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Biomedical subjects

A Pardo

Publications and source records attributed to A Pardo.

At least 73 records · Page 4Linked to original sources
PubMed1996

Increased expression of intercellular adhesion molecule 1, CD11/CD18 cell surface adhesion glycoproteins and alpha 4 beta 1 integrin in a rat model of chronic interstitial lung fibrosis.

The expression of the intercellular adhesion molecule 1 (ICAM-1), and the integrins CD49, CD11b/c, and CD11a (LFA-1 alpha chain) was analyzed in an experimental model of pulmonary fibrosis. Adult rats were exposed to 75% oxygen during 10 weeks, and to 2.0 mg/kg of paraquat twice weekly. Rats were sacrificed at 2 days, and at 2 and 10 weeks after the first injection of paraquat. Lungs were fixed in 4% paraformaldehyde and used for histology and immunohistochemistry. At 2 days the lungs showed a diffuse inflammation composed of a mixed polymorphonuclear and mononuclear cell infiltrate. Afterwards, the inflammatory process was predominantly mononuclear, and an increasing fibroblast proliferation was observed. Early inflammatory events (48 h) correlated with a moderate increased expression of ICAM-1, LFA, and CD11b/c in epithelial cells as well as a pronounced expression of ICAM-1 and CD11b/c in macrophages. At 2 and 10 weeks, there was a progressive increased expression of CD11b/c and ICAM-1 by macrophages, as well as of LFA in epithelial cells, and of ICAM-1 and CD49 by epithelial and interstitial cells. Lymphocytes showed a slight increased expression of LFA at 2 weeks, and of CD49 at 2 and 10 weeks. These results suggest that macrophages expressing ICAM-1, CD11b/c, and CD49 are involved in the earlier and late phases of the disease whereas fibroblast and epithelial cells expressing ICAM-1 and CD49 might play a role in the cell interactions involved in the fibrotic phase.

Animals↗
PubMed1996

Increased expression of gelatinases and collagenase in rat lungs exposed to 100% oxygen.

Exposure of adult rats to 100% O2 produces a lethal injury by 72 h. We reasoned that matrix metalloproteinases participate in the pathogenesis of hyperoxic lung injury. To that end we studied the expression and activity of gelatinases A and B and interstitial collagenase in lung tissues and bronchoalveolar lavage fluids (BALF) of rats exposed to 100% oxygen for 60 h. Gelatin zymography of BALF samples revealed a 472 kDa molecular species both in controls and oxygen-exposed animals. In addition, BALF from hyperoxic rats exhibited a 95-kDa gelatinase. Likewise, BALF total gelatinolytic and collagenolytic activities were significantly increased in oxygen-exposed rats. In situ hybridization revealed an increase in type IV collagenases as well as interstitial collagenase mRNAs in the oxygen-exposed lungs. The three enzymes were expressed by alveolar macrophages, and in variable degrees by interstitial and alveolar epithelial cells. Immunoreactive gelatinase B and collagenase paralleled the cell localization of the mRNAs but were also detected in the alveolar walls and interstitium. In situ zymography showed gelatinolytic activity in frozen sections of oxygen-exposed lungs but not in normal lungs. The upregulation of these metalloproteinases during acute exposure to 100% O2 suggests that they might contribute to hyperoxic lung damage through the degradation of extracellular matrix components.

Animals↗
PubMed1996

Matrix metalloproteinases and lung injury.

The dynamic equilibrium of extracellular matrix (ECM) under different physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs), a family of structurally related zinc-dependent endopeptidases, are the physiological mediators of matrix remodeling. The expression and activity of these enzymes are highly regulated at several intra- and extracellular levels, so that in vivo enzymatic activity is the final result of a complex series of events including gene expression, zymogen activation, matrix binding, and enzymatic inhibition. MMPs are expressed at low levels in normal adult tissues, and their upregulation appears to play an important role in the development of a number of pathological processes. In acute lung injury, a disorder characterized by a severe disruption of the gas exchange alveolo-capillary structures, the upregulation of interstitial collagenase and gelatinases A and B strongly suggests that MMPs contribute to acute lung damage by facilitating the migration of inflammatory cells, as well as to the disruption of basement membrane components and extracellular matrix remodeling.

Extracellular Matrix↗
PubMed1996

Pathogenic mechanisms in the development of diffuse pulmonary fibrosis.

Diffuse pulmonary fibrosis is characterized by abnormal proliferation of mesenchymal cells, specifically fibroblasts and myofibroblasts, and by the accumulation of excessive amounts of matrix proteins, mainly collagens. The development of this pathological process is preceded by an inflammatory response, often dominated by macrophages and lymphocytes, which is mediated by the local release of chemoattractant factors, acting coordinately with an upregulation of cell-surface adhesion molecules. A subsequent persisting fibroproliferative reaction, in both interstitial and intraalveolar spaces, with progressive collagen accumulation distorts the lung architecture irreversibly. Excessive collagen deposition is the result of an imbalance in the collagen turnover rates characterized by a transient increase in collagen synthesis and a decrease in collagen degradation. Fibrosis is considered otherwise to be the final common pathway of a variety of lung disorders, and in this context, the diagnosis of pulmonary fibrosis implies the recognition of an advanced stage in the evolution of a complex process of abnormal repair.

Cell Division↗
PubMed1995

Fibroblasts isolated after fibrotic lung injury induce apoptosis of alveolar epithelial cells in vitro.

Primary lung fibroblasts were isolated from patients with idiopathic pulmonary fibrosis (HIPF), from normal human lung tissue (NH), from rats treated with 75% oxygen and paraquat (PA), and from normal adult rats (NR). Serum-free media conditioned by each fibroblast strain were tested on the human A549 cell line (HIPF and NH media) or on primary alveolar epithelial cells (AEC) isolated from normal adult rats (PA or NR media). Over 20-h incubation, HIPF- or PA-conditioned media induced DNA fragmentation and significant decreases in total recoverable DNA and cell number of A549 or AEC, respectively; NH or NR media had no significant effect relative to serum-free unconditioned media. Apoptosis of A549 and AEC was detected by altered nuclear morphology and was confirmed by terminal deoxynucleotidyl transferase-mediated bio-dUTP nick end labeling. The endonuclease inhibitors 10 microM aurintricarboxylic acid and 50 microM zinc inhibited HIPF-induced apoptosis of A549 cells by 68 and 71%, respectively. Both apoptosis and necrosis were induced by HIPF and PA media in a concentration-dependent manner. These results suggest that altered fibroblasts emerging during fibrotic lung injury release a soluble factor(s) capable of inducing cell death and net loss of AEC.

Animals↗
PubMed1995

Expression of a 2.8-kb PDGF-B/c-sis transcript and synthesis of PDGF-like protein by human lung fibroblasts.

The replication of fibroblasts is thought to be controlled by exogenous growth factors mainly secreted by macrophages and epithelial cells. However, under standard culture conditions, lung fibroblasts are able to produce several growth factors, suggesting an autocrine pathway of proliferation. In this work, we examined the expression of platelet-derived growth factor (PDGF-A) and PDGF-B-messenger RNA (mRNAs) by fibroblasts derived from four human adult normal lungs and from two fibrotic lungs. Northern blot analysis showed that both normal and idiopathic pulmonary fibrosis (IPF)-derived fibroblasts expressed a 2.8 PDGF-B/c-sis mRNA. This transcript was also observed as a minor form in human osteosarcoma cell line, used as control, which predominantly expressed a 4.0-kb PDGF-B mRNA. In two fibroblast cell lines, one fibrotic and one normal, the 4.0-kb transcript was also observed but was always weaker than the 2.8-kb mRNA. PDGF-A mRNA was not detected. By immunofluorescence, lung fibroblasts exhibited intracytoplasmic PDGF-like protein. Likewise, conditioned media from normal and IPF lung fibroblasts stimulated 3H-thymidine incorporation in BALB/c-3T3 cells that was significantly inhibited by anti-PDGF antibody. These results show that in vitro, some human lung fibroblasts express PDGF-B/c-sis mRNA, mainly an alternate 2.8-kb transcript, and produce PDGF-like protein.

Blotting, Northern↗
PubMed1994

Leukotriene C4 upregulates collagenase expression and synthesis in human lung fibroblasts.

Leukotriene C4 (LTC4), a mediator generated by a variety of inflammatory cells, participates in several physiological and pathological processes. It has been shown that LTC4 stimulates collagen synthesis by fibroblasts, suggesting a role in collagen turnover. However, the possible effect of this mediator on collagen degradation has not been examined. In this study we explored the role of LTC4 in the modulation of fibroblast interstitial collagenase and TIMP-1. Confluent cultures of three human normal lung fibroblast cell lines, and one derived from idiopathic pulmonary fibrosis (IPF) were exposed to LTC4 0.1, 1 and 10 nM, and to IL-1 beta as positive control. Collagenase and TIMP mRNAs expression were analyzed by Northern blot followed by densitometric scanning. Immunoreactive procollagenase was detected by immunoblot, and collagenase activity was measured using [3H]collagen. Our results showed that LTC4 enhanced several-fold collagenase mRNA expression in collagenase-producing fibroblasts, and induced the expression of the enzyme mRNA in collagenase-nonproducing fibroblasts, both in normal and IPF derived cell lines. LTC4 1 nM induced the highest response. Collagenolytic activity and immunoreactive collagenase paralleled collagenase mRNA expression. Interestingly, simultaneous exposure of fibroblasts to LTC4 plus IL-1 failed to show additive effects. Moreover, in two cell lines the combination resulted in a decrease of collagenase mRNA expression compared with both mediators separately. TIMP mRNA levels were not significantly modified by LTC4, nor IL1 beta. Our findings suggest that LTC4 plays a role in the modulation of fibroblast collagenase, and it may participate in extracellular matrix remodeling during lung inflammation.

Collagenases↗
PubMed1994

Cellular source of collagenase and TIMP-1 in carrageenin-induced granuloma.

We have examined the occurrence and cellular localization of interstitial collagenase and TIMP-1 mRNAs in a model of granuloma induced by carrageenin in guinea pigs. Granulomas were studied at 4, 7, 10, and 14 days after carrageenin injury using a combined protocol for in situ hybridization and immunofluorescence. Anti-vimentin monoclonal antibody was used to identify fibroblasts. Avidin-FITC and Texas red horse antimouse IgG were employed for detection of probes and antibody, respectively. Our results showed that during the extracellular matrix deposit phase (4 and 7 days), interstitial collagenase and TIMP-1 mRNAs were expressed only by fibroblasts as demonstrated by the colocalization of mRNA and vimentin. By contrast, during the initiation of the resorptive phase (10 and 14 days), fibroblasts and vimentin-negative cells, probably macrophages, expressed collagenase and TIMP-1. This study suggests that fibroblasts are the cell type expressing interstitial collagenase and TIMP-1 mRNA during all phases of the evolution of carrageenin granuloma and that macrophages, by contrast, express the mRNA for the enzyme and the inhibitor exclusively in the degradative phase.

Animals↗
PubMed1994

Proteolytic processing of von Willebrand factor subunit: heterogeneity in type-IIA von Willebrand disease.

Type IIA von Willebrand disease (vWD) is a heterogeneous disorder for which two different pathogenetic mechanisms have been proposed: increased proteolytic susceptibility of von Willebrand factor (vWF), and/or interference of its post-translational processing. Subunit analysis of vWF in type-IIA vWD has revealed an increased relative proportion of the 176- and 140-kDa subunit-derived fragments, suggesting an augmented fragmentation of vWF, even in the resting state. We analyzed the subunit pattern of vWF in plasma from five previously described patients with type-IIA vWD. All of them showed the above-mentioned pattern. In addition, the presence of a new band with an apparent molecular mass of 200 kDa, not described in normal individuals or in patients with vWD, was repeatedly observed in one of these patients. This patient also exhibited an abnormal vWF multimeric structure in platelets and in plasma, before and after desmopressin administration, when the blood was collected either in the presence or in the absence of proteinase inhibitors. We believe that an abnormal primary structure of vWF could be responsible for this abnormal proteolytic fragmentation pattern, as well as for the abnormal multimerization of vWF. Moreover, an abnormal susceptibility to proteolysis appears to be present, as suggested by the increase in the relative proportion of the 176-kDa fragment observed in the same patient. Future sequencing studies and genetic analysis may clarify whether there are one or two different defects related to the vWF of that patient. Our results indicate that the subunit analysis of vWF may reveal additional defects present in type-IIA vWD that may help our understanding of the pathogenesis of such disease.

Blood Platelets↗
PubMed1994

Prevalence of antiphospholipid antibodies in nephropathies not due to systemic lupus erythematosus.

Renal involvement by some types of thrombotic microangiopathy has been associated with the presence of antiphospholipid antibodies in both patients with systemic lupus erythematosus (SLE) and in those with other types of connective tissue disorders. To assess the prevalence and clinical significance of these antibodies in renal disease we prospectively studied anticardiolipin antibodies and lupus anticoagulant activity in 138 patients. These patients were classified into four groups: chronic glomerulonephritis (n = 57), acute and non-SLE systemic nephropathies (n = 13), non-immune-related nephropathies (n = 39), and SLE nephropathies (n = 29). The prevalence of antiphospholipid antibodies in patients with chronic primary glomerulonephritis (9%) was lower than in the SLE group (34%) and higher, but not significantly, than in patients with non-immunologically mediated renal diseases (2.6%). Positive patients in this group correspond to atypical "lupus-like" SLE forms or sporadic cases. In the group of patients with acute nephropathy and non-SLE systemic disorders, lupus anticoagulant was present in sic and anticardiolipin was present in four. In most cases the finding was transient and probably related to concomitant infection or active immune response. We conclude that there is a low prevalence of antiphospholipid antibodies in primary chronic glomerulonephritides, similar to that found in non-immunologically based nephropathies. The presence of these antibodies associated with chronic glomerulonephritis should raise the suspicion of SLE. On the other hand, positivity of these antibodies is a frequent finding in acute and systemic nephropathies. Therefore, the clinical and prognostic significance of their presence in these disorders should be further studied in a larger series of patients.

Adolescent↗
PubMed1994

Study of antiphospholipid antibodies in a patient with Sneddon's syndrome and her family.

BACKGROUND: Sneddon's syndrome is a disease characterized by livedo reticularis and cerebrovascular lesions, with a hereditary transmission and unknown etiopathogenesis. A number of reports have documented a link between antiphospholipid antibodies and Sneddon's syndrome with different results. The present work was designed to sequentially study antiphospholipid antibodies in a patient with Sneddon's syndrome and her family and their potential role in thrombotic events. We used cardiolipin and a mixture of phospholipids from rabbit brain as antigen for antiphospholipid assays to determine diagnostic usefulness. CASE DESCRIPTIONS: A patient with Sneddon's syndrome and 12 available family members belonging to three generations were evaluated to determine the presence of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) during vascular thrombotic events and asymptomatic periods. CONCLUSIONS: Our results support a temporal relation between thrombotic events in Sneddon's syndrome and lupus anticoagulant; anticardiolipin antibodies remained invariable. Our index case patient and her father could be diagnosed as having primary antiphospholipid antibody syndrome. Aspirin was not effective in preventing thrombosis. After the onset of oral anticoagulant therapy, no recurrences were seen. The use of a mixture of phospholipids as antigen could present some advantages in serological studies performed in antiphospholipid syndromes.

Adolescent↗
PubMed1994

[Checking oral anticoagulation in capillary blood].

PURPOSE: To check out the reproducibility and costs of prothrombin time (PT) determination as a control of oral anticoagulant therapy (OAT) in plasma and capillary blood. PATIENTS AND METHODS: The study was carried out in two phases: along two years, 1,700 patients with OAT were controlled, 700 of them in the hospital outpatient clinic. In 149 patients INR was simultaneously determined in both capillary and venous blood. The 700 patients receiving acenocoumarin who had been controlled in 1991 according to the conventional plasma-sample fashion, were controlled in the second year (i.e., 1992) by means of capillary blood testing, a comparison of the costs of each method and the need for anticoagulant drugs being undertaken. Venous blood PT was assessed with reagent thromboplastin (Tromborel S) in an Electra-1000 (MLA) system. An automated Trombotrack system was used for the capillary blood tests using Thrombotest as current procedure. The results were expressed as INR in both methods. The statistical evaluation of the results was carried out by means of Student's t, variance analysis, and correlation study. RESULTS: No significant differences were found in the anticoagulation intervals attained from venous or capillary blood samples. No significant differences were seen in 87 patients on whom the test was repeated in two samples drawn from a single capillary puncture. The weekly OAT doses of 30 patients along six months were analysed. The need for anticoagulant drugs was similar (17.4 vs 17.2 mg/patient/week). The mean INR in 1991 was 2.82 and the mean drug-need was 15.24 mg/week, whereas in 1992 the mean INR was 2.86 and the need for anticoagulant was 15.49 mg/week. The costs of the conventional method were 103.6 Pta, this being 70 Pta for capillary blood, which means a 32% savings. CONCLUSIONS: OAT control by means of PT performed on capillary blood must be considered a substitutive method for the venous blood assay due to its efficacy, simplicity and lower costs.

Acenocoumarol↗
PubMed1993

[Dyslipemia and HIV-1 infection in intravenous drug addicts].

BACKGROUND: It has been demonstrated that hypertriglyceridemia and hypocholesterolemia are frequent signs in homosexual patients with AIDS. Lipid abnormalities of the intravenous drug addict (IVDA) however, and its relation with infection by the human immunodeficiency virus (HIV) have not been sufficiently studied. METHODS: Four hundred thirty-five consecutive patients attended for infectious complications or for carrying out detoxication treatment were studied. Demographic (age, sex), anthropometric (weight, height), use of intravenous drugs (principal drug used, time of addiction) and analytic data (HIV-1 antibodies, total lymphocytes, CD4+ lymphocytes, serum albumin, total cholesterol, plasma triglycerides and transferrinemia) were collected. RESULTS: The age of the patients was found to be between 15-44 years of age. Ninety-five percent were heroin addicts with a time of addiction greater than 4 years. Those who were HIV-1 positive had been drug users for a longer period of time (p < 0.01), had less weight (p < 0.01), lower albuminemia (p < 0.05) and cholesterolemia (p < 0.01), as well as a lower number of CD4+ lymphocytes (p < 0.01). No differences were observed with regard to age, transferrinemia and plasma triglyceride concentration. The prevalence of hypertriglyceridemia (> 1.97 mmol/l; 175 mg/dl) was of 18% for the IVDA with HIV-1 infection and 23% for seronegative individuals (p = 0.3). Hypercholesterolemia was significantly more prevalent in HIV-1 positive individuals (20%) than in the seronegative subjects (9%) (p < 0.01). In the HIV-1 positive patients, most of whom where asymptomatic, a decrease in total cholesterol and an increase in plasma triglycerides was observed according to the decrease in the number of CD4+ lymphocytes. CONCLUSIONS: Infection by the human immunodeficiency virus is accompanied by an increase in plasma triglycerides and a decrease of total cholesterol in relation with the alteration of cellular immunity. However, heroin addicts present some differential characteristics similar to those of chronic alcoholics, poor diet, anorexia induced by opioids, autoimmunity phenomena and recurrent infections throughout drug addiction which may justify lipid abnormalities of multifactorial origin.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Comparison between lung parenchyma and bronchoalveolar lavage collagenolytic activity.

We have evaluated, in an experimental model of silicosis in guinea pigs, if the presence of collagenolytic activity in bronchoalveolar lavage (BAL) fluid reflects the collagen catabolism in lung parenchyma. We measured simultaneously BAL collagenase activity, using as substrate [3H]type I collagen, and lung collagenolytic activity by the tissue pellet assay. Animals (n = 30) were instilled intratracheally with 50 mg of quartz DQ-12 and sacrificed 15, 30, and 60 days after silica administration. Guinea pigs instilled with saline solution were used as controls. Our results showed that lung parenchymal collagenolytic activity was present in all experimental and normal guinea pigs. There were no statistical differences between silicotic and normal animals at 15 and 30 days. At 60 days, however, a significant decrease in tissue collagenolytic activity was observed in silicotic animals (161 +/- 100 vs. 400 +/- 152 units of collagenase activity; p < 0.001). In contrast, BAL collagenolytic activity was revealed only in 7 of 10 silicotic animals at 15 days and 30 days, and in 4 of 10 at 60 days. Normal guinea pigs did not exhibit BAL collagenase activity. BAL and tissue collagenase activity from each experimental animal were analyzed by straight line regression and no significant relationship was observed (r = 0.082; p = 0.87). This suggests that BAL collagenolytic activity does not reflect lung tissue collagen turnover.

Animals↗
PubMed1992

Kinetics of transdermal penetration of an organic ion pair: physostigmine salicylate.

Physostigmine salicylate was delivered from a series of solvents consisting of isopropyl myristate, isopropyl alcohol (IPA), and their mixtures across dermatomed human skin. The apparent steady-state fluxes over the time range of the test, obtained separately for physostigmine and its corresponding salicylate, indicate a consistent trend toward higher values for the salicylate in the series tested. The ratios of salicylate fluxes to physostigmine fluxes ranged from 1.1 to 3.34, the higher ratios being obtained at a volume fraction of IPA exceeding 0.7. Ionization of the ion pair at the pH of the hydrated stratum corneum immediately after its partitioning into the membrane, followed by differential diffusion of the species across the membrane, is consistent with the kinetics of penetration. It is proposed that the apparent volume of distribution of physostigmine is larger than that of salicylate and, hence, a smaller concentration difference across the diffusion barrier exists for physostigmine. This hypothesis can explain the lower flux of physostigmine to conform to Fick's first law of diffusion and the assumption of equal molar transfer to the skin of both species. The hypothesis implies that if steady state appears to have been reached for the faster migrating salicylate over the time range tested then the apparent steady state of physostigmine is not a true one. Increasing the salicylate content in one of the donor solutions by eight times over that of physostigmine decreased the saturation concentration of physostigmine but not in its flux. Increasing the physostigmine content by 6.5 times over that of salicylate in the same donor solution did not change either the flux or the salicylate concentration but decreased the permeability coefficient of physostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Production of collagenase and tissue inhibitor of metalloproteinases by fibroblasts derived from normal and fibrotic human lungs.

Several experiments have demonstrated low collagenolytic activity during the development of pulmonary fibrosis. In order to determine if fibroblasts play a role in this alteration, procollagenase and tissue inhibitor of metalloproteinases (TIMP) were quantified in fibroblasts derived from 12 human lung specimens (normal = 6, idiopathic pulmonary fibrosis [IPF] = 6). Under basal conditions, three cell strains from normal and three from fibrotic lung specimens did not synthesize collagenase and a similar number of normal and IPF-derived fibroblast strains produced the enzyme. However, the rate of enzyme synthesis among normal and fibrotic collagenase producing fibroblasts exhibited significant differences. Thus, whereas normal fibroblasts produced more than 300 ng/ml, fibrotic lung fibroblasts secreted approximately half of this amount (115 +/- 67 ng/ml). Phorbol myristate acetate (PMA) enhanced collagenase production in all of the 12 lung fibroblast lines tested. In four IPF fibroblasts, PMA increased collagenase secretion close to those of normal stimulated lung fibroblasts; however, a lower induction was observed in cell strains from two fibrotic lung specimens. There was a wide variation in TIMP production both in normal and fibrotic lung fibroblasts, and no statistically significant difference was observed. Under basal conditions, TIMP levels ranged from 329 to 16,911 ng/ml in normal lung cells, and from 377 to 17,557 in fibrotic lung fibroblasts. PMA induced a severalfold increase in all cell lines. These results suggest that there are subpopulations of lung fibroblasts with different potential to produce collagenase and TIMP in vitro, and that the predominance of low collagenase-producing subsets may contribute to the development of fibrosis.

Adult↗
PubMed1992

Collagenase-inhibitory activity in deposit and resorption phases of guinea pig carrageenin granuloma.

The levels of collagenase inhibitor, both free and bound to metalloproteinases, were evaluated at 7 days [deposit phase (DP)] and 14 days [resorptive phase (RP)] of evolution of the subcutaneous carrageenin-induced granuloma in the guinea pig. The level of free collagenase inhibitor was considerably higher in the supernatant of DP granulomas (7.95 +/- 1.53 U/mg protein) as compared to that of RP granulomas (2.53 +/- 0.41 U/mg protein). When the samples were heated at acid pH to release the inhibitor from metalloproteinase-inhibitor complexes, free inhibitor was recovered in both phases. However, the units of recovered collagenase inhibitor were several fold higher in all RP granulomas in comparison with DP granulomas (6.88 +/- 2.46 vs 1.5 +/- 0.53). Therefore, DP and RP tissues exhibited similar total amount of tissue inhibitor. By HPLC, collagenase inhibitor activity was localized in a fraction consistent with the size of TIMP. These results suggest a different balance of collagenase and collagenase inhibitor during the evolution of the granuloma; an excess of inhibitor over metalloproteinases appears to predominate during the phase of collagen accumulation contrasting with an inverse situation when the granuloma is healing.

Animals↗