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Biomedical subjects

E González

Publications and source records attributed to E González.

At least 19 recordsLinked to original sources
PubMed1996

Endothelin-1 induces loss of proteoglycans and enhances fibronectin and collagen production in cultured rabbit synovial cells.

Endothelin-1 exerts a wide range of biological actions besides its characteristic vasoconstrictor function. The potential participation of endothelin-1 in rheumatic diseases has hardly been explored. We have studied the possible role of endothelin-1 as a modulator of extracellular matrix turnover in cultured rabbit synoviocytes. In relation to basal levels, endothelin-1 increased the mRNA levels of collagen I and fibronectin at 24 h (130 +/- 9% and 132 +/- 18%, respectively), but did not modify the expression of decorin core proteoglycan. Endothelin-1 also decreased proteoglycan metabolism (about 50% of proteoglycan synthesis inhibition and 270 +/- 32% of degradation rate vs. basal, P < 0.05 in both cases) and enhanced total collagen (1.5 +/- 0.5 vs. 0.8 +/- 0.2 microgram hydroxyproline/microgram DNA in basal, P < 0.05) and fibronectin protein synthesis (157 +/- 14% of [35S] methionine incorporation vs. basal, P < 0.05). The endothelin ETA receptor antagonist BQ-123 (Cyclo D-trp-D-asp-pro-D-val-leu) displaced [125I]endothelin-1 binding and inhibited endothelin-1 effects on extracellular matrix components. The cell incubation with indomethacin totally reversed the endothelin-1 effect. These data suggest that endothelin-1 may be an important mediator of the pathogenesis of joint damage, disturbing the extracellular synovial matrix turnover through the endothelin ETA receptors.

Animals↗
PubMed1996

Anti-inflammatory effect of a PAF receptor antagonist and a new molecule with antiproteinase activity in an experimental model of acute urate crystal arthritis.

Platelet activating factor (PAF) is a potent mediator of allergic and inflammatory reactions in different pathological conditions. During recent years there has been increasing evidence that PAF can play an important role in the pathogenesis of arthritis. The PMN proteinases make an important contribution to the final tissue joint destruction in arthritis. In a rabbit model of acute crystal arthritis, we have compared the anti-inflammatory effect of two new molecules: BN 50727 with anti-PAF activity, and BN 50548 an inhibitor of PMN proteinases. These molecules were administered dissolved in DMSO at doses of 6 mg/kg three times daily i.p., beginning 24 h before the induction of arthritis. Compared with the untreated animals those receiving the drugs, presented a significant diminution in: (1) the synovial fluid volume; (2) the amount of cells infiltrating the joint cavity and the synovial membrane; and (3) the PGE2 concentration. Furthermore, in both groups of treated rabbits there was a significant decrease in synovial IL-6 concentration and in C-reactive protein serum levels and an important decline of histopathological score. The treatment with BN 50548 induced a significant reduction of TNF levels in the synovial fluid vs DMSO-treated and untreated rabbits. These results further strengthen that in an acute experimental arthritis model, molecules with capacity to antagonize the in vivo action of PAF have an anti-inflammatory effect reflecting an important role for this mediator in the pathogenesis of arthritis. We have also seen that an inhibitor of proteinases is capable of improving the joint inflammation apparently through a decrease in tumor necrosis factor (TNF) and interleukin-6 (IL-6) synovial levels. Furthermore, the proteinase inhibitor treatment preserves the loss of articular proteoglycan content, in an acute arthritis model. In conclusion, BN 50727 and BN 50548, two compounds with PAF antagonist and antiproteinase activity, respectively exert an anti-inflammatory effect in an experimental model of acute urate crystal arthritis, probably due to a decrease in TNF alpha and IL-6 synthesis.

Acute Disease↗
PubMed1996

Treatment of pyogenic granulomas with the 585 nm pulsed dye laser.

BACKGROUND: Current therapeutic alternatives for pyogenic granulomas include surgical excision, electrodesiccation and curettage, cryotherapy, and ablation with CO2 or continuous-wave vascular lasers. OBJECTIVE: Our purpose was to investigate the use of the 585 nm flashlamp-pumped pulsed dye laser (585 nm PDL) for the treatment of pyogenic granulomas in terms of efficacy, advantages in technique, and side effects. METHODS: Eighteen patients with symptomatic pyogenic granulomas in a variety of locations were treated with the 585 nm PDL and examined. RESULTS: Sixteen of 18 treated patients demonstrated both symptomatic and clinical clearing of the lesions with excellent cosmetic results after treatment. The two patients who dropped out after one to two 585 nm PDL treatments were eventually treated successfully with electrodesiccation and curettage. No postoperative complications and no persistent pigmentary changes or scarring were observed. The procedure required no anesthesia, and postoperative care was limited to the application of a topical antibiotic ointment. CONCLUSION: Our experience suggests that treatment of pyogenic granulomas with the 585 nm PDL is a safe, effective, and reasonable alternative to conventional therapy.

Administration, Cutaneous↗
PubMed1996

Urinary excretion of platelet-activating factor in human and experimental nephrosis.

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid that has been implicated in the pathogenesis of glomerulonephritis and can be synthesized by glomerular cells in response to different stimuli. PAF increases glomerular permeability to proteins and urinary PAF has been determined to be of renal origin. In order to assess whether urinary PAF can be found augmented in situations of glomerular damage without glomerular leukocyte infiltration, urinary PAF was quantified in human and experimental nephrosis. METHODS: Urinary PAF was quantified by platelet bioassay and glomerular PAF by incorporation of 3H-acetate into PAF. PAF was characterized by its behaviour on thin-layer chromatography and high performance liquid chromatography and the blockade of its bioactivity by receptor antagonists. RESULTS: Urinary PAF excretion was significantly higher in patients with active idiopathic nephrotic syndrome than in controls (5.8+/-1.5 versus 1.7+/-0.75 mg/24 h; P<0.05) and patients in remission (1.63+/-0.75 ng/24 h; P<0.02). In rats with nephrosis induced by puromycin aminonucleoside there was an early increase in urinary PAF excretion (138+/-19 versus 49+/-22 pg/24 h in controls; P<0.035) that coincided with the augmented glomerular PAF synthesis (67+/-3.4 versus 36+/-1.2 DPM/mg protein in controls; P<0.003). CONCLUSIONS: These results suggest that the synthesis of PAF in the kidney may be involved in the pathogenesis of the proteinuria in idiopathic nephrotic syndrome and that urinary PAF excretion may be a good marker of disease activity.

Animals↗
PubMed1996

Effects and interactions of endothelin-1 and angiotensin II on matrix protein expression and synthesis and mesangial cell growth.

Mesangial cell growth and accumulation of extracellular matrix proteins constitute key features of progressive glomerular injury. Endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictor agents, evoke a number of similar responses in mesangial cells. In rat mesangial cells, we compared ET-1 and Ang II effects on matrix protein production and cell proliferation as well as the potential interaction between the two hormones. When cells in 0.5% fetal calf serum were incubated for 24 hours with various concentrations of ET-1 or Ang II, both peptides stimulated, in a dose-dependent manner, fibronectin and type IV collagen mRNA expression, fibronectin synthesis, and mitogenesis. Incubation with specific receptor antagonists of both hormones demonstrated that endothelin subtype A (ETA) and angiotensin type 1 (AT1) receptors were involved. Preincubation of cells with two different protein kinase C inhibitors or with a neutralizing anti-transforming growth factor-beta antibody, but not an unrelated IgG, diminished the peptide-induced fibronectin synthesis. A dual interrelation seems to exist between ET-1 and Ang II. Thus, the AT1 receptor antagonist losartan and the angiotensin-converting enzyme inhibitors quinaprilat and captopril diminished the ET-1-mediated effects, whereas, the ETA receptor antagonist BQ-123 diminished the Ang II-induced fibronectin synthesis and mesangial cell proliferation. Our results suggest that ET-1 and Ang II stimulate matrix protein synthesis and mesangial cell mitogenesis through ETA and AT1 receptors, respectively, by complicated mechanisms, implicating protein kinase C activation, synthesis of transforming growth factor-beta, and release of one peptide by the other. These data could be important for a better understanding of the participation of vasoactive substances in the pathogenesis of glomerulosclerosis.

Angiotensin II↗
PubMed1996

Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis.

Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis.

Animals↗
PubMed1995

The proximal straight tubule (PST) basolateral cell membrane water channel: selectivity characteristics.

Proximal straight tubules (PST) were dissected from rabbit kidneys, held by crimping pipettes in a chamber and bathed in a buffered isosmotic (295 mOsm/kg) solution containing 200 mM mannitol (MBS). Changes in tubule diameter were monitored on line with an inverted microscope, TV camera and image processor. The PST were then challenged for 20 sec with MBS made 35 mOsm/kg hyperosmotic by addition of either NaCl, KCl, mannitol (M), glycerol (G), ethylene glycol (E), glycine (g), urea (U), acetamide (A) or formamide (F). With NaCl, KCl, M, G, E, g, U, and A, tubules shrunk osmometrically within 0.5 sec and remained shrunk for as long as 20 sec without recovering their original volume (sometimes A showed some recovery). PST barely shrunk with F and quickly recovered their original volume. The permeability coefficients were 0 microns/sec (NaCl, M, g, E and U), 1 micron/sec (A), 84 microns/sec (F) and 0.02 micron/sec (G). The reflection coefficients sigma = 1.0 (NaCl, KCl, M, G, E, g and U), 0.95 (A) and 0.62 (F). Similar sigma values were obtained by substituting 200 mOsm/kg M in MBS by either NaCl, KCl, G, E, g, U, a or F. The olive oil/water partition coefficients are 5 (M), 15 (U), 85 (A) and 75 (F) (all x 10(-5)). Thus, part of F permeates the cell membrane through the lipid bilayer. The probing molecules van der Waals diameters are 7.4 x 8.2 x 12.0 (M), 3.6 x 5.2 x 5.4 (U), 3.8 x 5.2 x 5.4 (A) and (3.4 x 4.5 x 5.4 (F) A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The paracellular channel for water secretion in the upper segment of the Malpighian tubule of Rhodnius prolixus.

Lumen to bath J12/C1 and bath to lumen J21/C2 fluxes per unit concentration of 19 probes with diameters (dm) ranging from 3.0-30.0 A (water, urea, erythritol, mannitol, sucrose, raffinose and 13 dextrans with dm 9.1-30.0 A) were measured during volume secretion (Jv) in the upper segment of the Malpighian Tubule of Rhodnius by perfusing lumen and bath with 14C or 3H-labeled probes. Jnet = (J12/C1-J21/C2) was studied as a function of Jv.Jv was varied by using different concentrations of 5-hydroxy tryptamine. Jnet for 3H-water was not different from Jv. We found: (i) A strong correlation between Jnet and Jv for 8 probes dm = 3.0-11.8 A (group a probes), indicating that the convective component of Jnet is more important than its diffusive component and than unstirred layers effects which are negligible. Therefore group a probes are solvent dragged as they cross the epithelium. (ii) There is no correlation between Jnet and Jv for 11 probes with dm = 11.8-30 A (group b). Therefore these probes must cross the epithelium by diffusion and not by solvent drag. (iii) In a plot of Jnet/Jv vs. dm group a probes show a steep linear relation with a slope = -0.111, while for group b probes the slope is -0.002. Thus there is a break between groups a and b in this plot. We tried to fit the data with models for restricted diffusion and convention through cylindrical or parallel slit pathways. We conclude that (i) group a probes are dragged by water through an 11.0 A-wide slit. (ii) Most of Jv must follow an extracellular noncytosolic pathway. (iii) Group b probes must diffuse through a 42 A-wide slit. (iv) A cylindrical pathway does not fit the data.

Animals↗
PubMed1995

Inhibition by Cl- channel blockers of the volume-activated, diffusional mechanism of inositol transport in primary astrocytes in culture.

[3H]Inositol accumulated by rat brain cultured astrocytes is released when cells swell by exposure to solutions of decreased osmolarity. Activation of inositol efflux was proportional to reductions in osmolarity from 30%-70%. This volume-activated inositol efflux pathway was increased (27%) in Na(+)-free medium and decreased (22%) in Cl(-)-free medium. It was independent of extracellular Ca2+ and was reduced (30%) in the presence of the intracellular chelator [1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester] (BAPTA-AM). The inositol efflux pathway was markedly inhibited by Cl- channel blockers, which at maximal inhibitory concentrations decreased inositol efflux by 70%-83%. The potency range of the drugs was: 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) > 1-9, dideoxyforskolin > 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS) > niflumic acid. Inositol efflux was strongly inhibited by the SH blocker N-ethyl maleimide (NEM), which at 100 microM abolished inositol release. Inositol efflux can be reversed by increasing its extracellular concentration, suggesting that the efflux is mediated by a diffusional pathway whose direction is given by the concentration gradient. The inhibition of volume-associated fluxes of inositol by Cl- channel blockers supports the suggestion of an anion channel as the common pathway for inorganic and organic osmolytes in cultured astrocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Additional dolabellane diterpenes from the Caribbean gorgonian octocoral Eunicea laciniata.

The Caribbean gorgonian octocoral Eunicea laciniata from the coasts of Palomino Island, Puerto Rico, has yielded four known and five new diterpenes based on the dolabellane ring system. The structures of the novel compounds 3-7 were established by interpretation of their spectral data. Some of these new compounds showed weak cytotoxicity against HeLa cells.

Animals↗
PubMed1995

ACE inhibition reduces proteinuria, glomerular lesions and extracellular matrix production in a normotensive rat model of immune complex nephritis.

We studied the effect of the angiotensin converting enzyme (ACE) inhibitor, quinapril, on the clinical and morphological lesions of a normotensive model of immune complex nephritis. Untreated rats developed massive nephrotic syndrome, intense cell proliferation and glomerular and tubulointerstitial lesions. In the renal cortex of nephritic rats there was a significant increase in gene expression of TGF-beta 1, fibronectin and collagens, and ACE activity. Systolic blood pressure remained normal with progression of the disease. Administration of quinapril for three weeks to animals with glomerular lesions (proteinuria 20 to 50 mg/day) avoided the development of intense proteinuria (79 +/- 28 vs. 589 +/- 73 mg/day, P < 0.001) and decreased cell proliferation, glomerulosclerosis, tubulointerstitial lesions, and inflammatory infiltrates. Cortical gene expression of TGF-beta 1 and matrix proteins was also diminished. ACE activity was inhibited by 68% in renal cortex. These results show that quinapril administration to normotensive rats with immune complex nephritis decreases proteinuria and glomerular and tubulointerstitial lesions, probably modulating the local angiotensin II generation and its effects on cell growth, TGF beta and matrix protein synthesis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators and proteoglycans in experimental nephrosis.

Nephrosis is characterized by glomerular epithelial cell injury and a decrease in the glomerular basement membrane (GBM) proteoglycan content. Although CsA is a useful treatment for a group of patients with this disease, its mechanism of action is unclear. We have previously shown that in experimental nephrosis there is an increase in the glomerular production of tumour necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF). Here we have studied the effect of CsA on kidney generation of TNF-alpha and PAF in puromycin aminonucleoside (PAN) nephrosis as well as on the synthesis of proteoglycans by cultured glomerular epithelial cells. Rats receiving CsA had, on day 8 of PAN injection, a significant reduction in proteinuria, blood cholesterol levels and in interstitial mononuclear cells. A diminution in glomerular production and urinary excretion of TNF-alpha and PAF was also noted. In in vitro studies, at 24 h of incubation PAF and TNF-alpha induced in glomerular epithelial cells a significant decrease in proteoglycan synthesis. Neither PAF nor TNF-alpha had any significant effect on glomerular epithelial cell proliferation. CsA alone induced a dose-response increase in proteoglycan synthesis and a slight decrease in cell proliferation. CsA also reversed the inhibitory effect of PAF and TNF-alpha on proteoglycan synthesis. However, CsA did not alter the pattern of proteoglycan production, remaining around 50% chondroitinase ABC-, 15% heparitinase-sensitive. Our results indicate that PAF and TNF-alpha could be implicated in the pathogenesis of nephrosis through the inhibition of proteoglycan synthesis by glomerular epithelial cells. The beneficial effect of CsA in nephrosis may be due to the recovery of the GBM charge selectivity caused by the normalization of glomerular PAF and TNF-alpha synthesis and the increase in proteoglycan synthesis by glomerular epithelial cells.

Animals↗
PubMed1995

IL-1 beta and IL-6 stimulate the production of platelet-activating factor (PAF) by cultured rabbit synovial cells.

The aim of this study was to determine whether synovial cells are capable of producing PAF in the presence of cytokines such as IL-1 beta and IL-6 and other stimuli. Synovial cells were obtained from joints of healthy rabbits. PAF production was assayed by measurement of serotonin release in rabbit platelets and the incorporation of 3H-acetate into PAF. Synovial cells produced PAF after 5 min of incubation with ionophore A23187, reaching the maximal amount at 15 min (4.3 +/- 0.7 x 10(-3) pmol of PAF/mg protein, P < 0.005, n = 4), and declining afterwards. The treatment of synoviocytes with IL-1 beta and IL-6 induced synthesis of PAF after 5 min of stimulation, reaching the greatest production at 15 min with IL-6 and 30 min with IL-1 beta (3.6 +/- 1.1 x 10(-3) and 3.3 +/- 1.2 pmol of PAF/mg protein, respectively, P < 0.05, n = 4). The incubation of the cells with PMSF, an inhibitor of acetylhydrolase, before the addition of the stimuli, increased the incorporation rate of 3H-acetate, suggesting a rapid degradation of PAF by synoviocytes. These results demonstrate that synovial cells can produce PAF after stimulation with agonists, such as ionophore, and cytokines. Thus, PAF, acting alone or with other mediators, could amplify the inflammatory joint reaction.

Animals↗
PubMed1995

Fibronectin (FN) decreases glomerular lesions and synthesis of tumour necrosis factor-alpha (TNF-alpha), platelet-activating factor (PAF) and FN in proliferative glomerulonephritis.

We have studied the effect of therapy with plasma FN on glomerular synthesis of PAF, TNF-alpha and FN, in experimental proliferative glomerulonephritis. Glomerular PAF, TNF-alpha and FN production were increased in rats with nephritis. Peak glomerular PAF production preceded, while peak glomerular TNF-alpha bioactivity coincided with maximal proteinuria. Rats treated with FN (5 mg/kg per 48 h) for 15 days had less proteinuria, glomerular and interstitial cell infiltration and glomerular PAF, TNF-alpha and FN synthesis than non-treated rats. In order to characterize further the mechanisms of action of FN, healthy rats were injected with either FN or saline. Peripheral blood mononuclear cells and neutrophils from healthy rats injected with FN secreted less TNF-alpha and PAF, respectively, than those obtained from saline-treated rats. Our data suggest that the beneficial effect of FN may be related to decreased number of glomerular leucocytes and decreased synthesis of inflammatory mediators and extracellular matrix.

Animals↗
PubMed1995

Involvement of tumor necrosis factor-alpha in the pathogenesis of experimental and human glomerulonephritis.

The evidence supporting a role for TNF-alpha in glomerular diseases can be summarized with the following: TNF-alpha can be secreted in the kidney by intrinsic renal cells and infiltrating phagocytes, as has been shown in vitro and in vivo during glomerular injury. TNF-alpha has proinflammatory actions which include cell death, chemotactic properties, and modulation of secretion of other inflammatory mediators, and extracellular matrix (Fig 5). Administration of exogenous TNF-alpha or agents that induce release of endogenous TNF alpha, such as endotoxin, increase the severity of experimental glomerular injury. Furthermore, the blockade of TNF-alpha action with specific antibodies, soluble receptors, or inhibitors improves the outcome of glomerulonephritis. Finally, several of the agents currently in use for the therapy of glomerular injury, such as corticosteroids and cyclosporine, are known to modulate the production of TNF-alpha. Specific TNF-alpha antagonists or inhibitors may have a role in the management of glomerulonephritis in the future.

Animals↗
PubMed1995

[Airway continuous positive pressure in acute respiratory failure caused by Pneumocystis carinii pneumonia].

OBJECTIVE: To evaluate the efficiency of continuous positive airway pressure through a face mask in acute respiratory insufficiency (ARI) secondary to Pneumocystis carinii pneumonia. DESIGN: Prospective study. SETTING: Multidisciplinary ICU. PATIENTS: Fifteen patients with ARI secondary to Pneumocystis carinii pneumonia were studied. INTERVENTIONS: Initially al patients received high flow oxygen therapy through a face mask for 60 minutes (Pre-CPAP phase); then CPAP through a face mask, with identical FiO2 and for a similar period of time (Pst-CPAP phase). At the end of each phase the following parameters were evaluated: respiratory rate, heart rate, arterial gases, acid-base balance, and respiratory muscle motility. MEASUREMENTS: After oxygen therapy all fifteen patients had similar variables. After 60 minutes with CPAP through a face mask, significant improvements were noted for respiratory rate, heart rate, muscular effort, PaO2, SaO2, and PaO2/FiO2 (p < 0.001) in eleven patients, who survived after a mean stay of 8.5 days in the ICU with no evidence of major complications. In contrast, CPAP failed in four patients as respiratory rate, heart rate and vigorous muscle effort remained unchanged and, although PaO2 and SaO2 increased, the obtained values were significantly lower than in the remaining patients. Consequently, they underwent intubation and mechanical ventilation and after a mean stay of fourteen days with this ventilatory option died. CONCLUSIONS: These results confirm that CPAP through a face mask is an effective means to improve oxygenation in patients with Pneumocystis carinii pneumonia who develop hypoxemic respiratory insufficiency. Its early introduction in hospital protocols can help improving the prognosis in certain patients with severe PCP and avoid their admission to ICU, which would be thus preserved for those patients requiring mechanical ventilation.

Acute Disease↗