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The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension., QC 20220214

In vitro toxicological experiments were performed on an endothelial cell line exposed to different doses of spherical nanoparticles of cadmium and/or of lead sulfides with mean diameter 37 ± 5 nm and 24 ± 4 nm, respectively. Toxic effects were estimated by Luminescent Cell Viability Assay, endothelin-1 concentration and cell size determination. Some dose-response relationships were typically monotonic (well approximated with hyperbolic function) while others were bi- or even 3-phasic and could be described within the expanded hormesis paradigm. The combined toxicity type variated depending on the effect it was assessed by. © The Author(s) 2021.

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m3 during 5 days for 4 h a day in a nose-only setup. A control group of rats were sham-exposed in parallel under similar conditions. Even this short-time exposure of a relatively low level was associated with nanoparticles retention demonstrable by transmission electron microscopy in the lungs and the olfactory brain. Some impairments were found in the organism’s status in the exposed group, some of which might be considered lead-specific toxicological outcomes (in particular, increase in reticulocytes proportion, in δ-aminolevulinic acid (δ-ALA) urine excretion, and the arterial hypertension’s development). © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: Accurate prediction of disease progression and therapeutic response in interstitial lung disease (ILD) is lacking. Validation of candidate serum biomarkers remains limited by small, single-centre studies without longitudinal disease measures. We assessed the diagnostic role of 28 biomarkers in two large, multicentre cohorts of Australian idiopathic pulmonary fibrosis (IPF) and scleroderma-ILD (SSc-ILD) patients with prospective longitudinal data and linked sera. Method(s): The serum concentration of 28 biomarkers was evaluated using bead-based multiplex assays (SP-D, MMP-1/-3/-7/-12, periostin, CXCL13, CCL2, IL-6/-8, CXCL4/-10/-12, TGF-beta, Ca15.3, Endothelin 1, VEGF, Amphiregulin, TIMP1, CCL18, ICAM, VCAM, E-selectin) and ELISA (KL-6, fibulin-1, LOXL2). IPF and SSc patients were identified from the Australian IPF Registry and Scleroderma Cohort Study, including prospective, longitudinal clinical and outcome data and linked serum biobanks. Sera was also obtained from non-smoking healthy controls. Result(s): 640 patients (mean age 60 +/- 13.7 years, 33% male, 52% ever smokers), including 172 IPF, 168 SSc, 270 SSc-ILD patients and 30 healthy controls were analysed. IPF patients were older (mean 70 +/- 18 years) and more male predominant (70% male). SSc-ILD patients were less likely to be ever smokers (44%). FVC did not differ between groups (mean 2.68 +/- 0.80L, 76 +/- 12%pred). DLCO was lower in IPF patients versus SSc and SSc-ILD (mean 38, 64 and 58% respectively; P <0.001) and SSc-ILD compared with SSc (P = 0.003). Conclusion(s): We identified a panel of serum proteins able distinguish IPF and SSc-ILD from non-ILD patients; between ILD subtypes; and SSc with and without ILD. Further analysis is required to determine the relationship of biomarkers with disease severity and outcomes.

Background Mirror syndrome (Ballantyne's syndrome) is a rare condition recognised in the context of non-immune and immune fetal hydrops with the presence of 'triple oedema' - a hydropic fetus, alongside marked maternal and placental oedema - hallmarking the maternal-fetal mirror. The mother may also develop proteinuria and hypertension, thereby simulating a clinical picture of preeclampsia; however, unlike pre-eclampsia, mirror syndrome is characterised by maternal haemodilution alongside fetal hydrops and polyhydramnios. The exact pathophysiology of mirror syndrome is not known, however that of pre-eclampsia is widely acknowledged to have genesis in abnormal placentation leading to hypoxia, placental oxidative stress and release of factors causing endothelial activation and vasoconstriction. Frequently implicated factors in this pathway include angiogenic factors such as the VEGF receptor sFlt, activin and follistatin, along with 8-isoprostane, endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF). Since mirror syndrome resembles a 'preeclampsia phenotype', we test the hypothesis that its clinical features are mediated by the same circulating factors as those in preeclampsia. Case We report the case of a 29 year-old at 26 + 2 weeks that underwent successful fetoscopic laser photocoagulation for Stage IV TTTS. Between days 4-5 post-procedure, the patient became increasingly hypertensive and proteinuric. Follow-up ultrasound was performed paradoxically showing new-onset ascites in the donor twin. On day 7, the patient became increasingly tachycardic, dyspnoeic and hypoxic. Blood indices showed: Hb 7.8 g/dL, Hct 0.22 L/L, albumin 16, CRP 56 and pO2 64 mmHg on room air. Chest X-ray confirmed pulmonary oedema. A diagnosis of mirror syndrome was made and the twins delivered by caesarean. Placental histopathology showed oedematous villi confined to the donor twin territory, pathognomonic of mirror syndrome. Concurrent to the clini

Background Mirror syndrome (Ballantyne's syndrome) is a rare condition recognised in the context of non-immune and immune fetal hydrops with the presence of 'triple oedema' - a hydropic fetus, alongside marked maternal and placental oedema - hallmarking the maternal-fetal mirror. The mother may also develop proteinuria and hypertension, thereby simulating a clinical picture of preeclampsia; however, unlike pre-eclampsia, mirror syndrome is characterised by maternal haemodilution alongside fetal hydrops and polyhydramnios. The exact pathophysiology of mirror syndrome is not known, however that of pre-eclampsia is widely acknowledged to have genesis in abnormal placentation leading to hypoxia, placental oxidative stress and release of factors causing endothelial activation and vasoconstriction. Frequently implicated factors in this pathway include angiogenic factors such as the VEGF receptor sFlt, activin and follistatin, along with 8-isoprostane, endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF). Since mirror syndrome resembles a 'preeclampsia phenotype', we test the hypothesis that its clinical features are mediated by the same circulating factors as those in preeclampsia. Case We report the case of a 29 year-old at 26 + 2 weeks that underwent successful fetoscopic laser photocoagulation for Stage IV TTTS. Between days 4-5 post-procedure, the patient became increasingly hypertensive and proteinuric. Follow-up ultrasound was performed paradoxically showing new-onset ascites in the donor twin. On day 7, the patient became increasingly tachycardic, dyspnoeic and hypoxic. Blood indices showed: Hb 7.8 g/dL, Hct 0.22 L/L, albumin 16, CRP 56 and pO2 64 mmHg on room air. Chest X-ray confirmed pulmonary oedema. A diagnosis of mirror syndrome was made and the twins delivered by caesarean. Placental histopathology showed oedematous villi confined to the donor twin territory, pathognomonic of mirror syndrome. Concurrent to the clini

The endothelin axis is a group of signaling molecules and their receptors that have been implicated in vascularization of cancers, with their expression being observed to change in different cancer types. In this research, we examined the expression of endothelin 1 and endothelin receptor A at the protein and messenger RNA (mRNA) levels in 123 papillary thyroid carcinomas and 40 matched lymph nodes with metastatic papillary thyroid carcinomas. We found altered endothelin axis mRNA expression in several clinicopathologic parameters with increased endothelin 1 expression in thyroid papillary carcinoma showing stromal calcification, cancers in men, and primary cancers with lymph node metastases. Increased endothelin receptor A mRNA expression was noted in the larger cancers. There is a significant correlation between expression of endothelin receptor A and endothelin 1 in papillary thyroid carcinoma. Both endothelin receptor A and endothelin 1 mRNA expressions were significantly higher in metastatic carcinoma in the lymph node than in primary thyroid cancer. The metastatic carcinoma in the lymph node had increased expression compared with matched primary thyroid carcinoma. Expressions of endothelin 1 and endothelin receptor A were also documented as being high at the protein level. Our results indicate that in thyroid cancer, endothelin 1 and endothelin receptor A are associated with growth in advanced stages and lymph node metastases, likely through known angiogenic linkages. Targeting the endothelin axis may be useful in planning angiogenesis therapy for thyroid cancer.

Endothelin-1 (ET-1) ist ein gefä?aktives Peptid, welches zusätzlich verschiedenste nicht kardiovaskuläre physiologische und pathophysiologische Effekte besitzt. So wurde z.B. beschrieben, dass ET-1 in der Brustdrüse während der Schwangerschaft und Stillzeit exprimiert wird. Zusätzlich zu den bekannten Nährstoffen und Wachstumsfaktoren konnte auch ET-1 in der Muttermilch nachgewiesen werden, was auf eine physiologische Rolle von ET-1 für die Laktation und den säugenden Nachwuchs hinweist. In der vorliegenden Arbeit sollte die Funktion von ET-1 in der Brustdrüsenentwicklung mit Hilfe von ET-1 transgenen Mäusen aufgeklärt werden. Die eingesetzten transgenen Tiere überexprimieren humanes ET-1 mit den entsprechenden 5''- und 3'' regulatorischen Sequenzen. Mit Hilfe dieser Strategie sollen die ET-1 spezifischen Funktionen während der Brustdrüsenentwicklung untersucht werden. Transgenes ET-1 wurde während der Tragzeit und Stillzeit in der Brustdrüse detektiert. Die Ergebnisse zeigten, dass säugende Neugeborene der ET-1 transgenen Mäuse eine geringere Gewichtszunahme und eine erhöhte Mortalität aufwiesen, welches auf einen Laktationsdefekt hinweist. Die histologische Untersuchung der Brustdrüse während der Tragzeit ergab eine reduzierte Milchkanalausbildung, kollabierte und nicht expandierende Alveoli, vermehrte Adipozytenausbildung und fortbestehende zytoplasmatische Lipidtropfen (CLDs). Zusätzlich war die Expression des Milchproteins WAP reprimiert. Interessanterweise wurde diese Repression nicht durch STAT5, einem beschriebenem Regulator der Milchproteinexpression und Alveolarexpansion, vermittelt, da dessen Aktivität unverändert war. Als Konsequenz dieses Laktationsdefekts konnte eine verfrühte Rückbildung der Brustdrüse festgestellt werden. Diese ging mit einer erhöhten Expression von STAT3 einher. Interessanterweise wies der bekannte Aktivator von STAT3, LIF, ebenfalls eine gesteigerte Aktivität auf, sowohl während der Tragzeit als auch während der Laktation. Zusätzli, Endothelin-1 (ET-1) is a potent vasoactive peptide having wide physiological effects on vascular homeostasis and on a variety of pathophysiological processes unrelated to cardiovascular system. It has been noted that ET-1 is expressed in mammary glands during pregnancy and lactation periods. Furthermore, ET-1 is secreted into milk, suggesting additional physiological roles in the lactating mother and in the suckling neonate. Hence, the present study was proposed to elucidate the possible functional roles of ET-1 in mammary gland development employing ET-1 transgenic mice. ET-1 transgenic mice had been generated by using a human genomic ET-1 construct containing 5´ and 3´ regulatory sequences. This transgenic construction strategy grants to analyse the specific functions of ET-1 in normal mammary gland physiology. The transgene expression was found in mammary gland during pregnancy and lactation. ET-1 transgenic mice exhibited a lactational incompetence with reduced weight gain and increased mortality of their newborns, as a result of a secretory defect. In virtue of this defect, ET-1 transgenic mammary glands histologically revealed a reduced ductal outgrowth, collapsed alveoli with a reduced expansion capacity, increased adipocyte accumulation, and persistence of cystoplasmic lipid droplets (CLDs) during lactation. In addition, the expression of the milk protein, WAP, was found to be constantly suppressed in ET-1 mammary glands although the activity of STAT5, which is known to be a regulator of the expression of milk proteins and alveolar expansion, was found to be normal. Furthermore, as a consequence of the secretory defect, ET-1 transgenic mammary glands exhibited focal precocious involution during early stages of lactation along with an increased activity of STAT3. Consistently, the known activator of STAT3, LIF, was strongly upregulated during lactation and pregnancy. Besides the secretory defect of ET-1 transgenic mammary glands, histological analysis reveale

Endothelin-1 (ET-1) ist ein gefä?aktives Peptid, welches zusätzlich verschiedenste nicht kardiovaskuläre physiologische und pathophysiologische Effekte besitzt. So wurde z.B. beschrieben, dass ET-1 in der Brustdrüse während der Schwangerschaft und Stillzeit exprimiert wird. Zusätzlich zu den bekannten Nährstoffen und Wachstumsfaktoren konnte auch ET-1 in der Muttermilch nachgewiesen werden, was auf eine physiologische Rolle von ET-1 für die Laktation und den säugenden Nachwuchs hinweist. In der vorliegenden Arbeit sollte die Funktion von ET-1 in der Brustdrüsenentwicklung mit Hilfe von ET-1 transgenen Mäusen aufgeklärt werden. Die eingesetzten transgenen Tiere überexprimieren humanes ET-1 mit den entsprechenden 5''- und 3'' regulatorischen Sequenzen. Mit Hilfe dieser Strategie sollen die ET-1 spezifischen Funktionen während der Brustdrüsenentwicklung untersucht werden. Transgenes ET-1 wurde während der Tragzeit und Stillzeit in der Brustdrüse detektiert. Die Ergebnisse zeigten, dass säugende Neugeborene der ET-1 transgenen Mäuse eine geringere Gewichtszunahme und eine erhöhte Mortalität aufwiesen, welches auf einen Laktationsdefekt hinweist. Die histologische Untersuchung der Brustdrüse während der Tragzeit ergab eine reduzierte Milchkanalausbildung, kollabierte und nicht expandierende Alveoli, vermehrte Adipozytenausbildung und fortbestehende zytoplasmatische Lipidtropfen (CLDs). Zusätzlich war die Expression des Milchproteins WAP reprimiert. Interessanterweise wurde diese Repression nicht durch STAT5, einem beschriebenem Regulator der Milchproteinexpression und Alveolarexpansion, vermittelt, da dessen Aktivität unverändert war. Als Konsequenz dieses Laktationsdefekts konnte eine verfrühte Rückbildung der Brustdrüse festgestellt werden. Diese ging mit einer erhöhten Expression von STAT3 einher. Interessanterweise wies der bekannte Aktivator von STAT3, LIF, ebenfalls eine gesteigerte Aktivität auf, sowohl während der Tragzeit als auch während der Laktation. Zusätzli, Endothelin-1 (ET-1) is a potent vasoactive peptide having wide physiological effects on vascular homeostasis and on a variety of pathophysiological processes unrelated to cardiovascular system. It has been noted that ET-1 is expressed in mammary glands during pregnancy and lactation periods. Furthermore, ET-1 is secreted into milk, suggesting additional physiological roles in the lactating mother and in the suckling neonate. Hence, the present study was proposed to elucidate the possible functional roles of ET-1 in mammary gland development employing ET-1 transgenic mice. ET-1 transgenic mice had been generated by using a human genomic ET-1 construct containing 5´ and 3´ regulatory sequences. This transgenic construction strategy grants to analyse the specific functions of ET-1 in normal mammary gland physiology. The transgene expression was found in mammary gland during pregnancy and lactation. ET-1 transgenic mice exhibited a lactational incompetence with reduced weight gain and increased mortality of their newborns, as a result of a secretory defect. In virtue of this defect, ET-1 transgenic mammary glands histologically revealed a reduced ductal outgrowth, collapsed alveoli with a reduced expansion capacity, increased adipocyte accumulation, and persistence of cystoplasmic lipid droplets (CLDs) during lactation. In addition, the expression of the milk protein, WAP, was found to be constantly suppressed in ET-1 mammary glands although the activity of STAT5, which is known to be a regulator of the expression of milk proteins and alveolar expansion, was found to be normal. Furthermore, as a consequence of the secretory defect, ET-1 transgenic mammary glands exhibited focal precocious involution during early stages of lactation along with an increased activity of STAT3. Consistently, the known activator of STAT3, LIF, was strongly upregulated during lactation and pregnancy. Besides the secretory defect of ET-1 transgenic mammary glands, histological analysis reveale

It is known in vertebrates that endothelin-1 (ET-1) plays a key role ill morphogenesis whose expression level greatly influences the development of craniofacial malformations. In the Present study, the complete cDNA fragment encoding a precursor of endothelin-1, the preproendothelin-1 (PPET1), was cloned by RACE-PCR from European sea bass. The cDNA encoded a 199 amino acid polypeptide that was composed of the "mature" and "big" ET-1. Relative ET-1 expression levels were investigated in European sea bass larvae fed microparticulate diets containing the standard amount (0.08 g retinol/kg diet: group N) or all excess of retinoic acid which induces skeletal malformations (0.5 g retinol/kg diet: group RA). Real-time reverse transcriptor polymerase chain reaction analysis revealed that PPET1 mRNA levels were sensitively reduced in the RA group during early development (days 10 and 15 post hatching). Regulation of ET-1 gene expression in larvae fed the teratogenic level of vitamin A confirmed the involvement of ET-1 in the molecular mechanism involved in craniofacial deformities. These results suggest that the expression level of ET-1 may be used as a precocious molecular marker to predict malformations during European sea bass development. (c) 2008 Elsevier B.V. All rights reserved.

It is known in vertebrates that endothelin-1 (ET-1) plays a key role ill morphogenesis whose expression level greatly influences the development of craniofacial malformations. In the Present study, the complete cDNA fragment encoding a precursor of endothelin-1, the preproendothelin-1 (PPET1), was cloned by RACE-PCR from European sea bass. The cDNA encoded a 199 amino acid polypeptide that was composed of the "mature" and "big" ET-1. Relative ET-1 expression levels were investigated in European sea bass larvae fed microparticulate diets containing the standard amount (0.08 g retinol/kg diet: group N) or all excess of retinoic acid which induces skeletal malformations (0.5 g retinol/kg diet: group RA). Real-time reverse transcriptor polymerase chain reaction analysis revealed that PPET1 mRNA levels were sensitively reduced in the RA group during early development (days 10 and 15 post hatching). Regulation of ET-1 gene expression in larvae fed the teratogenic level of vitamin A confirmed the involvement of ET-1 in the molecular mechanism involved in craniofacial deformities. These results suggest that the expression level of ET-1 may be used as a precocious molecular marker to predict malformations during European sea bass development. (c) 2008 Elsevier B.V. All rights reserved.

It is known in vertebrates that endothelin-1 (ET-1) plays a key role ill morphogenesis whose expression level greatly influences the development of craniofacial malformations. In the Present study, the complete cDNA fragment encoding a precursor of endothelin-1, the preproendothelin-1 (PPET1), was cloned by RACE-PCR from European sea bass. The cDNA encoded a 199 amino acid polypeptide that was composed of the "mature" and "big" ET-1. Relative ET-1 expression levels were investigated in European sea bass larvae fed microparticulate diets containing the standard amount (0.08 g retinol/kg diet: group N) or all excess of retinoic acid which induces skeletal malformations (0.5 g retinol/kg diet: group RA). Real-time reverse transcriptor polymerase chain reaction analysis revealed that PPET1 mRNA levels were sensitively reduced in the RA group during early development (days 10 and 15 post hatching). Regulation of ET-1 gene expression in larvae fed the teratogenic level of vitamin A confirmed the involvement of ET-1 in the molecular mechanism involved in craniofacial deformities. These results suggest that the expression level of ET-1 may be used as a precocious molecular marker to predict malformations during European sea bass development. (c) 2008 Elsevier B.V. All rights reserved.

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

The cardiac conduction system (CCS) is the component of the heart that initiates and maintains a rhythmic heartbeat. As the embryonic heart forms, the CCS must continue to develop and mature in a coordinated manner to ensure that proper pace making potential and distribution of action potential is maintained at all stages. This requires not only the formation of distinct and disparate components of the CCS, but the integration of these components into a functioning whole as the heart matures. Though research in this area of development may have lagged behind other areas of heart development, in recent years there has been much progress in understanding the ontogeny of the CCS and the developmental cues that drive its formation. This is largely due to studies on the avian heart as well as the use of molecular biology approaches. This review gives a perspective on advances in understanding the development of the vertebrate CCS, and reports new data illuminating the mechanism of conduction cell determination and maintenance in the mammalian heart. As much of our knowledge about the development of the CCS has been derived from the chick embryo, one important area facing the field is the relationship and similarities between the structure and development of avian and mammalian conduction systems. Specifically, the morphology of the distal elements of the mammalian CCS and the manner in which its components are recruited from working cardiomyocytes are areas of research that will, hopefully, receive more attention in the near future. A more general and outstanding question is how the disparate components of all vertebrate conduction systems integrate into a functional entity during embryogenesis. There is mounting evidence linking the patterning and formation of the CCS to instructive cues derived from the cardiac vasculature and, more specifically, to hemodynamic-responsive factors produced by cardiac endothelia. This highlights the need for a greater understanding of th

Members of the endothelin (Et) family of vasoconstrictors are highly homologous, 21 amino acid peptides with two conserved disulfide bonds (Cys1-Cys15THE OUTER DISULFIDE), and (Cys3-Cys11 INNER). To assess the importance of the outer disulfide bond, we synthesized a peptide in which the outer disulfide of Et-1 was replaced with an amide linkage. The resulting analog, Dpr1-Asp15 Et-1, potently inhibited Et-1 mediated vasoconstriction in the lung., This Article is from 'Peptides, Chemistry and Biology: Proceedings of the American Peptide Symposium (12th) Held in Cambridge, Massachusetts on 16-21 June 1991', AD-A256 113, p808-809.

This is an Author's Accepted Manuscript of: Liu, L., Urch, B., Poon, R., Szyszkowicz, M., Speck, M., Gold, D.R., ... & Silverman, F.S. (2015). Effects of ambient coarse, fine, and ultrafine particles and their biological constituents on systemic biomarkers: A controlled human exposure study in Environmental Health Perspectives, 123(6), 534-540. Available here.

Roberts L.A., Nosaka K., Coombes J.S., Peake J.M. (2014). Cold water immersion enhances recovery of submaximal muscle function after resistance exercise. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 307(8), R998-R1008. Available here