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Biomedical subjects

A Pardo

Publications and source records attributed to A Pardo.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability.

Partial molal volumes (Vi infinity) of physostigmine, ranging from 232.9 to 239.8 cm3.mol-1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 degrees C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between Vi infinity and Xi. At solubility----0, Vi infinity----240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, Vi degrees (231.1), of physostigmine was lower than its lowest Vi infinity (value 232.9) in the series tested. Virtual cohesion parameters (lambda i) and excess free energies (delta EGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (-RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in lambda i over the invariant cohesion parameter, delta i (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between -RT In Xi and delta EGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA.

1-Propanol↗
PubMed1991

Production of platelet-derived growth factor by human lung cancer.

The production of platelet-derived growth factor (PDGF) was studied in small cell lung carcinoma, lung squamous carcinoma and lung adenocarcinoma cell lines, and in seven human lung tissues obtained from each type of lung cancer. By indirect immunofluorescence, PDGF was detected in all the cell lines. Likewise, five out of seven biopsies derived from patients with adenocarcinoma and squamous carcinoma, and four out of seven specimens with small cell carcinoma displayed a positive pattern for PDGF. In addition, lung carcinoma cell lines expressed both PDGF-A and PDGF-B/sis genes, as judged by Northern blot analysis. Biologically active, serum-free conditioned media obtained from all three cell lines stimulated the incorporation of [3H]thymidine into quiescent BALB/c-3T3 cells. This effect was abolished when IgG-PDGF antiserum was used. These findings suggest that an abnormal expression of PDGF occurs in the three more frequent types of lung cancer, which can play a potential role in neoplastic transformation and uncontrolled cell growth.

Adenocarcinoma↗
PubMed1991

Antiphospholipid antibodies in migraine.

We studied the presence of serum antiphospholipid antibodies (APA) in 35 patients with migraine and 75 controls. None of the controls showed APA, while we found these antibodies in five patients out of the 35 studied (p = 0.003). The clinical features of migraineurs with APA were similar to those of patients without them. After a follow-up of one to two years, no patient suffered any neurological complications or developed any clinical features that would suggest the presence of autoimmune disease. Our results suggest that APA are not prominent in the pathogenesis of migraine attacks, or significant in the course of otherwise healthy migraine patients.

Adult↗
PubMed1991

Thrombotic microangiopathic nephropathy in scleroderma and lupus anticoagulant.

A 47-year-old woman with overlap scleroderma-polymyositis syndrome and positive circulating lupus anticoagulant developed scleroderma nephropathy, characterized by rapidly progressive renal failure caused by thrombotic microangiopathy with widespread thrombi in small arteries and glomeruli. The possible relationship between lupus anticoagulant and the development of thrombosis at the small renal vessels level with the triggering of the scleroderma crisis is discussed.

Female↗
PubMed1991

Collagenase and collagenase inhibitors in bronchoalveolar lavage fluids.

Collagenase, collagenolytic activity and tissue inhibitor of metalloproteinases were evaluated in bronchoalveolar lavage from 25 patients with hypersensitivity pneumonitis and four control subjects. Patients were followed between two and three years, after which they were classified as "healed," "improved," or "worsened." In control samples, immunoreactive collagenase was not detected. The enzyme was present in four of seven patients who healed, six of ten patients who improved, and four of eight patients who worsened. There was no relationship between the presence or absence of BAL collagenase or its concentration and the evolution of the disease. Latent collagenolytic activity was detected only in 5 of the 14 patients who displayed immunoreactive collagenase. Regarding collagenase inhibitor, TIMP was present in BAL fluid from all patients and normal subjects. Although the highest values were found in two cases who healed or improved, there was not a statistically significant difference among the three groups of patients, neither between patients nor control subjects. These findings suggest that at least in HP, the presence of collagenase, collagenolytic activity, or TIMP in BAL fluid is not associated with the prognosis of the disease.

Adult↗
PubMed1991

Purification of a procollagenase-activator present in medium of cultured guinea pig carrageenin granuloma.

Activation of procollagenase constitutes a crucial event in collagenolytic activity regulation. In this study we have purified by DEAE-cellulose, Ultrogel AcA-44, and zinc chelate sepharose chromatographies, a procollagenase-activator from the culture medium of the guinea pig carrageenin granuloma model. On SDS-PAGE, the activator migrates as a principal band of Mr approximately 44,000. The molecule activates procollagenase from human lung fibroblasts in a concentration dependent manner and an enhancement of collagenase activity of trypsin-treated crude culture medium was observed. A loss of about 50% of its activity occurs after heating. In addition, this activator degrades gelatin and casein. All these data suggest that this procollagenase-activator might be stromelysin. The activator was found in both phases of the granuloma, at 7 days when collagen is actively deposited and an important proportion of the collagenolytic activity remains in latent form; and at 14 days, when this enzymatic activity is fully expressed.

Animals↗
PubMed1990

Percutaneous absorption of physostigmine: optimization of delivery from a binary solvent by thermodynamic control.

A series of binary vehicles was used to deliver physostigmine across dermatomed human skin. The vehicles consisted of isopropyl myristate (IPM) and isopropyl alcohol (IPA) mixed in various volume fractions. The kinetics of penetration is conveniently considered as the sum total of two contributing effects: a "push" process resulting from the excess free energy (delta EG) of the penetrant in the donor vehicle, and a "pull" process resulting from the effect of IPA and IPM on the skin barrier. The inverse ratio of the solubility of the drug in a given vehicle to that in pure IPA was used to estimate the relative delta EG, hence the relative "push" effect. The solubility of physostigmine was highest in pure IPA (delta = 11.5), lowest in pure IPM (delta = 8.5), and intermediate in their various mixtures. But the permeability coefficient (Kp) of physostigmine was highest when delivered from a 1:9 (v/v) solution of IPA:IPM and a calculated delta y = 8.8. A further increase in the volume fraction of IPA caused an opposite decrease in the Kp values of physostigmine. The "steady-state" flux (Jss) of IPA from the same vehicle was lowest at a volume fraction of 1:9 and highest at one of 1:1 IPA:IPM. Thus, the maximal physostigmine penetration enhancing effect of IPA occurs at the lowest flux of IPA found in the present series. This indicates that the "pull" process ascribed to the presence of IPA in the barrier membrane is not important enough to outweigh the decrease in delta EG of physostigmine following an increase in the volume fraction of IPA in the donor vehicle, or that an excess of IPA in the barrier is not conducive to further enhancement of physostigmine diffusivity across the barrier. Optimized percutaneous delivery of physostigmine is possible by thermodynamic control of the penetration process.

1-Propanol↗
PubMed1989

Lung collagenase inhibitors and spontaneous and latent collagenase activity in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis.

In order to analyze the mechanisms involved in the decreased collagenolytic activity previously observed in interstitial lung fibrosis, we studied the inhibitory collagenase activity and the latent activable collagenase in lung samples from five patients with IPF, six with HP, and three control subjects. Our results showed that in both diseases, the inhibitor levels were significantly higher than in control subjects. Findings suggest that in IPF low amounts of collagenase plus excessive enzyme-inhibitors may be operating to decrease collagen catabolism. In contrast, HP lungs seem to contain adequate amounts of the enzyme but higher levels of inhibitors play a role in the abnormal degradation observed in some patients.

Adult↗
PubMed1988

Enhanced electroretinogram in cats induced by exposure to mercury acetate.

The present study was undertaken in order to verify whether, and how, retinal functions are affected by subacute poisoning with organic mercury. Mercury acetate in various concentrations (0.025-0.25 mg/kg per day) was injected subcutaneously every second day to adult cats (N = 20) throughout a 2.5-4.0-week period. The electroretinogram (ERG) was recorded and the Hg2+ concentrations in the blood were determined. In nearly 90% of the intoxicated cats an enhanced electroretinogram (scotopic b-wave amplitude) was found as compared to its level in the normal control cats (N = 10). The latency of the ERG was found to be appropriately shorter, up to a maximal difference of nearly 20% in comparison to the controls. Hg2+ was present in the blood of the exposed cats during a 2.5-month period following the exposure. It is concluded that exposure to mercury acetate induces a permanent increase in the excitability level of the cat's retina.

Animals↗
PubMed1988

Allograft membranous glomerulonephritis and renal-vein thrombosis in a patient with a lupus anticoagulant factor.

A circulating lupus anticoagulant factor was detected in a 38-year-old man with end-stage renal disease and a 'lupus-like' syndrome with a diffuse proliferative glomerulonephritis. When treated with steroids, the 'lupus' complications were controlled and the anticoagulant factor disappeared; however, renal function did not recover and the patient commenced regular haemodialysis. Four months later the patient received a cadaver kidney transplant. At transplantation and during follow-up there was neither clinical nor laboratory evidence of lupus activity, but 19 months after transplantation, when steroids were tapered to a low dose, the lupus anticoagulant factor was detected, and renal-vein thrombosis complicated by sepsis led to the patient's death. A membranous glomerulonephritis was found on autopsy. This is the first time in which a (probably 'de novo') membranous glomerulonephritis has been detected in the allograft of a patient with circulating lupus anticoagulant factor.

Adult↗
PubMed1988

Lupus-like in vitro anticoagulant activity in end-stage renal disease.

Lupus-like anticoagulant is diagnosed by a prolonged activated plasma thromboplastin time not corrected after incubation with normal plasma, prolongation of diluted tissue thromboplastin time and of diluted Russel's viper venom time, excluding factor deficiencies or specific coagulation inhibitors. We studied the presence of this 'lupus-like anticoagulant' in 100 patients with end-stage renal disease, 56 on hemodialysis and 44 on conservative treatment. 'Lupus-like anticoagulant' activity was found in vitro in the blood of 22 patients (22%) being a significantly higher prevalence than that found in 125 patients with systemic lupus erythematosus (15%) and in 50 healthy controls (0%). Hemodialysis patients showed 'lupus-like anticoagulant' activity in 30% cases, compared to 11% patients on conservative treatment. The presence of 'lupus-like anticoagulant' was unrelated with primary disease or medication received. The incidence of thrombosis in patients with this in vitro anticoagulant was higher than in patients without it (23 vs. 13%), although this difference is not significant. We conclude that prevalence of 'lupus-like anticoagulant' is high in patients with end-stage renal disease, a previously unreported observation. Its clinical and pathogenetic significance should be studied further.

Adolescent↗