min for 90 min), commencing 30 min before AII stimulation. There was no significant difference, either in the pattern or the sensitivity of the aldosterone response to AII, with dopamine infusions. Large intraadrenal infusions of dopamine (10 microgram/min) also failed to alter the aldosterone response to AII. The possibility that aldosterone was already under maximum tonic inhibition by dopamine was studied in four additional experiments using the dopamine blocking drug, metoclopramide. Although the systemic (iv) administration of metoclopramide increased aldosterone in both intact and transplanted sheep, local infusions of metoclopramide (0.5-15 microgram/min intraarterially) had no consistent effect on the aldosterone response to AII, and the addition of dopamine during metoclopramide infusions also had no effect. These results indicate that local (adrenal) dopaminergic mechanisms play little or no part in the regulation of aldosterone secretion in the sheep. The mechanism whereby aldosterone secretion is increased by systemic metoclopramide remains to be explained.
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Aldosterona/metabolismo , Dopamina/farmacologia , Glândulas Suprarrenais/transplante , Angiotensina II/sangue , Angiotensina II/farmacologia , Animais , Dexametasona/farmacologia , Feminino , Hidrocortisona/sangue , Metoclopramida/farmacologia , Prolactina/sangue , Ovinos , Fatores de TempoRESUMO
The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.
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Glycyrrhiza , Hidrocortisona/urina , Plantas Medicinais , Adenoma/sangue , Hormônio Adrenocorticotrópico/sangue , Adulto , Feminino , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Valores de ReferênciaRESUMO
Potassium and angiotensin II are major regulators of aldosterone secretion. To assess which of these stimuli is the more potent, we measured aldosterone, potassium, and angiotensin II responses to the oral converting enzyme inhibitor captopril in five patients with resistant congestive heart failure during digoxin and furosemide maintenance therapy. In spite of a positive cumulative potassium balance and a clear-cut rise in plasma potassium, aldosterone levels in plasma and urine declined in parallel with levels of angiotensin II. When captopril treatment was later withdrawn in three patients, angiotensin II and aldosterone levels increased in parallel, while plasma potassium remained steady. The results show that under these study conditions, angiotensin II is more potent than potassium in regulating aldosterone in patients with heart failure.
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Aldosterona/sangue , Angiotensina II/sangue , Captopril/uso terapêutico , Insuficiência Cardíaca/sangue , Potássio/sangue , Prolina/análogos & derivados , Idoso , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
The methylotrophic yeast, Pichia pastoris, has been used to co-express recombinant genes formed by fusion of the mating factor-alpha (MFalpha) leader and ovine follicle stimulating hormone (oFSH) alpha and beta subunit coding sequences. Pichia strains carrying single copies of the two fusion genes secreted recombinant oFSH (roFSH) to concentrations of approximately 51.0 ng/ml and 17.5 ng/ml, measured by RIA or in vitro bioassay respectively, whereas a strain with two copies of the alpha and one copy of the beta subunit fusion genes secreted roFSH to concentrations of 61 ng/ml (RIA) and 22 ng/ml (bioassay). It appears that the Pichia-derived roFSH had about one-third the in vitro bioactivity of native oFSH or, alternatively, only one-third of the roFSH is bioactive. Measurements of secreted roFSH alpha and beta subunit concentrations indicated less than 10% of alpha and 25-33% of beta subunits were stably dimerized. The receptor binding properties of the roFSH resemble those of native oFSH. In summary this paper reports the production, by P. pastoris, of a heterodimeric glycoprotein hormone (roFSH) that has in vitro biological activity.
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Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Pichia/genética , Animais , Sequência de Bases , Clonagem Molecular , Primers do DNA/genética , Dimerização , Hormônio Foliculoestimulante/química , Subunidade beta do Hormônio Folículoestimulante , Expressão Gênica , Subunidade alfa de Hormônios Glicoproteicos/química , Subunidade alfa de Hormônios Glicoproteicos/genética , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Plasmídeos/genética , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ovinos , Transformação GenéticaRESUMO
The pituitary-derived glycoprotein hormone FSH plays a central role in controlling vertebrate gonadal function. In female mammals the maturation of ovarian follicles is critically dependent upon stimulation by FSH. Moreover, injection of exogenous FSH is used extensively to stimulate increased numbers of follicles to ovulate. Structurally FSH is a heterodimeric glycoprotein composed of two non-covalently associated polypeptide subunits. The tertiary structures of both the alpha- and beta-subunits are constrained by intramolecular disulphide bonds and are post-translationally modified with two N-linked carbohydrate moieties, the structure of which appears to modulate in vivo biological activity. Here we report the expression of ovine FSH (oFSH) as a biologically active single-chain polypeptide using the methylotrophic yeast Pichia pastoris. Sequences encoding the mature oFSH alpha- and beta-proteins were fused to form a gene encoding a fusion protein with the C-terminus of the beta-chain joined to the N-terminus of the alpha-chain, with the chains separated by a two amino acid linker sequence. This fusion gene was itself fused to two alternative Pichia leader sequences (mating factor alpha and acid phosphatase) and transformed into the Pichia strains GS115 and SMD1168. The recombinant fusion protein (oFSHbetaalpha) was expressed at approximately 0.1 microg/ml in 'shake-flask' cultures. The Pichia-expressed tethered protein was biologically active in an in vitro bioassay, had a molecular mass of 28 kDa, as determined by SDS-PAGE, and bound the bovine FSH receptor with a binding profile similar to that of native oFSH.
Assuntos
Subunidade beta do Hormônio Folículoestimulante/biossíntese , Subunidade alfa de Hormônios Glicoproteicos/biossíntese , Pichia/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Fusão Gênica Artificial , Bovinos , Códon , Feminino , Subunidade beta do Hormônio Folículoestimulante/genética , Subunidade beta do Hormônio Folículoestimulante/metabolismo , Engenharia Genética , Subunidade alfa de Hormônios Glicoproteicos/genética , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Pichia/genética , Receptores do FSH/metabolismo , Proteínas Recombinantes de Fusão/genética , OvinosRESUMO
Granulosa cells from ovarian follicles (greater than or equal to 1 mm diameter) in Booroola ewes which are homozygous (FF) or heterozygous (F+) for the F gene have previously been shown to produce significantly more cAMP in response to FSH or LH than those from similar sized follicles in ewes without the F gene (++). The aim of these studies was to test whether these F gene-specific differences arose because of differences in cAMP-phosphodiesterase (cAMP-PDE) activity. In the first study using 1 mumol cAMP/l as substrate, no F gene-specific effects were noted in cAMP-PDE activity in granulosa cells from small (1-2.5 mm diameter, n = 4 per genotype) or large (greater than or equal to 3 mm diameter, n = 4 per genotype) follicles from FF, F+ or ++ ewes, despite F gene-specific effects in FSH (1 microgram/ml)- and LH (0.1 microgram/ml)-induced cAMP accumulation in these same cell preparations. The overall mean levels of cAMP-PDE across all genotypes in cells from small and large follicles were 0.47 +/- 0.04 (S.E.M., n = 12) and 0.28 +/- 0.03 pmol cAMP/10(6) cells per min respectively; the mean PDE activity in cells from small follicles was significantly (P less than 0.05) higher compared with that in cells from large follicles. In a second study, granulosa cells from each genotype were pooled over all follicle sizes (greater than or equal to 1 mm diameter, one pool per genotype) and the rates of cAMP hydrolysis tested over a range of substrate concentrations (0-16 mumol/l) but no gene-specific differences with respect to the Michaelis constant and maximum velocity were noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Genes , Células da Granulosa/enzimologia , Ovinos/genética , Animais , AMP Cíclico/metabolismo , Feminino , Fertilidade , Hormônio Foliculoestimulante/farmacologia , Genótipo , Células da Granulosa/efeitos dos fármacos , Hormônio Luteinizante/farmacologia , Folículo Ovariano/anatomia & histologiaRESUMO
This study in ewes examined the effects on ovarian function of a pulsatile regimen of ovine FSH (NIADDK-oFSH-17) administered over a 24- to 28-day period beginning on day 1 of the oestrous cycle (day 0 = oestrus). The FSH (1.66 micrograms or 5.00 micrograms) was administered i.v. over a 1-min interval once every hour throughout the treatment period. In other ewes ovine LH (NIDDK-oLH-23) was administered (10 micrograms once every 2 h) for 24-28 days together with oFSH (1.66 micrograms/h). Compared with untreated controls (n = 19 ewes), FSH alone at both doses (n = 10 ewes/dose) as well as the FSH + LH treatment (n = 10) led to significant increases in the plasma concentrations of FSH (P < 0.01), ovarian weight (P < 0.05) and ovulation rate (P < 0.01) but there was no change in the mean weight of individual corpora lutea (CL). Exogenous FSH at the high but not the low dose alone or with LH stimulated a significant overall increase in plasma inhibin concentrations (P < 0.05). The geometric mean (and 95% confidence limits) ovulation rates in the high FSH (i.e. 5.00 micrograms/h), low FSH (i.e. 1.66 micrograms/h), low FSH + LH, and control treatment groups were 15.3 (9.3, 24.8), 3.7 (2.1, 6.0), 3.7 (2.5, 5.8) and 1.4 (1.2, 1.7) respectively. The FSH or FSH + LH treatments did not alter the total numbers of antral follicles (> or = 1 mm diameter). However, the high but not the low FSH or low FSH + LH treatment led to significant increases in the mean numbers of large follicles (i.e. > 4.5 mm diameter; P < 0.01) and a higher proportion of non-atretic antral follicles. Highly significant linear relationships were found between the mean plasma concentrations of FSH or inhibin and the ovulation rate (FSH: r = 0.74, P < 0.0001; inhibin: r = 0.93, P < 0.0001). Highly significant linear relationships were also found between the plasma concentrations of FSH or inhibin and the number of large follicles (i.e. > 4.5 mm diameter; FSH, r = 0.78, P < 0.0001; inhibin, r = 0.80, P < 0.0001) and between the plasma concentrations of inhibin and the number of granulosa cells in large follicles (r = 0.78, P < 0.0001). After the high FSH but not the low FSH treatment there were significant increases in both FSH- and LH-induced responsiveness in granulosa cells with respect to cyclic AMP synthesis in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Corpo Lúteo/efeitos dos fármacos , Hormônio Foliculoestimulante/farmacologia , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ovinos/fisiologia , Animais , Corpo Lúteo/fisiologia , Feminino , Hormônio Foliculoestimulante/sangue , Inibinas/sangue , Hormônio Luteinizante/sangue , Hormônio Luteinizante/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/fisiologia , Ovário/anatomia & histologiaRESUMO
The aim of this study was to examine the effect of the FecBB fecundity gene on plasma concentrations and pituitary content of growth hormone (GH) in sheep. No differences were found between homozygous carriers (BB) and non carriers (++) of the FecBB gene with regard to pituitary GH contents in both ovariectomized and intact ewes. However, ovariectomized ewes had higher levels of pituitary GH than intact ewes (P < 0.01). There were no differences between FecBB genotypes with respect to plasma concentrations of GH in 6-year-old ovariectomized ewes bled every 10 min for 12 h or in ram lambs bled weekly during their first year of life. GH levels in the rams decreased until week 27, increased to a peak at week 31 then decreased before increasing again at week 43. Mean plasma GH concentrations in the ewe lambs bled weekly for a year decreased until week 19 then remained at approximately this level for the remainder of the year. Mean GH plasma concentrations in the ram lambs were higher than in the ewe lambs (P < 0.001). Ewe lambs that were homozygous for the FecBB gene had lower body weights (P < 0.05) and had higher levels of GH (P < 0.01) than non carrier ewe lambs during their first year. Before the average age of first behavioural oestrus (36 weeks) GH levels in the ewe lambs were negatively correlated with body weights (r = -0.69, P < 0.001, n = 22). When body weight was included as a covariate in analysis of variance the genotype difference in ewe lamb plasma GH concentrations was no longer significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fertilidade/genética , Hormônio do Crescimento/metabolismo , Hipófise/metabolismo , Ovinos/genética , Análise de Variância , Animais , Animais Recém-Nascidos , Peso Corporal , Feminino , Hormônio do Crescimento/sangue , Homozigoto , Masculino , Ovariectomia , Ovinos/metabolismoRESUMO
The plasma concentrations of LH and prolactin and various parameters of ovarian function were examined in cows on known days of the oestrous cycle during May and June (autumn and winter) and during October (spring). Luteinizing hormone peak frequency and plasma prolactin concentrations were significantly higher in October than during the May-June period (LH, P less than 0.05; prolactin, P less than 0.01). The mean diameters of large healthy follicles (greater than or equal to 8 mm diameter) and the dominant oestrogen-secreting follicles were significantly larger (P less than 0.01 for both follicle types) and each follicle contained more granulosa cells (both P less than 0.01) in May-June than in October. The LH responsiveness of theca interna with respect to androstenedione production and the levels of aromatase activity in granulosa cells did not differ with time of year. The corpora lutea were heavier (P less than 0.05) and secreted more progesterone (P less than 0.01) in May-June than in October. It is concluded that seasonal differences in ovarian activity exist in cows and that these differences are probably the consequence of seasonal differences in gonadotrophin secretion.
Assuntos
Bovinos/fisiologia , Ovário/fisiologia , Estações do Ano , Androstenodiona/biossíntese , Animais , Aromatase/metabolismo , Corpo Lúteo/fisiologia , Estradiol/metabolismo , Estro , Feminino , Células da Granulosa/fisiologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/farmacologia , Folículo Ovariano/fisiologia , Gravidez , Prolactina/sangue , Células Tecais/metabolismoRESUMO
The aim of the present study was to examine the interrelationships between the luteinizing hormone (LH) receptor, the LH-induced changes in adenosine cyclic 3', 5'-monophosphate (cAMP) and steroid synthesis in theca interna tissue of large antral follicles (greater than or equal to 8 mm diameter) from oestrous cycling cows. Three distinct types of theca interna were identified (types I, II and III), all of which contained an LH receptor: type I was capable of secreting increased amounts of cAMP dehydroepiandrosterone, androstenedione and testosterone when exposed to LH; type II was capable of secreting increased amounts of cAMP and progesterone but not the androgens when exposed to LH; type III was incapable of cAMP or steroid synthesis when exposed to LH. Follicles with type I thecae contained: a full complement of granulosa cells; high intrafollicular concentrations of oestradiol; and granulosa cells with a high capacity to metabolise testosterone to oestradiol. These follicles were considered to be non-atretic structures. Follicles with types III thecae contained: fewer granulosa cells; low intrafollicular concentrations of oestradiol; and granulosa cells with a low capacity to metabolise testosterone to oestradiol. Moreover, follicles with type III thecae contained the highest concentrations of progesterone and the lowest concentrations of androstenedione and testosterone. These follicles were considered to be severely atretic structures. Follicles with type II thecae contained granulosa cell populations and progesterone, and androgen concentrations which were intermediate between those with thecae of types I and III. These follicles were considered to be at an intermediate stage of atresia.(ABSTRACT TRUNCATED AT 250 WORDS)