Microbiologic contamination during dental radiographic film processing

Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model of arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 mg/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 mg/kg body wt per hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, and intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells and decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)     

DNA requirements in vivo for phage T4 packaging

OBJECTIVE: We sought to determine the morphology, mechanisms of deterioration, cellular viability, extracellular matrix integrity, and the role of immune responses in the dysfunction of cryopreserved aortic and pulmonic valve allografts. METHODS: We studied 33 explanted left-sided (n = 20) or right-sided (n = 13) cryopreserved human allograft heart valves explanted several hours to 9 years after operation, 14 nonimplanted allografts, and 16 aortic valves removed from transplanted allograft hearts 2 days to 4 years after operation. Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies. RESULTS: Allografts implanted for more than 1 day had progressive collagen hyalinization and loss of normal structural complexity and cellularity, including endothelium and deep connective tissue cells. Inflammatory cells were generally minimal or absent in the allografts. Transmission electron microscopy of long-term cryopreserved allograft valves revealed no viable cells, focal calcification centered around dead cell remnants, and distorted but preserved collagen. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including endothelium and abundant deep connective tissue cells; inflammatory infiltrates were generally mild and of no apparent deleterious consequence, including valves from patients who died of fatal rejection. CONCLUSIONS: Cryopreserved allografts are morphologically nonviable; their collagen is flattened but largely preserved. They are unlikely to grow, remodel, or exhibit active metabolic functions, and their usual degeneration cannot be attributed to immunologic responses. In contrast, aortic valves of transplanted hearts maintain near-normal overall architecture and cellularity and do not show apparent immunologic injury, even in the setting of fatal myocardial parenchymal rejection or graft arteriosclerosis.     

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model

Although matrix metalloproteinases (MMPs) are expressed in abundance in arterial aneurysms, their contribution to arterial wall degeneration, dilation, and rupture has not been determined. We investigated MMP function in a rat model of aneurysm associated with arterial dilation, elastin loss, medial invasion by mononuclear inflammatory cells, and MMP upregulation. Rupture was correlated with increased gelatinase B (MMP-9) and activated gelatinase A (MMP-2). Syngeneic rat smooth muscle cells retrovirally transfected with tissue inhibitor of matrix metalloproteinases (TIMP)-1 cDNA (LTSN) or with the vector alone as a control (LXSN) were seeded onto the luminal surface of the vessels. The seeding of LTSN cells resulted in TIMP-1 local overexpression. The seeding with LTSN cells, but not LXSN cells, decreased MMP-9, activated MMP-2 and 28-kD caseinase and elastase activity, preserved elastin in the media, and prevented aneurysmal degeneration and rupture. We conclude that MMP overexpression is responsible for aneurysmal degeneration and rupture in this rat model and that local pharmacological blockade might be a reasonable strategy for controlling the formation of aneurysms in humans.     

Manometry of individual segments of the distal esophageal sphincter. Its relation to functional incompetence

The morphology of the arteries in the uterine wall was studied in three multiparous aged mares that had suffered repeated pregnancy failure. The uterine wall arteries exhibited elastosis of the intima or adventitia, or both, resembling "physiological pregnancy sclerosis". In areas affected by elastosis, degeneration of the pre-existing elastic fibres and increased glycosaminoglycans were frequently observed. Newly formed elastic fibres were not evident. Delayed resorption due to disordered metabolic turnover of the elastin was thought to be an important factor in the pathogenesis of the arterial elastosis in the uterine wall.     

Elastin of the umbilical cord arteries and its alterations in EPH gestosis (preeclampsia)

Edema, proteinuria, hypertension (EPH) gestosis is accompanied by an increase of collagen content and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in the umbilical cord arteries and in Wharton's jelly. The effect of EPH gestosis on elastin content and metabolism in the umbilical cord arterial wall was the aim of this work. Studies were performed on normal umbilical cord arteries and those taken from newborns of mothers with EPH gestosis. Elastin was isolated from the arterial wall and quantified by a dye-binding method. Biosynthesis and degradation of this protein was evaluated by a pulse-chase experiment with the use of 14C-proline. It was found that EPH gestosis is associated with a significant reduction of elastin content in the umbilical cord arteries as a result of decrease in elastin biosynthesis rate and accelerated degradation of this protein. The replacement of elastin by collagen, and hyaluronate by sulfated glycosaminoglycans, may decrease the hydration of arterial wall and reduce its elasticity. Such rearrangement of extracellular matrix of the umbilical cord arteries may affect mechanical properties of these vessels and disturb fetal blood circulation.     

Speed, sex, gay men, and HIV: ecological and community perspectives

OBJECTIVE: To find a means of bladder augmentation that would avoid the complications encountered with the use of bowel segments, using a newly developed acellular biomaterial, the bladder acellular matrix graft (BAMG), as a homologous graft. MATERIALS AND METHODS: Thirty-four rats underwent a partial cystectomy (40-50%) and grafting with a BAMG of equal size. Eleven rats died within the first 72 h. probably from urinary leakage caused by obstruction of the bladder neck with stones or coagula; the surviving 23 were killed at varying intervals after cystectomy and examined. RESULTS: After providing initial bladder enlargement, the graft was progressively infiltrated by the vessels and smooth muscle cells of the host: furthermore, the mucosal lining was complete within 10 days. After 4 weeks, all bladder wall components were evident histologically in the graft. The ingrowth was complete after 8 weeks, except for neural regeneration, which was only partial. At 12 weeks, the bladder wall muscle structure in the graft was so well developed that it was difficult to delineate the junction between host bladder and BAMG. Neural regeneration continued to improve. Normal bladder capacities were maintained throughout the study. CONCLUSION: The BAMG appears to serve, without rejection, as a framework of collagen and elastin for the ingrowth of all bladder wall components. The reason for the better acceptance of the BAMG than of other bladder augmentation grafts requires further investigation.     

Adventitial stripping does not strip the adventitia

This study investigates the process of stripping the adventitia off a blood vessel, which is a normal procedure prior to performing a microvascular anastomosis. In five rats, the common carotid and the superficial femoral arteries of one side were stripped sharply, whereas the arteries of the other side were left unstripped to serve as controls. In a further set of five rats, the arteries were stripped bluntly. Immediately following stripping, experimental and control arterial segments were removed. Histology of cross sections of the segments was studied. In no case was there complete removal of the adventitia. When stripped and control arterial sections were compared, no significant difference between cross-sectional adventitial areas could be demonstrated. Morphologic study revealed that stripping mainly removes large collagen fibers from the adventitia. The small collagen fibrils that are still in place fan out in such a way that although considerable tissue is removed, the volume that the adventitia occupies remains the same. Stripping the adventitia does not cause complete removal of the adventitia, and in this study no significant reduction in the adventitial volume could be found. Stripping does, however, allow a better view of the cut edge of the vessel wall under an operating microscope. Since blunt stripping could cause damage to other vessel wall layers, sharp stripping is to be preferred.     

Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer

Although it has been claimed that allografts of blood vessels might be successful because of minimal immunogenicity, they are subject to frequent and early failure, the cause of which has not been thoroughly investigated. We sought to define the immune response to allograft bypass. In a prospective trial, 40 patients underwent cryopreserved venous allograft bypass. Allograft biopsies were performed at implantation and at allograft explantation in instances of graft failure. Tissues were evaluated in a blinded manner by means of standard histologic examination and paraffin immunohistochemical analysis with monoclonal antibodies against a variety of immune markers. During the 31-month follow-up period, 22 allografts were removed, and 19 were suitable for immunohistochemical study. Of these 19, 6 (32%) had moderate or severe infiltrates, which were evenly distributed throughout the intima, media, and adventitia. Immunohistochemical study of the explants demonstrated all of these infiltrates to be leukocytes (+LCA), which were predominantly activated T lymphocytes (+CD3, CD8, CR3) containing cytotoxic granules (+TIA-1). Macrophages were uncommon (+CD68); B cells (+L26, CD79) and natural killer cells (+CD56) were rare. Immunosuppression was associated with decreased presence of cytotoxic granules (TIA-1). Human venous allografts are immunogenic and prompt a T cell-mediated response. Allografts also fail without strong evidence of rejection, presumably because of local injury, hypercoagulability, or stasis. It may be possible to modify the contribution of rejection to venous allograft failure by means of immunosuppression and to modify the contribution of local hypercoagulability by means of anticoagulation.     

Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.     

Wound healing: a paradigm for lumen narrowing after arterial reconstruction

PURPOSE: The intimal hyperplasia hypothesis that equates lumen narrowing after arterial injury with intimal mass has recently been challenged. Evidence has emerged to suggest that lumen narrowing is caused in large part by changes in artery wall geometry rather than intimal mass per se. We have begun to explore this hypothesis in a unique nonhuman primate model of atherosclerosis. METHODS: Monkeys who were fed an atherogenic diet for 3 to 5 years underwent experimental angioplasty of the left iliac artery. The contralateral iliac artery served as an intraanimal control. Arteries were removed 2, 4, 7, 14, 28, or 112 days later for analysis (6 or 13 per time point). Angioplasty dilated arteries by fracturing atheroma and stretching or tearing the media. Cross-sections of injured arteries were analyzed for expression of extracellular matrix components and cell surface integrins that are important in wound healing. Antibodies, riboprobes, or histochemical stains specific for fibrin, hyaluronan, versican (chondroitin sulfate-containing proteoglycan), procollagen-I, elastin, and the alpha 2 beta 1 and alpha V beta 3 integrins were used. RESULTS: A thin mural thrombus was seen at sites of denudation and plaque fracture (days 2 to 7). This provisional matrix was invaded by leukocytes (days 2 to 4) and alpha-actin-positive smooth muscle cells (SMCs; days 4 to 7). Thrombus was replaced by SMCs expressing hyaluronan and the associated versican proteoglycans (day 14). Versican was expressed throughout the neointima as it enlarged (day 28), but expression later subsided (day 112). Procollagen-I expression initially increased in the adventitia (day 4) and then in the forming neointima (day 14). Procollagen-I expression was found to persist within the adventitia and in the neointima in SMCs nearest the lumen (days 28 to 112). Elastin staining was prominent within the mature neointima (day 112) but not at earlier time points. Integrin expression also increased within the injured artery wall. alpha v beta 3 staining (fibrin[ogen] receptor) increased in the injured media (days 2 to 7) and was then seen throughout the early neointima (day 7). Low level expression of alpha V beta 3 subsequently persisted within the forming neointima (day 28). alpha 2 beta 1 (collagen receptor) expression increased in the neointima in SMCs nearest the lumen (day 28). CONCLUSIONS: Lumen narrowing after angioplasty in this model of atherosclerosis is caused largely by decreased artery wall diameter. The pattern of matrix and integrin expression within the injured artery wall is in many ways analogous to that of healing wounds. These observations suggest that tissue contraction may play a role in lumen narrowing at sites of arterial reconstruction. Strategies to inhibit wound contraction may prove effective in preventing restenosis.     

Prevalence of malnutrition in minors under 5 years of age in Tabasco

AIMS: Abdominal aortic aneurysms are characterised by changes in the extracellular matrix of the arterial media, in particular a reduction in elastin concentration. These changes are mediated by increased levels of endogenous matrix metalloproteinases (MMPs). Recently, calcium channel blockers have been shown to increase the proteolytic activity of MMP-2 secreted by vascular smooth muscle cells. It may therefore by hypothesised that calcium antagonists may potentiate the activity of MMPs in aneurysmal disease and thus accelerate AAA expansion. In this study, the ability of amlodipine--a calcium antagonist--to influence elastin degradation, was assessed in a previously described model of aneurysmal disease. METHODS: Porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 micrograms/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections. RESULTS: Gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p < 0.01) and this elevated activity was reflected in a significant destruction of medial elastin 27.0 vs. 40.5% (p < 0.05). CONCLUSION: Therapeutic ranges of amlodipine significantly enhanced elastin degradation and potentiated MMP-9 activity within the aortic organ cultures.     

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BACKGROUND: The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. RESULTS: In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.     

Effect of chronic dihydropyridine (isradipine) on the large arterial walls of spontaneously hypertensive rats

BACKGROUND: The effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30). METHODS AND RESULTS: Fifteen-week-old rats were randomly allocated to treatment with isradipine (3 mg/kg subcutaneously once a day) or to placebo and followed for 12 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were measured in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Histomorphometric parameters of the carotid and aortic media, including cross-sectional area, medial thickness, nucleus density and size, and medial contents of proteins of interstitial matrix, were measured by an automated morphometric system. Untreated SHRs had greater peripheral resistance, stiffer and thicker arterial walls because of smooth muscle cell hyperplasia (thoracic aorta and carotid artery) and/or hypertrophy (thoracic aorta), and increased collagen content than did normotensive control rats. SHRs showed a significant left ventricular hypertrophy. For the whole duration of treatment, treatment with CEB normalized the arterial pressure in SHRs. We observed a significant decrease in peripheral resistance, increased cardiac output, and left ventricular contractility without significant reduction in left ventricular hypertrophy. Increases in diuresis and natriuresis were associated during the last week of treatment in both treated strains with marked increase in plasma renin activity; in contrast, urinary aldosterone was increased by treatment in WKY rats but not in SHRs. Arterial compliance was significantly increased by CEB under control and passive conditions. CEB induced a significant reduction in the medial hypertrophy of the aortic walls of SHRs and WKY rats associated with a reduction in medial hyperplasia. In the carotid artery, CEB reduced smooth muscle cell hypertrophy but did not affect the smooth muscle cell hyperplasia. Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall. CONCLUSIONS: These results suggest that (1) despite normalization of arterial pressure, chronic treatment with CEB in SHRs does not significantly reduce left ventricular hypertrophy, probably because of increase in myocardial contractility and/or increase in plasma renin activity; (2) mechanical properties of the arterial wall are normalized by treatment; and (3) remodeling of the arterial wall by CEB is not uniform according to the studied vessel.     

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A pressure-driven flux of water occurs across the arterial wall in vivo. We have investigated the role of several interstitial components in determining the resistance of the wall to this flow. Pieces of porcine thoracic aorta were modified by thermal denaturation, enzymatic digestion or disruptive chemical treatments. The effect of these procedures on the wall content of glycosaminoglycans, collagen and elastin was determined by biochemical assay of uronic acid and hydroxyproline. Effects on hydraulic conductivity were measured by using a flow cell in which tissue was free to deform under applied pressure. Untreated tissue showed considerable variation in uronic acid content but conductivities were substantially less variable and averaged 0.75 x 10(-12) cm4/dyne.s. In tissue autoclaved for < 1 h, resistivity increased, possibly because interstitial components had been denatured but not removed from the wall. After longer periods, resistivity decreased by a factor of one hundred. More specific treatments showed that resistivity decreased by up to a factor of ten when glycosaminoglycans were removed and by a similar factor when collagen was removed. Tissue in which both were removed showed a hundred-fold decrease in resistivity. As with tissue subjected to prolonged autoclaving, the resistivity was still an order of magnitude higher than that of alkali- or acid-extracted elastin despite an apparently similar composition, suggesting the existence of a non-assayed component with important properties. The resistivity of the samples was decreased further by treatment with chymotrypsin, consistent with this component being microfibrillar protein.     

Nutritive value of hot water- or cocoa-pod ash solution-treated cocoa bean cake for broiler chicks

We recently reported on the immunolocalization of type II secretory nonpancreatic phospholipase A2 (snpPLA2) in human atherosclerotic lesions. In the present study, we present data on the distribution and ultrastructural localization of snpPLA2 in adjacent nonatherosclerotic and atherosclerotic regions of human arteries. Electron microscopy (EM) of immunogold labeling techniques with a monoclonal antibody was used to analyze arterial tissue. The human specimens analyzed were obtained from autopsy and surgery cases. The results with EM showed a stronger snpPLA2 immunoreactivity in regions of arteries with atherosclerotic lesions than in regions without lesions from the same individual. snpPLA2 immunoreactivity was stronger in the arterial intima of atherosclerotic than of nonatherosclerotic tissue. EM-immunogold examination revealed that the majority of snpPLA2 was localized along the extracellular matrix, associated with collagen fibers and other extracellular matrix structures. Intracellular snpPLA2 was observed in electron-dense vesicles in intimal cells. snpPLA2 was also found in contact with large, extracellular lipid droplets. These results support the hypothesis that extracellular snpPLA2 is localized at sites where it may hydrolyze phospholipids from lipoproteins and lipid aggregates retained in the extracellular matrix of the arterial wall. This may be a mechanism for in situ release of proinflammatory lipids, free fatty acids, and lysophosphatidylcholine in regions of apolipoprotein B accumulation, which are abundant in atherosclerotic lesions.     

An electron microscopic study of plasmatic arterionecrosis in the human cerebral arteries

An electron microscopic study of the intracerebral arteries from 9 hypertensive cases was performed in order to elucidate the morphogenesis of the plasmatic arterionecrosis which was considered to be the direct cause of hypertensive intracerebral hemorrhage. In the preceding stage of the arterial lesions, marked necrosis of medial smooth muscle cells and increase of basement membrane-like substance in the intima and media were observed. The lumina of these arteries were slightly dilated. The dilatation and hemodynamic factors were supposed to cause endothelial injury resulting in blood plasma insudation into the intima through the opened spaces between endothelial cells. The insudated blood plasma dispersed and dissolved the basement membrane-like substance, collagen and elastic fibers in the arterial wall, leading to the development of the plasmatic arterionecrosis.     

Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels

The effect of rapamycin (RPM) on the extent of arterial intimal thickening was determined in rat recipients of orthotopic femoral artery allografts or in rats that had undergone balloon catheter injury to carotid arteries. In untreated rats, neointima comprised approximately 50% of the arterial wall area in both models. Although treatment of allograft recipients for 40 days with 1.5 mg/kg/day RPM was ineffective, a dose of 6 mg/kg/day (days 0-7) followed by 3 mg/kg/day (days 8-39) reduced intimal thickening by 98% (P < 0.0001). The higher RPM dose reduced T cell and macrophage infiltration significantly and decreased the expression of IL-2 receptor, class II Ag, and mRNAs for growth factors and cytokines. Treatment with 1.5 mg/kg/day RPM (days 0-13) after balloon-catheter injury reduced intimal thickening by 45% (P = 0.0254) and substantially decreased macrophage infiltration and expression of class II Ag in the adventitia. Within the neointima, however, mRNAs for platelet-derived growth factor-alpha, basic fibroblast growth factor, and transforming growth factor-beta were still expressed. In summary, we have shown that RPM inhibits not only the vascular response to injury caused by allograft rejection, but also the response to balloon catheter injury. This new information is important to our understanding of: (1) the fundamental processes responsible for intimal thickening regardless of the cause of vascular injury, (2) mechanisms of action of RPM that explain its effects on the response to very different types of vascular injury, and (3) the potentially diverse therapeutic applications of drugs, like RPM, that inhibit the actions of both immune and nonimmune cytokines and growth factors.     

Accumulation of co-localised unesterified cholesterol and neutral lipids within vacuolised elastin fibres in athero-prone areas of the human aorta

To investigate whether there are alterations of elastin fibres in the arterial intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic aorta were taken soon after death from 13 healthy trauma victims whose ages ranged from 16 to 40 years. Two areas were compared: atherosclerosis-prone (AP) areas localised to the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas from the ventral aorta. Electron microscopic analysis combined with cytochemical staining was applied. Unesterified cholesterol was identified using the filipin-staining technique while neutral lipids were visualised by the OTO-technique. Intimal features were studied by combining the filipin-staining and the OTO-technique. Electron microscopical examination showed that in both AR and AP areas, some elastin fibres in the intima were vacuolised. Unesterified cholesterol was found to be predominantly localised in the musculoelastic layer, in particular, inside the vacuolised elastin fibres. This localisation was seen in all 13 AP areas studied in contrast to the AR areas where it was observed in only four of 13 aortas studied (P < 0.0005, chi2-test). Accumulation of neutral lipids inside vacuolised elastin fibres was found in five out of 13 AP areas but was not observed in any of the AR areas (P=0.01, chi2). A combination of the filipin-staining and OTO-techniques showed that some deposits of neutral lipids and unesterified cholesterol within vacuolised elastin fibres were independently located from each other, but more frequently, neutral lipids were co-located with unesterified cholesterol. The present observations indicate a difference between AP and AR intimal areas which, in particular, relates to the structure of elastin fibres in the musculoelastic layer. The observations suggest that alterations of the extracellular matrix are involved in the trapping and retention of cholesterol and neutral lipids within the intima at an early stage in the development of atherosclerotic lesions.     

The use of arterial allografts in aortic graft infections. A three year experience on eighteen patients

BACKGROUND: We describe our experience in the treatment of aortic graft infections by replacing them with arterial homografts as suggested by the good results recently described. METHODS: Between March 1994 and March 1997 eighteen patients with infections of the aortofemoral bifurcation segments have been treated. All patients underwent a complete explantation of the infected graft and an in situ revascularization with arterial homograft harvested in multiorgan removal. Eight segments were freshly preserved, 10 were cryopreserved. Four patients were operated as emergencies, of which 3 for aorto-enteric fistulas. All others presented a serious septic state. RESULTS: Three patients died in the early postoperative period: one of acute infarction and two of homograft related causes. In the follow-up there was only one death from acute infarction, a branch occlusion and two allograft enteric fistulas successfully treated by surgery. All surviving patients are submitted to periodical haemodynamic and tomographic control with an average follow-up of 22 months (range 3 months to 3 years) and there has been no allograft degeneration so far. CONCLUSIONS: The use of homologue arterial allografts has shown good results in the treatment of serious aortic graft infections resulting in adequate peripheral vascularization. There have been no significant degenerations to date, either in fresh or cryopreserved allografts.