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Biomedical subjects

A López Farré

Publications and source records attributed to A López Farré.

11 recordsLinked to original sources
PubMed2005

[Erectile dysfunction: the role of laboratory in the diagnostic and pronostic evaluation].

OBJECTIVE: To review and to update the different laboratory tests recommended for etiologic diagnostic of erectile dysfunction and to evaluate the effect these tests could have on the pronostic and therapeutic strategy of this pathology. MATERIAL AND METHODS: We review the last articles related with etiopathogenics and pathophysiologics mechanisms of erectile dysfunction, including our studies on endothelial dysfunction and erectile dysfunction. RESULTS: The depth and extension of the laboratory protocol in erectile dysfunction is not necessaryly the same in all situations. The age, coincidence of comorbilities, set a different limit between patients demanding complementaries investigations that go beyond the basic request. CONCLUSIONS: The etiopathogenic laboratory work up in erectile dysfunction is currently changing incorporating news tests. The traditional search of commorbilities like diabetes, hepatic dysfunction, hypogonadism, hyperglucemia is getting broad with recents analitics evaluations related with potential markers of endothelial disease.

Clinical Laboratory Techniques↗
PubMed2003

BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay.

INTRODUCTION: The role of infiltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterising these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a lipido sterolic extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH. MATERIAL AND METHODS: A multicenter open pilot study of two parallel groups on BPH patients was carried out. They were randomized to receive either oral Permixon (P) 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (control group C). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Baseline clinical profile was almost identical in both groups in terms of age (65.7+/-5.1 vs. 67.1+/-5.8 years), IPSS (19.8+/-6.1 vs. 19.0+/-5.8), prostate volume (64.8+/-18.9 vs. 71.5+/-29.3cc), Q(max) (9.6+/-3.2 vs. 10.6+/-2.6 ml/s), and Q(L) (4.0+/-1.1 vs. 3.5+/-0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE and later prepared for immunohistochemical studies using CD3, CD20 and CD68 antibodies. Counting of positives cells, lymphoid aggregates and foci were done using EnVision technique and the Tech Mate processor. Cytokines, growth factors and eicosanoids were determined by Elisa kits following the manufactured recommendation. RESULTS: HISTOLOGICAL: A difference was observed in the number of lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show significant changes. CLINICAL: IPSS in the Permixon treated group was significantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment. COMMENTS: The BPH inflammatory hypothesis was tested in humans. Our pilot study shows a significant reduction of some inflammatory parameters in prostatic tissues of patients treated with Permixon. These biological findings justify a pharmacological effect of this drug on the inflammatory status of the adenoma. A correlation with clinical improvement was observed.

Adenoma↗
PubMed2001

Heart failure, redox alterations, and endothelial dysfunction.

Heart failure is characterized by neurohumoral alterations, such as activation of the sympathetic nervous system, stimulation of the renin-angiotensin system, increased activity of the endothelin system, increased production of norepinephrine, and increased circulating levels of cytokines. Oxidative stress is associated with the formation of reactive oxygen species (ROS). The myocardium has enzymes that stimulate ROS generation and enzymes with antioxidant effects. Several studies have suggested that ROS are increased in the failing heart. ROS may contribute to the pathophysiology of heart failure by initiating myocyte apoptosis and exerting direct negatively inotropic effects through the reduction of cytosolic intracellular free calcium. However, mechanisms such as endothelial dysfunction and inflammation have also been involved in the progression of heart failure. Antioxidants (eg, vitamin C) seem to improve endothelial functionality and reduce the inflammatory response in patients with heart failure. Therefore, in this review, we analyzed the involvement of ROS in the cellular and molecular mechanisms associated with endothelial dysfunction in heart failure.

Animals↗
PubMed2000

17 Beta-estradiol-stimulated nitric oxide production by neutrophils: effect on platelet activation.

OBJECTIVE: To evaluate the effect of 17beta-estradiol (E2) on the ability of human neutrophils to produce nitric oxide (NO) and its effects on platelet activation. METHODS: The expression of neuronal nitric oxide synthase (nNOS) protein and the formation of NO by 17beta-E2-incubated neutrophils from men were studied in vitro (ten male volunteers, no medical-surgical antecedents, aged 25-45 years). Platelet aggregometry and changes in cyclic guanosine monophospate (cGMP) levels were used to bioassay the functionality of NO released from neutrophils. RESULTS: Incubation of neutrophils derived from men with physiologic concentrations of 17beta-E2 (10(-10) to 10(-8) mol/L) enhanced the expression of nNOS protein. 17Beta-E2-incubated neutrophils also showed a significant increase in their ability to generate NO measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. Furthermore, 17beta-E2-incubated neutrophils showed a greater ability to prevent adenosine diphosphate (ADP)-induced platelet activation. Moreover, increased levels of cGMP were found in the coincubation of platelets with 17beta-E2-treated neutrophils. CONCLUSION: These results suggest that 17beta-E2 increases the ability of human neutrophils to produce NO and therefore may contribute to cardiovascular disease protection.

Adult↗
PubMed1998

Effects of angiotensin II on endothelial cell growth: role of AT-1 and AT-2 receptors.

Angiotensin II (AngII) is a main mediator in the regulation of vascular tone. Although its effects on vascular smooth muscle cells are well known, data on its role on endothelial biology are still insufficient. The present study examined the effect of endogenous and exogenous AngII on bovine aortic endothelial cells possessing both AT-1 and AT-2 receptors. A DNA synthesis-promoting effect of AT-2 blockade by PD123319 (10(-9) to 10(-7) M) was demonstrated. This effect was transduced through an AT-1-mediated pathway, as shown by using the AT-1 antagonist, losartan. In addition, an AT-1-mediated effect of AngII was demonstrated on bovine aortic endothelial cell proliferation, which occurred despite the absence of AngII-induced Ca2+ transients. In summary, the present study disclosed relevant characteristics of the effect of AngII on endothelial cell growth that have potential pathophysiologic projections, particularly for the use of selective AngII blocking agents.

Angiotensin II↗
PubMed1996

Role of endothelin in the pathophysiology of renal ischemia-reperfusion in normal rabbits.

The present study addressed the acute effects of endothelin-1 on renal function and neutrophils accumulation in the setting of in vivo severe (60 min) acute ischemia/reperfusion. Ischemia/reperfusion decreased renal functional parameters and increased renal neutrophil accumulation and medullary congestion. All these parameters markedly improved with the intrarenal administration of anti-endothelin-1 antiserum. Comparatively, the intrarenal infusion of endothelin-1 decreased renal function and increased neutrophil accumulation. Abnormalities in renal histology were, however, less pronounced than with ischemia/ reperfusion. In experiments using rabbit isolated perfused kidneys, endothelin-1 induced the accumulation of labeled neutrophils. This accumulation was similar to that observed in kidneys obtained after 60 minutes of ischemia plus 60 minutes of reperfusion. Both endothelin and ischemia/ reperfusion effects were counteracted by an anti-endothelin antibody. In further in vitro studies, we found that endothelin-1-induced the expression of the CD18 antigens on the neutrophil surface. In subsequent experiments based on this effect of ET-1 on CD18 antigens, a blockade of both ischemia/reperfusion-induced and endothelin-1-induced neutrophil accumulation was obtained by infusion an anti-CD18 antibody. In conclusion, our experiments disclosed the critical role of endothelin-1 as a major promoter of early neutrophil accumulation after ischemia/reperfusion, which occurred through an integrin-mediated mechanism.

Animals↗
PubMed1996

Endothelial cells inhibit NO generation by vascular smooth muscle cells. Role of transforming growth factor-beta.

Endothelial cell (EC)-released agents are active regulators of vascular smooth muscle cell (VSMC) functions. The first aim of the present work was to analyze the effect of ECs on interleukin-1 beta (IL-1 beta)-induced NO production by SMCs. Bovine aortic ECs (BAECs) and BVSMCs in culture were used for the study. IL-1 beta (0.03 U/L) stimulated nitrite production by BVSMCs. This increase was smaller in the presence of BAECs. This effect was accompanied by reduced expression of inducible NO synthase (iNOS) in BVSMCs coincubated with BAECs, as analyzed by Western blot analysis. The reduction in iNOS protein expression was partially reversed by a polyclonal antibody against transforming growth factor-beta (TGF-beta). Furthermore, we examined the cytotoxic effect of the NO released from BVSMCs on both BAECs and the BVSMCs themselves. Incubation of BAECs with IL-1 beta-prestimulated BVSMCs induced EC toxicity, which was partially inhibited by an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester, or an inhibitor of iNOS expression, dexamethasone. No cytotoxic effect of IL-1 beta on BVSMCs themselves was detected. ECs modulate iNOS expression in SMCs by mechanisms that include a TGF-beta-dependent pathway. The NO released from SMCs exerts cytotoxic effects on the adjacent endothelium without altering the viability of the SMCs.

Animals↗
PubMed1993

Nitric oxide-generating system as an autocrine mechanism in human polymorphonuclear leucocytes.

Recent data [Lopéz-Farré, Riesco, Moliz, Egido, Casado, Hernando and Caramelo (1991) Biochem. Biophys. Res. Commun. 178, 884-891] revealed that endothelin 1 (ET-1) increases intracellular free [Ca2+] in polymorphonuclear leucocytes (PMN) by a mechanism that can be inhibited by L-arginine. The aim of the present study was to clarify the mechanisms of the interaction between the effects of ET-1 and L-arginine in human PMN. The experimental findings showed that in human PMN: (a) ET-1 and the chemoattractant peptide N-formylmethionyl- leucyl-phenylalanine (fMLP) induce both the metabolism of L-arginine to L-citrulline and cyclic GMP (cGMP) formation; (b) the ET-1-induced cGMP production is inhibitable by the L-arginine antagonist NG-monomethyl-L-arginine, therefore suggesting the involvement of NO; (c) the ET-1- or fMLP-induced NO/cGMP stimulation is critically dependent on the availability of L-arginine; (d) human PMN possess a L-arginine transport system with both Na(+)-dependent and -independent components; (e) the L-arginine transport system in PMN appears to be feedback-regulated by NO/cGMP in ET-1-stimulated conditions, but not under baseline conditions; (f) the L-arginine transport system in PMN is independent of the gamma-glutamyl cycle and is not modified by either ET-1 or fMLP. The L-arginine/NO/cGMP-dependent mechanisms characterized in the present study may be relevant in the regulation of PMN activation in pathophysiological conditions in vivo.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart.

BACKGROUND: Based on recent evidence showing that endothelin-1 stimulates several activation mechanisms on neutrophils, the aim of the present study was to analyze the effects of endothelin-1 on neutrophil adhesion to endothelial cells and neutrophil accumulation in the heart. METHODS AND RESULTS: The experiments included (1) adhesion of 51Cr-labeled human neutrophils to bovine endothelial cells in culture both in the presence and absence of monoclonal antibodies against the alpha- and beta-subunits of integrins; (2) surface expression of the alpha- and beta-integrin antigens; (3) accumulation of 51Cr-labeled neutrophils on the isolated perfused rabbit heart; (4) in vivo accumulation of autologous neutrophils in the heart, as assessed by myeloperoxidase activity. Endothelin-1 stimulated neutrophil adhesion to endothelial cells (increase of 1 x 10(5) +/- 1 x 10(4) neutrophils per well). The endothelin-1-induced adhesion was blocked (83 +/- 6%) by the anti-CD18 antibody TS1/18 and by several anti-alpha-subunit antibodies. The expression of CD18 and CD11b on the neutrophil surface was also increased by endothelin-1. Endothelin-1 enhanced neutrophil accumulation in the isolated rabbit heart by 4.2 times throughout a TS1/18-inhibitable mechanism. Myeloperoxidase activity increased by 4.2 times in hearts infused in vivo with endothelin-1. CONCLUSIONS: Endothelin-1 stimulates neutrophil adhesion to endothelial cells by an effect on the expression of adhesive molecules on the neutrophil surface. Endothelin-1 stimulates neutrophil accumulation in vivo and in vitro in the heart. Antibodies against the integrin complex block the endothelin-1-dependent neutrophil adhesion. These findings have potential importance in the pathophysiology of endothelin-1-increased states.

Animals↗
PubMed1991

Mechanisms of renal effects of different agents stimulating production of cGMP.

The effect of agents stimulating the production of guanosine 3',5'-cyclic monophosphate (cGMP) by different mechanisms was compared in conscious unrestrained Wistar rats by administration of infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and atrial natriuretic peptide (ANP). ACh (10 micrograms.kg-1.min-1, n = 8), SNP (200 micrograms.kg-1.min-1, n = 8), and ANP (0.5 micrograms.kg-1.min-1, n = 7) induced natriuresis (urinary Na gradient: 399, 499, and 504 microeq/h, respectively; P less than 0.001 with respect to baseline) and diuresis (urine volume gradient: 0.87, 0.82, and 0.92 ml/h, respectively; P less than 0.001). Urinary cGMP increased (P less than 0.001) with the three agents (delta pmol cGMP/min: ACh 22.3, SNP 42.5, and ANP 48.4); in addition, a parallel increase in renal cGMP content was observed with the three agents (ACh 1.6, SNP 2.8, and ANP 3.5 times with respect to controls; P less than 0.05). Mean arterial pressure did not change with the aforementioned dose of ANP but decreased by 10 and 40% with ACh and SNP, respectively. Glomerular filtration rate increased by a similar magnitude with the three compounds. The competitive inhibitor of L-arginine, N omega-nitro-L-arginine (L-NNA), significantly decreased the diuretic, natriuretic, and hypotensive effects of ACh without affecting the actions of SNP and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗