Biomedical subjects

G Pascual

Publications and source records attributed to G Pascual.

At least 19 recordsLinked to original sources

PubMed2006

Efficiency of 4% icodextrin in preventing adhesions to spiral tacks used to fix intraperitoneal prostheses.

BACKGROUND/AIMS: This study was designed to evaluate the extent of adhesion formation to prostheses fixed with spiral tacks and to establish whether the use of Ringer's lactate or icodextrin could prevent these adhesions. METHODS: 24 New Zealand white rabbits weighing around 3,000 g were implanted with a 7 x 5 cm patch of ePTFE (DualMesh) through a midline laparotomy. The prosthesis was fixed to the intact peritoneum using spiral tacks. Three study groups were established according to whether the animals were: implanted with ePTFE fixed with spiral tacks or implanted with ePTFE fixed with spiral tacks and simultaneously administered Ringer's lactate or 4% icodextrin in the peritoneal cavity. Adhesion formation and prosthetic behavior at the prosthesis/peritoneal interface were evaluated and quantified by sequential laparoscopy performed at 3, 7 and 14 days. RESULTS: Adhesions generally formed on the tacks and were classified as the fully integrated type. No significant differences were observed in terms of the extent of adhesions or of neoperitoneal thickness between control animals and those receiving Ringer's lactate or icodextrin. CONCLUSIONS: (a) Prosthesis-fixing tacks induced adhesions; (b) the use of substances such as icodextrin or Ringer's lactate does not seem to diminish adhesion formation, and (c) the use of icodextrin offered no benefits over that of Ringer's lactate solution.

Animals↗

PubMed2006

Influence of the structure of new generation prostheses on shrinkage after implant in the abdominal wall.

When a biomaterial is used to repair an abdominal wall defect, wound contraction can cause the prosthesis to shrink, and the tension generated can provoke recurrence of the defect. This study was designed to determine whether the structure of a prosthesis can directly influence prosthetic shrinkage. Abdominal wall defects (7 x 5 cm) in rabbits were repaired using the laminar prosthesis DualMesh (DM), the composites Sepramesh (Se) and Vypro II (Vy), and the reticular prosthesis Surgipro (PP). The animals were sacrificed 14 and 90 days after surgery, at which time implant specimens were morphologically and immunohistochemically examined to establish the presence of myofibroblasts and macrophages. The size of each prosthesis was measured at the end of the study through image analysis. Morphometric measurements revealed greatest prosthesis shrinkage for Se, PP, and Vy (16.05% +/- 5.08%; 13.75% +/- 4.22%; 16.16% +/- 6.34%), while the DM prostheses only showed a 7.57% +/- 0.62% decrease in size (p < 0.05). In the DM implants, the macrophage response and myofibroblast labeling were reduced. Both biomaterial structure and the macrophage reaction induced at the implant site modulate prosthetic shrinkage, laminar prostheses of the ePTFE type undergoing less shrinkage than reticular meshes. Reduced DM shrinkage was linked to decreased myofibroblast numbers 2 weeks postimplant.

Abdominal Injuries↗

PubMed2005

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component.

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP + h) or Vicryl (PP + v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08 +/- 5.09, PP + h: 18.55 +/- 4.96, P + v: 69.69 +/- 16.81%), neoperitoneal thickness (PP: 256.17 +/- 21.68, PP + h: 83.11 +/- 19.63, PP + v:213.72 +/- 35.90 microm) and macrophage counts (PP: 8.73 +/- 1.16, PP + h: 27.33 +/- 4.13, PP + v: 31.24 +/- 3.08%) showed significant differences (P < 0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP + h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.

Abdominal Wall↗

PubMed2005

Composite prostheses used to repair abdominal wall defects: physical or chemical adhesion barriers?

In a composite prosthesis, the component placed at the peritoneal interface takes the form of a physical or chemical barrier. In this experimental study performed on the white New Zealand rabbit, several composites were examined to establish the effectiveness of these barriers at impeding adhesion formation. The biomaterials tested were two polypropylene prostheses (PP) with the physical barriers of expanded polytetrafluoroethylene or polyurethane (PP + ePTFE and PP + PU) and two prostheses (one polyester and the other PP) with the absorbable chemical barriers of polyethylene glycol/glycerol and hyaluronate, respectively (PO + gl and PP + hy). The composites were used to repair 7 x 5 cm defects created in the abdominal wall of the animals by placing the implant in contact with the visceral peritoneum and the subcutaneous tissue and fixing it to recipient tissue by 4/0 polypropylene running suture. Fourteen days after surgery the animals were sacrificed and specimens were taken for light microscopy and scanning electron microscopy. Adhesions developing at the prosthesis/visceral peritoneal interface were quantified. All the prostheses induced optimal mesothelialization. Composites with physical barriers behaved similarly in terms of provoking adhesions. However, the prostheses with chemical barriers differed in their effectiveness at preventing adhesions. Overall, the best results were obtained with the PP + PU composite.

Abdominal Wall↗

PubMed2005

Patency and structural changes in cryopreserved arterial grafts used as vessel substitutes in the rat.

OBJECTIVE: To evaluate the patency and structural changes that occur in the short- and mid-term when cryopreserved syngenic arterial grafts are implanted in an experimental animal model. MATERIAL AND METHODS: Segments of iliac artery from the Spraque-Dawley rat were cryopreserved in a biological freezer according a controlled, computerized freezing protocol whereby the specimens are cooled at a rate of 1 degrees C/min. After storage at -145 degrees C in liquid N2 vapor for 30 days, the cryografts were slowly thawed. These vessels were grafted to the common iliac artery in syngenic animals. The following study groups were established: group I (GI), non-implanted cryografts; group II (GII), autografts; and group III (GIII), cryoisografts. The control group (CG) was comprised of fresh iliac arteries. The animals were sacrificed 14, 30, or 90 days post-surgery. At each of these follow-up times, graft specimens were morphologically evaluated by light and scanning and transmission electron microscopy and immunolabeling of endothelial cells (vWf). Cell damage attributed to the cryopreservation or grafting process was also determined. RESULTS: At the time of sacrifice, graft patency was 100% for the autografts, while 26.6% of the cryoisografts showed fully occlusive thrombosis. Among other complications, two pseudoaneurysms were detected. After cryopreservation, the grafts (GI) showed patches of endothelial denudation and good cellularity of the medial layer. The intimal hyperplasia observed in autografts implanted for 14 days (GII) was significantly delayed until day 30 when the graft was cryopreserved (GIII). Cryoisografts showed general thinning of the arterial wall and degeneration accompanied by medial layer cell loss. These grafts showed most cell damage at 90 days post-implant. Expression of the vWf in all specimens showing intimal hyperplasia was confined to the outermost graft layer. CONCLUSIONS: Cryopreservation modified the reparative response of the grafts. Owing to faster degeneration of the medial layer and a delay in the appearance of intimal hyperplasia, arterial wall thickness was reduced relative to that of the non-cryopreserved autografts. This thinning, at least in the short-term (90 days), does not seem to give rise to aneurysms owing to the generation of a neointima that stabilizes the vessel wall.

Animals↗

PubMed2005

Histological evaluation of scar tissue inflammatory response: the role of hGH in diabetic rats.

This paper describes a polymer site-specific delivery system containing human growth hormone in an in vivo model of scarring in the diabetic state. Copolymer discs with the hormone were introduced into incisions made in rats previously injected with streptozotocin in order to induce diabetes. Tissue specimens for evaluation were obtained at 3, 7 or 10 days after the procedure. Study groups were healthy rats and diabetic rats untreated or treated with/without the hormone. Histological sections were prepared for light microscopy examination of wound zones. Three and 7 days after surgery, polymer remains could be observed in the subcutaneous tissue. These remnants induced a moderate foreign body reaction. The number of macrophages detected was directly related to neovessel formation and metalloelastase expression. The CD4+/CD8+ ratio was low during the initial follow up stages (3 and 7 days) in untreated diabetic rats, yet an increased ratio corresponding to areas around the polymer remains was noted in the animals treated with copolymer loaded with the growth hormone. Copolymer is biodegradable in vivo and may be used as a vehicle for the slow release of active substances. The presence of the hormone at the site of skin injury induces cell proliferation and enhances the repair process.

Animals↗

PubMed2005

Muscle-derived stem cells in tissue engineering: defining cell properties suitable for construct design.

The terms construct or tissue equivalent refer to neotissue produced by tissue engineering techniques. The elements forming the construct are scaffolds on which cells are "recreated" to form an engineered-tissue sensitive to certain cell signals. The ability of the cells to expand and differentiate on the scaffold is determined by properties such as fixation, adhesion, proliferation and migration. Among the cell types that seem to be most promising for designing constructs are tissue-residing, or adult, stem cells, which show two main features: a capacity to differentiate into many cell lineages and the power of self-renewal. These features make them good candidates for cell replacement therapies. Here, we report the identification, isolation and culture of muscle stem cells aimed at establishing the ideal culture in terms of defining when the cultured cell population would show optimal characteristics for transfer to the scaffold to obtain a particular construct. Stem cells harvested from the dorsal muscle of white New Zealand rabbits were cultured in vitro and characterized 5 to 14 days after the start of culture. Fibroblasts obtained from the same experimental animal served as controls. The stem cells were examined by light and scanning electron microscopy. For stem cell identification, we used the antibodies anti-m-cadherin, anti-CD34 and anti-Myf-5. The markers of muscle differentiation used were: anti-vimentin, anti-alpha-actin, anti-desmin and anti-myosin. The expression profiles of the different markers of muscle differentiation and TGFbeta1 in the cell cultures were confirmed by Western blotting. Proliferation rates were determined by monitoring tritiated thymidine incorporation. The thymidine incorporation rate was substantially higher for the population of undifferentiated cells than for control fibroblasts obtained from the same animal. During the first five days of culture, most cells were negative for all the markers examined, with the exception of m-cadherin, CD34 and Myf-5, although discrete signs of vimentin expression started to emerge. After 14 days of culture, the adult stem cells showed vimentin (94.2%) and desmin (33.8%) expression yet scarce labeling for myosin (16.2%) and alpha-actin (8.3%). Control fibroblasts showed intense labeling for vimentin (99.3%) and alpha-actin (62.2%), while less than 2% of the population expressed myosin (0.9%) and desmin (1.6%). After two weeks of culture, muscle-derived stem cells show good proliferative and adhesion properties as they initiate differentiation. These conditions seem ideal for obtaining the desired construct.

Actins↗

PubMed2004

Long-term behaviour of cryopreserved arterial grafts versus prosthetic micrografts.

INTRODUCTION: When a patient has no suitable vessels for use as grafts in bypass or reconstruction procedures, two of the options available are the use of a cryopreserved vessel or an expanded polytetrafluoroethylene (ePTFE) prosthesis. This study was designed to compare the long-term behaviour of these vascular substitutes. MATERIAL AND METHODS: We established three study groups by grafting the following vessel substitutes to the iliac artery in Spraque-Dawley rats: arterial autografts (GI, n=12), cryopreserved syngenic arterial grafts (cryoisografts) (GII, n=12), and ePTFE micrografts (GIII, n=12). The animals were sacrificed 180 days after surgery, at which time the graft specimens were morphologically evaluated by light and electron microscopy, immunolabelling (ED1/alpha-actin) and morphometric analysis of the neointima. RESULTS: At the time of sacrifice, graft patency was 100% for the autografts and cryoisografts, while 10% of the ePTFE micrografts showed fully-occlusive thrombosis. Intimal hyperplasia was observed in grafts in GI and GII; the neointima being thinner in the cryoisografts (54.36 +/- 2.26 microm) than the autografts (161.30 +/- 3.91 microm). The endothelium formed over the prosthetic micrografts was unstable, with areas of subendothelial thickening (9.37 +/- 3.18 microm). Cell loss and medial layer degeneration were observed in both GI and GII specimens, while the GIII grafts were colonised by cells on their luminal surface. CONCLUSIONS: All three grafts show good long-term tolerance when used in an arterial setting. Following long-term implant, autografts and cryoisografts show similar alterations that give rise to the complete loss of the muscle component of the tunica media along with the formation of a stable neointima. This new layer takes on the role of the tunica media.

Animals↗

PubMed2003

Modulatory role of IL10 in endothelial cell damage and platelet adhesion.

This study explores the possibility of a regulatory role for cytokine IL-10 in platelet aggregation as an active vascular repair mechanism. Endothelial cells from human umbilical cord vein were cultured in the presence of different IL-10 concentrations (0-100 ng/ml). Platelet-rich plasma was then added to these cultures and allowed to act for 30 minutes. To rule out blood plasma involvement, washed platelets were also incubated with IL-10 (0-100 ng/ml). Changes in endothelial cell morphology were observed depending on the IL-10 concentration used; apoptotic cells appearing at the highest IL-10 concentration. Greatest platelet adhesion was noted at the highest IL-10 concentration. It was concluded that, in this in vitro model, low IL-10 levels do not affect cell viability or the pattern of platelet adhesion, but at high doses, this cytokine induces cell death and enhances platelet deposition.

Apoptosis↗

PubMed2002

The use of ischaemic vessels as prostheses or tissue engineering scaffolds after cryopreservation.

OBJECTIVE: to evaluate the condition of organ donor arteries subjected to prolonged cold-ischaemia followed by cryopreservation, for their possible use as vascular grafts. MATERIALS AND METHODS: fresh specimens of human iliac artery from organ donors were used as controls. These arteries were divided into two portions, one of which was cryopreserved in an automated freezer. A further group of arteries was immersed in Wisconsin solution and kept for 4 days at 4 degrees C (cold-ischaemia). After this period, the arteries were also cut into two, and one of these portions was cryopreserved. All the cryopreserved arterial segments were stored for a month and then subjected to automated gradual thawing. The thawed specimens were evaluated by light microscopy, scanning and transmission electron microscopy, immunohistochemical analysis (MMPs, elastin, CD31, von Willebrand factor) and the in situ detection of fragmented DNA (TUNEL method). RESULTS: the most marked changes induced by cryopreservation were partial vessel deendothelialisation and morphological changes in cells of the intima that were in the process of detachment. No significant changes were observed in the medial layer, other than discrete elastic fibre fragmentation. Following cold-ischaemia, the endothelium was the most affected layer, with large denuded areas and exposure of the fibroelastic layer. Increased MMP-2 expression was also noted after cold-ischaemia. When subjected to both cold-ischaemia and cryopreservation, a large proportion of endothelial cells showed positivity for the TUNEL technique, however, no significant difference was observed between the ischaemic and the ischaemic/cryopreserved specimens. CONCLUSIONS: prolonged cold-ischaemia causes some additional damage to the arterial wall compared to cryopreservation alone. However, the structural component of the ischaemic vessel remains in a condition that is suitable for subsequent cryopreservation and use as a vessel substitute or a scaffold for tissue engineering.

Adult↗

PubMed2001

Gradual thawing improves the preservation of cryopreserved arteries.

This study was designed to test a slow, controlled, automated process for the thawing of cryopreserved arteries, whereby specimen warming is synchronized with the warming of its environment. Segments of minipig iliac artery, 4-5 cm in length, were subjected to controlled, automated cryopreservation in a biological freezer at a cooling rate of 1 degrees C/min to -120 degrees C, followed by storage in liquid nitrogen at -196 degrees C for 30 days. Following storage, the arterial segments were subjected to rapid (warming rate of approximately 100 degrees C/min) or gradual (1 degrees C/min) thawing. Thawed specimens were processed for light microscopy and for scanning and transmission electron microscopy, Cell death was determined by the TUNEL method. Metalloproteinase (MMP) expression was estimated by immunohistochemical analysis. Most of the cryopreserved vessels subjected to rapid thawing showed spontaneous fractures, mainly microfractures, whereas these were absent in slowly thawed specimens. In rapidly thawed vessels, the proportion of damaged cells was double that observed in those thawed more gradually. Increased intensity and extent of MMP-2 expression was shown by rapidly thawed specimens. The slow-thawing protocol tested avoids the formation of spontaneous fractures and microfractures and the accumulation of fluid within the arterial wall tissue. This results in improved tissue preservation.

Animals↗

PubMed2001

Effect of the thawing process on cryopreserved arteries.

This study was designed to explore the changes that occur in cryopreserved pig arteries following different thawing procedures, before and after being placed in an in vitro flow circuit. Segments of minipig iliac artery were cryopreserved in complete minimal essential medium plus 10% dimethylsulphoxide and stored in liquid nitrogen at -196 degrees C for 30 days. Three study groups were established according to whether the arterial specimens were fresh (control, n = 20), cryopreserved and rapidly thawed (RT) at 37 degrees C (n = 22) or cryopreserved and subjected to controlled, automated slow thawing (ST) (n = 22). Half of the specimens of each group were subsequently placed in the flow circuit for 72 hr. Evaluation was made of morphological and ultrastructural changes. Cell damage was established using the TUNEL method. All cryopreserved specimens showed endothelial denudation that was most extensive in those subjected to rapid thawing. Slowly thawed specimens showed improved cell viability and organization of the vessel wall, compared to those thawed rapidly. Under conditions of flow, the damage induced by the freezing/thawing process was enhanced. These findings suggest that (a) slow thawing of cryopreserved arteries results in improved preservation of the structure and viability of vessels, and (b) the damage induced by freezing/thawing is enhanced when vessels are subjected to flow in an in vitro circuit.

Animals↗

PubMed2001

Fibroblasts from the transversalis fascia of young patients with direct inguinal hernias show constitutive MMP-2 overexpression.

OBJECTIVE: To determine the expression pattern of certain metalloproteinases (MMPs) known to be involved in the degradation of the extracellular matrix in cultured fibroblasts from the transversalis fascia (TF) of patients with inguinal hernia. SUMMARY BACKGROUND DATA: Inguinal hernia is a common pathology, the cause of which remains unknown. It is, however, clear that the TF is one of the anatomical structures that may impede the formation of hernias, and particularly the direct type of hernia. In previous studies the authors found enhanced MMP-2 expression in TF specimens in vivo. The persistence of increased expression in cultured fibroblasts might support the idea of a genetic defect as the cause for this pathology. METHODS: Fibroblasts from the TF of patients with direct and indirect inguinal hernia were cultured and compared with those obtained from control TF in terms of MMP (MMP-2 and MMP-9) expression. RESULTS: Significant active MMP-2 expression was shown by TF fibroblasts from young patients with direct hernias. These findings were confirmed by immunosorbent assay, immunoblotting, and zymography of the fibroblast culture media. No MMP-9 expression was detected. CONCLUSION: These results indicate that MMP-2 may be involved in the TF matrix degradative process in patients with direct hernia. The persistence of changes in MMP-2 levels in the cell cultures appears to suggest a genetic defect or irreversible change as the origin of this pathology rather than environmental factors, which may later participate in the development of the hernial process.

Adult↗

PubMed2000

15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway.

Prostaglandin J(2) (PGJ(2)) and its metabolites Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) are naturally occurring derivatives of prostaglandin D(2) that have been suggested to exert antiinflammatory effects in vivo. 15d-PGJ(2) is a high-affinity ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma) and has been demonstrated to inhibit the induction of inflammatory response genes, including inducible NO synthase and tumor necrosis factor alpha, in a PPARgamma-dependent manner. We report here that 15d-PGJ(2) potently inhibits NF-kappaB-dependent transcription by two additional PPARgamma-independent mechanisms. Several lines of evidence suggest that 15d-PGJ(2) directly inhibits NF-kappaB-dependent gene expression through covalent modifications of critical cysteine residues in IkappaB kinase and the DNA-binding domains of NF-kappaB subunits. These mechanisms act in combination to inhibit transactivation of the NF-kappaB target gene cyclooxygenase 2. Direct inhibition of NF-kappaB signaling by 15d-PGJ(2) may contribute to negative regulation of prostaglandin biosynthesis and inflammation, suggesting additional approaches to the development of antiinflammatory drugs.

Animals↗

PubMed2000

Evaluation of the acute scarring response to the implant of different types of biomaterial in the abdominal wall.

Since the short-term, acute scarring process induced by a biomaterial may condition the evolution of the repair process, the present investigation evaluates the behavior of polytetrafluoroethylene (PTFE) and polypropylene (PL) biomaterials in the initial stages of repair. Three PTFE biomaterials (Mycro Mesh, Dual Mesh and Soft Tissue Patch) and one PL biomaterial (Marlex) were employed to repair defects created in the abdominal wall of New Zealand rabbits. Animals were sacrificed at 3 or 7 days. Specimens were obtained for light and scanning electron microscopy, and immunohistochemical analysis using the RAM-11 monoclonal antibody for rabbit macrophages. The PL implants showed substantial adhesion formation with viscera. Lower adhesion formation was detected in the PTFE implants. The evolution of the acute phase of the repair process was similar for each PTFE biomaterial. At 3 days post implant, an incipient neoperitoneum was detected which was fully established after 7 days. The behavior of the PL implant was similar, although a greater amount of reticular granulation was detected. The neoformed peritoneum was irregular. Few RAM-11-labeled macrophages were detected in all cases. The acute phase of the tissue repair process induced by the implant of PTFE and PL biomaterials generally proceeds along similar lines to a normal repair process. However, the use of microporous, laminar materials seems to favor the early establishment of a well-defined neoperitoneal layer.

Journal Article↗

PubMed2000

Rapid thawing increases the fragility of the cryopreserved arterial wall.

OBJECTIVE: To extend present knowledge of the biomechanical and structural changes which occur in the cryopreserved, rapidly thawed arterial wall. MATERIALS AND METHODS: Minipig iliac arterial segments were cryopreserved at -196 degrees C in either minimum essential medium or Wisconsin solution. Fresh segments served as the control group. After 1 month, the specimens were rapidly thawed (37 degrees C) and processed for biomechanical, ultrastructural, morphological and immunohistochemical (MMP-1, MMP-2, MMP-3 and MMP-9) analysis. Visualisation of apoptotic cells was performed by TUNEL method. For the mechanical distension analysis, an in vitro circuit was designed. RESULTS: The cryopreserved segments showed a 42% incidence of spontaneous fracture and the appearance of microfractures which affected the endoluminal third of the vessel. An accumulation of liquid in the subelastica was observed. An increased expression of wall-degradative enzymes (mainly MMP-2) was also observed following cryopreservation. No significant differences were detected in the proportional elasticity module or tensile strength of the specimen groups. No differences in mechanical distension were observed between groups after the vessel segments were subjected to the pulsatile circuit flow for 72 h. Cell damage was most intense in the specimens cryopreserved in Wisconsin solution. CONCLUSIONS: Cryopreservation in both the solutions employed, followed by rapid thawing, induce changes in the permeability which increase the fragility of the cryopreserved arterial wall. Both increased expression of wall-degradative enzymes and accumulation of liquid may contribute to graft failure after implantation.

Adenosine↗

PubMed2000

Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily that activates target gene transcription in a ligand-dependent manner. In addition, liganded PPARgamma can inhibit transcription of genes induced by gamma interferon (IFN-gamma) and/or lipopolysaccharides (LPSs), including the inducible nitric oxide synthase (iNOS) gene. Inhibition of the iNOS promoter is achieved partially through antagonizing the activities of NF-kappaB, AP-1, and STAT1, which are known to mediate effects of LPS and IFN-gamma. Previous studies have suggested that transrepression of these factors by nuclear receptors involves competition for limiting amounts of the general coactivators CREB-binding protein (CBP) and p300. CBP and p300 are thought to be recruited to nuclear receptors through bridging factors that include SRC-1, although CBP also interacts directly with PPARgamma through its amino terminus. These observations have raised questions concerning the involvement of SRC-1-like factors in CBP recruitment and transrepression. We here provide evidence that PPARgamma's ability to repress iNOS transcription requires the ligand-dependent charge clamp that mediates interactions with CBP and SRC-1. Single amino acid mutations in PPARgamma that abolished ligand-dependent interactions with SRC-1 and CBP not only resulted in complete loss of transactivation activity but also abolished transrepression. Conversely, a CBP deletion mutant containing the SRC-1 interaction domain but lacking the N-terminal PPARgamma interaction domain was inactive as a PPARgamma coactivator and failed to rescue transrepression. Together, these findings are consistent with a model in which transrepression by PPARgamma is achieved by targeting CBP through direct interaction with its N-terminal domain and via SRC-1-like bridge factors.

Animals↗

PubMed2000

Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall.

This study was designed to evaluate the role of the smooth muscle cell and the apoptosis in the pathogenesis of the varicose vein. Segments of saphenous vein were obtained from healthy subjects and from those with varicose veins. The vein specimens were subdivided according to subject age (younger or older than 50 years) and according to the varicose vein source (distal or proximal). Morphological, ultrastructural, cell proliferation (anti-PCNA method) and cell death (TUNEL method) analysis were performed. The walls of healthy, control vein specimens acquired a more collagenous and papillomatous appearance with age. A slight increase in the number of TUNEL-positive cells was also observed in specimens from older subjects. The proportion of apoptotic cells was much greater in the varicose veins than in control specimens. Most cellular alterations were seen in proximal varicose segments obtained from young subjects. These specimens showed hypertrophic areas with a high degree of cellularity (both in the media and in the thickened intima). The highest proportion of apoptotic cells and collagenisation were also observed in these areas. The enhanced number of apoptotic cells in varicose veins observed mainly in proximal/young vein specimens could be responsible, at least in part, for the acceleration of the final fibrosclerotic process characteristic of the varicose vein wall.

Adult↗