Ex vivo effects of bisphenol A or zearalenone on the prepubertal rat testis.

Bisphenol A (BPA) and zearalenone (ZEA) are two widespread xenoestrogens involved in male reproductive disorders. Few studies investigated the effects of these compounds on the prepubertal testis, which is highly sensitive to endocrine disruptors such as xenoestrogens. An ex vivo approach was performed to evaluate the effects of BPA or ZEA (10-11, 10-9, 10-6 M) on the testes of 20 and 25 dpp rats. To investigate the involvement of classical nuclear ER-mediated estrogen signaling in these effects, pre-incubation with an antagonist (ICI 182.780 10-6 M) was performed. BPA and ZEA have similar effects on spermatogenesis- and steroidogenesis-related endpoints in the immature testis, but our study highlights different age-dependent patterns of sensitivity to each compound during the prepubertal period. Moreover, our results indicate that the effects of BPA are likely to be induced by nuclear ER, whereas those of ZEA appear to involve other mechanisms.

Conservation in sequence and affinity of human and rodent PDGF ligands and receptors.

Platelet-derived growth factor (PDGF) consists of two chains, PDGF-A and -B, which activate as homo- or heterodimers two receptors, alpha and beta. To test PDGF function in vivo we have generated neutralizing monoclonal antibodies. When analyzed with rat PDGFs only antibodies raised against human PDGF-AA showed cross-species activity. This correlated with complete amino acid sequence conservation of PDGF-A whereas rat PDGF-B differed in six positions when cloned rat PDGF cDNAs were compared with their human homologs within the receptor binding region. Extracellular domains of cloned rat PDGF alpha- and beta-receptor cDNAs did not reflect this difference in cross-species ligand conservation. When rat extracellular domains were expressed as soluble proteins they bound human PDGF-BB with high affinity after immobilization of the purified proteins on solid phase. Dissociation constants were identical to those of their human homologs. Thus, high affinity binding of human PDGF-BB to extracellular domains does not depend on species origin but only on receptor type.

Cilazapril suppresses myointimal proliferation after vascular injury: effects on growth factor induction in vascular smooth muscle cells.

Smooth muscle cell proliferation and formation of extracellular matrix in the intima of muscular arteries after vascular injury can lead to severe intimal hyperplasia and stenosis. Cilazapril reduces intimal hyperplasia induced by balloon catheterization of the rat carotid artery by 80%, and significantly decreases the surface area covered by proliferative lesions. We investigated the effects of angiotensin II (A II) on SMC proliferation in cell culture and A-II induction of selected growth factor or growth-related genes in SMC in culture: PDGF A chain, TGF-beta, thrombospondin, c-myc and c-fos, and compared the influence of cilazapril on these responses to A II. A-II induced SMC proliferation, stimulated mRNAs for c-myc and c-fos after 30 min, and stimulated mRNAs for PDGF A chain, TGF-beta, and thrombospondin somewhat later. The ACE inhibitor did not have detectable independent effects on the A-II induced proliferation or gene expression. Thus, these data support the conclusion that cilazapril suppresses SMC proliferation in vivo through the block of conversion of A I to A II, and that A II has a critical and central role in the control of the proliferative response after balloon catheter-induced vascular injury.

Specific growth stimulation of cultured smooth muscle cells from spontaneously hypertensive rats by platelet-derived growth factor A-chain homodimer.

Cultured vascular smooth muscle cells (VSMC)1 from spontaneously hypertensive rats (SHR) possess specific cell surface receptors for both homodimeric forms of platelet-derived growth factor (PDGF-AA and PDGF-BB), in contrast to cells from normotensive Wistar Kyoto (WKY) animals, which express receptors only for the B-chain form of PDGF. Stimulation of quiescent VSMC from SHR with PDGF-AA resulted in activation of S6-kinase and induction of phosphoinositide catabolism, as well as cellular proliferation when cultures were maintained for prolonged periods with daily supplementation of the growth factor. WKY-derived VSMC showed no response to PDGF-AA, which was consistent with their lack of specific receptors for this homodimer. The responsiveness of quiescent cells from SHR and WKY to the B-chain homodimer was similar. The enhanced growth responsiveness of SHR-derived cells to fetal calf serum, as compared with cells from their normotensive counterparts, may be accounted for in part by their expression of receptors for the AA homodimer of PDGF.

The proliferative response to vascular injury is suppressed by angiotensin-converting enzyme inhibition.

Smooth muscle cell (SMC) proliferation and formation of extracellular matrix in the intima of muscular arteries are major processes that can lead to vascular stenosis in arteriosclerosis or after coronary angioplasty. These processes are also seen in the proliferative response to balloon catheter-induced vascular injury of the rat carotid artery, and result in marked neointima formation by 14 days after catheterization. We have shown recently that the angiotensin-converting enzyme (ACE) inhibitor cilazapril strongly suppressed this development of neointima. In this report, we show that the beneficial effects on neointima formation persist for at least 8 weeks after stopping treatment with cilazapril, and that continuous treatment may have additional inhibitory effects during the late phases of vascular remodeling after injury. To investigate further the possible mechanisms, we examined several vasoactive compounds in this model. Another ACE inhibitor of a different chemical class, captopril, reduced neointima formation as strongly as cilazapril (67 and 78%, respectively), but the calcium antagonist verapamil was not active as an inhibitor of neointima formation, despite similar lowering of blood pressure. Hydralazine and a new calcium antagonist, Ro 40-5967, partially suppressed neointima formation (36%, p less than 0.005 and 33%, p less than 0.05, respectively). In vitro, neither cilazapril nor its active metabolite, cilazaprilate, had any effect on SMC proliferation in response to serum or PDGF. To characterize further the role of angiotensin II (Ang II), we tested in cell culture the effects of Ang II and cilazaprilate on mRNA levels of several proteins potentially involved in regulating the SMC response.(ABSTRACT TRUNCATED AT 250 WORDS)

Both homodimeric isoforms of PDGF (AA and BB) have mitogenic and chemotactic activity and stimulate phosphoinositol turnover.

Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB, which were previously shown to bind to two receptors with different isoform-specificity, the A/B-type (binds all three isoforms) and the B-type (binds only PDGF-BB). Results from competition binding experiments with Swiss 3T3 cells suggest the existence of a third receptor type, which recognizes PDGF-AB and PDGF-BB. Furthermore, Swiss 3T3 cells and human dermal fibroblasts express different relative and absolute levels of these receptor types. In particular, Swiss 3T3 cells express 90,000 PDGF-AA binding sites (A/B-receptors) per cell, whereas human fibroblasts express only 20,000 A/B-receptors per cell. All three PDGF isoforms were tested in either cell type for their effect on DNA synthesis. PDGF-BB and PDGF-AA were also tested in Swiss 3T3 cells for their effect on inositol phospholipid metabolism and chemotaxis. Each isoform promoted all three processes dose-dependently, but there were differences in the maximum cellular responses elicited. These responses reflect the capacity of the cells to bind the individual isoforms. These results demonstrate that the previous distinctions in responsiveness to the different PDGF isoforms are primarily a consequence of the differences in the levels of surface expression of the various isoform-specific receptor types, rather than of the differences in the intrinsic activity of these isoforms. Furthermore, these results suggest that all types of PDGF receptors are capable of responding to their respective ligands by mediating phosphoinositide breakdown, chemotactic responses, and DNA synthesis. Whether they exhibit other functional differences remains to be seen.

Human vascular smooth muscle cells have at least two distinct PDGF receptors and can secrete PDGF-AA.

Platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant for smooth muscle cells and fibroblasts in culture, is believed to play an important role in the formation of proliferative lesions of arterio-sclerosis. PDGF appears as three different dimeric isoforms: AA, AB, and BB. These were recently found to bind to two different receptors, the A/B receptor (which binds all three isoforms) and the B receptor (which binds only PDGF-BB). To find out whether these receptors exhibit functional differences, we have monitored the binding and mitogenic activities of PDGF-AA and -BB in human umbilical vein smooth muscle cells (HSMCs), human dermal fibroblasts (HFs), and Swiss mouse 3T3 cells. With each cell type, there was a good correlation between the maximal levels of DNA synthesis achieved by these isoforms and the numbers of the appropriate receptor present on the cell surface: HMSCs, which have at least 32,000 B receptors but only 8,000 A/B receptors, responded well to PDGF-BB but responded poorly to PDGF-AA; whereas Swiss 3T3 cells, which have about equal numbers of B and A/B receptors (70,000 and 90,000, respectively), responded equally well to both isoforms. PDGF-AB was a more efficacious mitogen of HSMCs and HFs than was PDGF-AA and inhibited [125I]-PDGF-BB binding to HSMCs more effectively than PDGF-AA. This indicates that there may exist a third PDGF receptor type to which PDGF-BB and -AB but not PDGF-AA can bind.(ABSTRACT TRUNCATED AT 250 WORDS)

[Isolated rupture of the left main-stem bronchus during intubation with a Carlens tube]. / Rupture isolée de la bronche souche gauche lors d'une intubation par sonde de Carlens.

A case is reported of bronchial rupture due to a Carlens double-lumen tube. A 73 year old male patient was to undergo a double right lower and middle lobectomy for carcinoma. All went well and as expected until 20 min after the start of left-sided unilateral ventilation by way of the double-lumen tube. A sudden increase in the inspiratory pressures led to the discovery, first, of a leak around the cuff, and then, air bubbles in the mediastinum. Surgical exploration showed up the 4 cm long rupture in the pars membrana of the left main bronchus through which the cuff was herniating. The patient was reintubated and the rupture surgically repaired. The right upper lobe had not been ventilated for 45 min and there were signs of micro-atelectasia. The immediate postoperative course was rather stormy, with severe cardiac failure, recurring right upper lobe atelectasia and bilateral pulmonary infection. The patient was only definitely weaned from the respirator 40 days after the surgical incident. Although such complications with double-lumen tubes are rare, they must be recognized and surgically repaired very rapidly. A few simple rules to prevent these complications are discussed.

[Intravenous digital subtraction angiography in intensive care]. / Angiographie numérique par voie veineuse en réanimation.

Intravenous digital subtraction angiography (IVDSA) was performed in 11 patients aged from 23 to 62 yr to visualize vascular disease that required to be treated without delay: 7 were in shock preceded by a cardiac arrest in 5 of them; 4 suffered from acute renal failure, 8 from acute respiratory failure and one from brain death. 5 pulmonary, 2 thoracic aortic, 3 abdominal aortic, 1 right subclavian and 1 renal arterial angiographies were carried out by this method. In all the cases described, we either confirmed the diagnosis (rupture of thoracic aorta, type I aortic dissection, aneurysm of abdominal aorta, complete occlusion of the distal abdominal aorta, pulmonary embolism) or set aside diagnosis (lesion of the subclavian vessels, pulmonary embolism) or visualized the renal vasculature before removing the organ. No incident was observed. Conventional angiography remained a reference method but it presented risks which were not to be neglected in critically ill patients. Despite the theoretical limits set by the technical demands (absolute motionlessness, apnoea) and few other restrictions found in the literature, IVDSA seemed to offer distinct advantages under such conditions. Only requiring an injection using a catheter placed in a peripheral vein, this method was fast, safe and easy; it gave a close enough approach to the diagnosis to be able to help decide on specific treatment or on orientation towards a specific hospital department.

[Method for prolonged hemodynamic and respiratory monitoring. I. Technical study involving 45 patients]. / Méthode de surveillance hémodynamique et respiratoire prolongée. Etude technique portant sur 45 sujets.

The authors describe a method for haemodynamic and respiratory surveillance which they applied to 45 severely ill patients in circulatory and/or respiratory distress. Only an arterial and central venous catheter are necessary. They are used to measure arterial and venous blood gas levels as well as cardiac output by dye dilution. Long term surveillance is made possible by the absence of a Swan-Ganz catheter. Periods were as 7 to 35 days with a mean of 12.6 days, during which 910 assessments were made with the use of 64 arterial catheters and 71 venous catheters. The method reduces the prevalence of itrogenic accidents complicating the course of these severely ill patients and considerably lowers the cost of such surveillance. No specifically related complications were seen, problems being limited to the usual percentage of complications due to arterial and venous catheters.