Biomedical subjects

J Roca

Publications and source records attributed to J Roca.

At least 55 records · Page 3Linked to original sources

PubMed2002

Association of systemic lupus erythematosus and hypermobility.

OBJECTIVE: To investigate joint laxity in patients with systemic lupus erythematosus (SLE). SETTING: University Hospital. METHODS: 81 patients with SLE (1999 American College of Rheumatology criteria; 72 (89%) women and nine (11%) men, mean age 42.9 (SD 16.1) years), who regularly attended a specialist SLE clinic were examined. The control group comprised 280 patients attending a general practitioner (193 (69%) women and 87 (31%) men, mean age 44.7 (SD 11.2) years). Joint laxity was measured according to the criteria of Beighton et al (total score 4 or more). A regression analysis was performed. RESULTS: Thirty nine (48%) patients with SLE and 42 (15%) of the control group were hypermobile. A logistic regression model was developed. The odds ratio of the association between laxity and SLE after adjustment for age and sex was 2.31 in the group younger than 49 years, and 17.99 in the group aged 49 years or older. Neither the clinical and analytical profile nor the use of corticosteroids was related to joint laxity. CONCLUSION: Patients with SLE showed more hypermobility than controls. Hypermobility was more profound in older patients with SLE (> or =49 years). Joint laxity was not associated with any clinical or analytical pattern. Treatment with corticosteroids was not related to joint laxity.

Adult↗

PubMed2002

Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD.

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.

Aged↗

PubMed2002

Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma.

Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage. This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge. Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93+/-4 mmHg; P: 83+/-4 mmHg) at 45 min, without influencing the increases in Rrs. In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.

Administration, Inhalation↗

PubMed2002

Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an in vitro study.

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulus in vitro in COPD, and the role of endothelium-derived nitric oxide (NO) in this response. The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+ hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO. Compared with the other groups, HV was reduced in COPDH. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV. In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.

Aged↗

PubMed2002

A portable forced oscillation device for respiratory home monitoring.

The increase in the prevalence of chronic respiratory diseases has resulted in a rise in health services provided at home. The forced oscillation technique (FOT) proves to be a useful tool when it is desired to assess lung function noninvasively, and particularly for patients in whom spirometry cannot be applied. As no portable FOT device is currently available, the aim of this study was to design and test a portable FOT system for ambulatory and home care applications. The system devised is based on a microprocessor, which allows online computation of respiratory resistance (Rrs) and reactance (Xrs) and reliability indices. The portable device was compared with a conventional FOT system by using signals from 14 patients with chronic respiratory disease. This device has the same computation capabilities and flexibility as conventional FOT systems and meets the requirements for home application. Rrs (14.2 +/- 6.0 cmH2O x s x L(-1), mean +/- SD) and Xrs (-5.3 +/- 2.7 cmH2O x s x L(-1)) measured at 5 Hz by the portable system virtually coincided with those computed with the reference conventional FOT system: mean differences +/-SD were 0.074 +/- 0.025 and 0.005 +/- 0.009 cmH2O x s x L(-1), respectively. This portable forced oscillation technique device could be a useful tool for monitoring respiratory mechanics in ambulatory and home care applications.

Airway Resistance↗

PubMed2002

Physiological responses to the 6-min walk test in patients with chronic obstructive pulmonary disease.

The 6-min walking test (6MWT) is frequently used to assess functional capacity in chronic cardiopulmonary disorders because of its simplicity. The study examines the physiological responses during encouraged 6MWT in patients with chronic obstructive pulmonary disease. Pulmonary oxygen (O2) uptake (V'O2) was measured in 20 male patients (age 66+/-6 yrs, forced expiratory volume in one second 45+/-14% predicted) during 6MWT and incremental cycling, in random order. O2 tension in arterial blood, carbon dioxide tension in arterial blood and arterial lactate concentration ([La]art) were obtained in the last 10 patients. During the 6MWT, V'O2 showed a plateau after the 3rd min (1.39+/-0.28, 1.42+/-0.31, and 1.40+/-0.30 L x min(-1), 4th, 5th and 6th min, respectively), and minute ventilation (V'E) (42+/-8 L x min(-1)) was 91% maximal voluntary ventilation. No differences were shown between 6MWT (6th min) and peak cycling exercise in V'O2 (1.40+/-0.30 versus 1.41+/-0.28 L x min(-1), respectively), cardiac frequency (126+/-13 versus 130+/-12 beats x min(-1)), or arterial respiratory blood gases. The two tests were significantly different in V'E (42+/-8 versus 47+/-8 L x min(-1), 6MWT versus cycling, respectively), carbon dioxide production (1.30+/-0.31 versus 1.45+/-0.18 L x min(-1)) and [La]art (2.9+/-1.99 versus 5.9+/-1.51 M). The study demonstrates that an encouraged 6-min walking test generates a high but sustainable oxygen uptake. Since the oxygen uptake plateau reflects the integrated response of the system, it may explain the high prognostic value of the 6-min walking test.

Aged↗

PubMed2002

Minimum number of spermatozoa required for normal fertility after deep intrauterine insemination in non-sedated sows.

A fibreoptic endoscope procedure for non-surgical deep intrauterine insemination in non-sedated sows has been reported. However, the endoscope is an expensive and fragile instrument, and is unsuitable for use under field conditions. The aim of this study was to determine the minimum number of spermatozoa required to maintain optimal fertility using a flexible catheter (1.8 m in length, 4 mm in diameter) for deep intrauterine insemination in 2-6 parity non-sedated sows. Crossbred sows were treated with eCG 24 h after weaning and with hCG 72 h later to induce oestrus. Deep intrauterine insemination was performed 36 h after hCG treatment in 117, 126, 60 and 69 sows with 15.0, 5.0, 2.5 or 1.0 x 10(7) spermatozoa in 10 ml, respectively. Weaned sows (n = 147) not treated with hormones and used for standard artificial insemination (AI) (two inseminations per oestrus with 3 x 10(9) spermatozoa in 100 ml) served as controls. The flexible catheter was passed successfully through the cervix into one uterine horn in 95.4% of the sows in an average of 3.7 +/- 0.09 min. Farrowing rates after deep intrauterine insemination with 15 or 5 x 10(7) spermatozoa did not differ from those of the control group (82.9, 76.2 and 83.0%, respectively), but a significant decrease (P < 0.001) was observed in sows inseminated with 2.5 or 1.0 x 10(7) spermatozoa (46.7 and 39.1%, respectively). In contrast, the number of spermatozoa inseminated did not affect prolificacy. Laparotomy revealed that the tip of the flexible catheter reached approximately the anterior third of the uterine horn. Although deep intrauterine insemination was performed in only one uterine horn, the percentages of embryos collected from the tip of both uterine horns 2 days after deep insemination were not significantly different. The results show that in comparison with standard AI, a 20-60-fold reduction in the number of spermatozoa inseminated and an 8-10-fold reduction in the dose volume can be achieved without decreasing fertility when semen is deposited non-surgically into the upper first third of one uterine horn.

Animals↗

PubMed2001

Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome.

To investigate the mechanisms underlying improvement of arterial oxygenation during a protective ventilatory strategy (PVS) in early acute respiratory distress syndrome (ARDS), we studied eight patients during volume-controlled mechanical ventilation, keeping respiratory rate and fraction of inspired oxygen (FI(O(2))) (0.82 +/- 0.20) unchanged: (1) at baseline (tidal volume [VT] 10 to 12 ml x kg(-1); positive end-expiratory pressure [PEEP] 8 to 10 cm H(2)O); (2) during PVS (PEEP 2 cm H(2)O above the low inflexion point (P(FLEX)) and VT of 5 to 7 ml x kg(-1)); and (3) post-PVS, back to baseline conditions. Inert gas measurements were done after 30 min in each ventilatory modality. During PVS, Pa(O(2)) increased significantly from 93 +/- 27 to 166 +/- 77 mm Hg (p < 0.008) and Pa(CO(2)) rose from 39 +/- 7 to 57 +/- 11 mm Hg (p < 0.0002) because of the decrease in minute ventilation (V E) (-3.6 L x min(-1)) (p < 0.005). Both heart rate (HR, +13 min(-1)) (p < 0.002) and cardiac output (Q, +1.2 L x min(-1)) (p < 0.05) increased. Static respiratory system linear compliance increased from 36 +/- 14 to 44 +/- 16 ml. cm H(2)O(-1) (p < 0.0002). PVS provoked recruitment of previously collapsed alveoli and redistribution of pulmonary blood flow from nonventilated alveoli to normal lung. Despite the increase in Q, intrapulmonary shunt fell from 39 +/- 15% to 31 +/- 11% (p < 0.04). We conclude that the decrease in intrapulmonary shunt owing to alveolar recruitment remains the pivotal mechanism to explain improvement of arterial oxygenation during this PVS.

Adult↗

PubMed2001

Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease.

The present study was undertaken to test whether endurance training in patients with COPD, along with enhancement of muscle bioenergetics, decreases muscle redox capacity as a result of recurrent episodes of cell hypoxia induced by high intensity exercise sessions. Seventeen patients with COPD (FEV(1), 38 +/- 4% pred; PaO2), 69 +/- 2.7 mm Hg; PaCO2, 42 +/- 1.7 mm Hg) and five age-matched control subjects (C) were studied pretraining and post-training. Reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and gamma-glutamyl cysteine synthase heavy subunit chain mRNA expression (gammaGCS-HS mRNA) were measured in the vastus lateralis. Pretraining redox status at rest and after moderate (40% Wpeak) constant-work rate exercise were similar between groups. After training (DeltaWpeak, 27 +/- 7% and 37 +/- 18%, COPD and C, respectively) (p < 0.05 each), GSSG levels increased only in patients with COPD (from 0.7 +/- 0.08 to 1.0 +/- 0.15 nmol/ mg protein, p < 0.05) with maintenance of GSH levels, whereas GSH markedly increased in C (from 4.6 +/- 1.03 to 8.7 +/- 0.41 nmol/ mg protein, p < 0.01). Post-training gammaGCS-HS mRNA levels increased after submaximal exercise in patients with COPD. No evidence of lipid peroxidation was observed. We conclude that although endurance training increased muscle redox potential in healthy subjects, patients with COPD showed a reduced ability to adapt to endurance training reflected in lower capacity to synthesize GSH.

Aged↗

PubMed2001

Oscillatory resistance measured during noninvasive proportional assist ventilation.

Setting proportional assist ventilation (PAV) requires the measurement of patient resistance and elastance. To avoid patient sedation/paralysis or the use of an esophageal balloon, noninvasive PAV is indirectly set by the "runaway" method or in accordance with patient comfort. The aim of this study was to ascertain whether the forced oscillation technique (FOT) applied by the ventilator during noninvasive PAV is useful in assessing patient respiratory resistance. Nasal PAV was applied to 14 patients with severe chronic obstructive pulmonary disease. During PAV a modified ventilator applied a 5-Hz pressure oscillation to noninvasively assess FOT resistance (Rrs). Lung resistance (RL) was measured in seven of the patients by using an esophageal balloon. Moreover, measurements were also performed in five of the patients when PAV was applied through the mouth. Rrs was close to RL both during nasal (Rrs = 8.9 +/- 3.1, RL = 9.0 +/- 2.6; cm H(2)O x s/L; n = 7, p > 0.05) and mouth (Rrs = 5.6 +/- 2.1, RL = 5.8 +/- 1.4; cm H(2)O x s/L; n = 5, p > 0.05) breathing. Rrs was slightly greater than the maximum value of flow assistance applied during the setting of PAV (FAmax): 11.1 +/- 5.4 and 9.5 +/- 2.9 cm H(2)O x s/L, respectively (n = 14, p > 0.05), both variables being significantly correlated (r = 0.72, p < 0.05). FOT applied by the PAV ventilator allowed the assessment of patient resistance. These results suggest that FOT could be useful in setting PAV flow assistance and in automatically and continuously updating this setting in accordance with patient resistance.

Aged↗

PubMed2001

Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers.

Cigarette smoking has been associated with alterations in the structure and endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1 are endothelium-derived mediators with opposite effects on vascular tone and cell growth. To investigate whether cigarette smoking could induce changes in the synthesis of these mediators in pulmonary arteries, we compared the expression of both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was evaluated by immunohistochemistry. In protein extracts of lung tissue, the content of eNOS protein was assessed by Western blot analysis and that of endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in arterial endothelium and the eNOS protein content in lung tissue were lower in the smokers than in the nonsmokers. No differences were shown in cell expression and protein content of endothelin-1 between both groups. We conclude that cigarette smoking is associated with reduced expression of eNOS in pulmonary arteries. The diminished synthesis of nitric oxide may contribute to the alterations in the structure and endothelial function of pulmonary vessels in cigarette-smoke-induced respiratory disease.

Aged↗

PubMed2001

Pulmonary gas exchange and sputum cellular responses to inhaled leukotriene D(4) in asthma.

Inhalational challenges with inflammatory mediators may provoke lung function disturbances similar to those shown in spontaneous acute asthma. Cysteinyl leukotrienes (CysLTs) have recently been established as mediators of bronchoconstriction in asthma but their effects on pulmonary gas exchange in asthma have not been assessed. We therefore investigated the effects of leukotriene D(4) (LTD(4)) challenge resulting in a significant decrease in FEV(1) (mean +/- SE, by 32 +/- 3%) in 13 nonsmoking, mild asthmatics. Respiratory system resistance (Rrs), and respiratory and inert gases were measured before and immediately after, and at 15 and 45 min after challenge. After bronchoprovocation, Rrs increased (by 106 +/- 12%), Pa(O(2)) decreased (by 25 +/- 4 mm Hg), and ventilation-perfusion distributions moderately to severely deteriorated, as shown by increases in the dispersions of pulmonary blood flow (Log SDQ, by 59 +/- 12%) and alveolar ventilation (Log SDV, by 65 +/- 20%) (p < 0.05 each). Sputum eosinophils (p < 0.05) and urinary LTE(4) (p < 0.005) increased after challenge. Despite the lack of mathematical correlations between spirometric and Rrs changes and gas exchange indices, the pattern of improvement of the functional variables after challenge ran in parallel. These findings support the evidence that CysLTs, in addition to being potent bronchoconstrictors, also provoke profound disturbances of pulmonary gas exchange in asthma.

Administration, Inhalation↗

PubMed2001

Novel display of knotted DNA molecules by two-dimensional gel electrophoresis.

We describe a two-dimensional agarose gel electrophoresis procedure that improves the resolution of knotted DNA molecules. The first gel dimension is run at low voltage, and DNA knots migrate according to their compactness. The second gel dimension is run at high voltage, and DNA knots migrate according to other physical parameters such as shape and flexibility. In comparison with one-dimensional gel electrophoresis, this procedure segregates the knotted DNA molecules from other unknotted forms of DNA, and partially resolves populations of knots that have the same number of crossings. The two-dimensional display may allow quantitative and qualitative characterization of different types of DNA knots simply by gel velocity.

Coliphages↗

PubMed2001

Effects of holding time during cooling and of type of package on plasma membrane integrity, motility and in vitro oocyte penetration ability of frozen-thawed boar spermatozoa.

The effect of a prolonged holding time (HT) during cooling on plasma membrane integrity (PMI), motility and in vitro oocyte penetration ability of boar spermatozoa frozen-thawed in different types of package was investigated. Boar semen was frozen in a split-sample design using 3 different HTs (3, 10 and 20 h) during cooling and three different types of freezing package: Maxi-straws, Medium-straws and FlatPacks. Assessment of PMI (SYBR-14 and propidium iodide, fluorescence microscopy) and sperm motility (visually and with CASA) was done during cooling (at 32 degrees C, 15 degrees C, 5 degrees C) and post-thaw (PT). The in vitro oocyte penetration ability of the spermatozoa was tested only PT, using a homologous in vitro penetration assay (hIVP). During cooling the HTs used had no significant (p<0.05) effect on either PMI or percentage of motile spermatozoa Post-thaw PMI was significantly higher (p<0.05) for 10 h and 20 h HT compared with 3 h, and the percentage of motile spermatozoa decreased significantly with 20 h HT as opposed to 3 h and 10 h. Regarding the freezing packages, the FlatPacks and Maxi-straws yielded significantly more PMI than did the Medium-straws (p<0.05). Post-thaw motility was significantly higher for FlatPacks than for straws, in terms of both percentage motile spermatozoa, and sperm velocity and lateral head displacement (LHD). The hIVP did not show any significant differences among the HTs, although FlatPacks yielded a significantly higher penetration rate and more spermatozoa per penetrated oocyte (p<0.05) than did the straws. Changes in motility patterns, toward a more circular motility during cooling and PT, could be noticed where individual spermatozoa showed a capacitation-like motility pattern. The changes were more obvious with 10-h and 20-h HTs than with 3-h HT.

Animals↗

PubMed2001

New 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives, with dual action at 5-HT1A serotonin receptors and serotonin transporter, as a new class of antidepressants.

In a search toward new and efficient antidepressants, 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives were designed, synthesized, and evaluated for 5-HT reuptake inhibition and 5-HT1A receptor antagonism. This dual pharmacological profile should lead, in principle, to a rapid and pronounced enhancement in serotoninergic neurotransmission and consequently to a more efficacious treatment of depression. The design was based on coupling structural moieties related to inhibition of serotonin reuptake, such as gamma-phenoxypropylamines, to arylpiperazines, typical 5-HT1A ligands. In binding studies, several compounds showed affinity at the 5-HT transporter and 5-HT1A receptors. Antidepressant-like activity was initially assayed in the forced swimming test with those compounds with Ki < 200 nM in both binding studies. Functional characterization was performed by measuring the intrinsic effect on rectal temperature in mice and also the antagonism to 8-OH-DPAT-induced hypothermia. The most efficacious compounds (12f, 23gE, 28a, and 28b) were further explored for their ability to antagonize 8-OH-DPAT-induced inhibition of forskolin-stimulated cAMP formation in a cell line expressing the 5-HT1A receptor. Furthermore, the antidepressant-like properties of 12f, 28a, and 28b, which exhibited 5-HT1A receptor antagonistic property in the latter study, were also evaluated in the learned helplessness test in rats. Among these three compounds, 28b (1-benzo[b]thiophene-3-yl)-3-[4-(2-methoxyphenyl)-1-ylpropan-1-ol) showed the higher affinity at both the 5-HT transporter and 5-HT1A receptors (Ki = 20 nM in both cases) and was also active in the other pharmacological tests. Such a pharmacological profile could lead to a new class of antidepressants with a dual mechanism of action and a faster onset of action.

Animals↗

PubMed2001

Varying levels of positive and negative supercoiling differently affect the efficiency with which topoisomerase II catenates and decatenates DNA.

Type II DNA topoisomerases catalyze the transport of one DNA double helix through another. Here, by using a non-hydrolyzable analog of ATP, I examined the single-step DNA transport preferences of the yeast type II topoisomerase bound to positively and negatively supercoiled DNA rings. I found that negative supercoiling favors decatenation of DNA rings more than positive supercoiling. Conversely, positive supercoiling favors the catenation and knotting of DNA rings more than negative supercoiling. This vectorial effect of DNA supercoiling handedness supports a model in which type II topoisomerases can recognize three DNA segments, and highlights a novel influence of DNA supercoiling in global DNA topology.

Blotting, Southern↗

PubMed2001

Hepatopulmonary syndrome in candidates for liver transplantation.

BACKGROUND: Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the clinical and pulmonary functional characteristics of HPS in candidates for orthotopic liver transplantation (OLT) and tested their predicted accuracy. METHODS: We studied 80 patients with cirrhosis prospectively, and carried out contrast-enhanced (CE) echocardiography and lung function tests, including ventilation-perfusion (V(A)/Q) distributions. RESULTS: Fourteen patients had HPS (incidence, 17.5%). Patients with HPS (49 +/- 12 (+/-SD) years) had more cutaneous spiders, finger clubbing and dyspnea (P < 0.05 each) and a lower diffusing capacity (DLCO, 56 +/- 18% predicted; P < 0.001) than non-HPS patients (n = 66). Mild to moderate V(A)/Q inequalities and increased intrapulmonary shunt were predominant in HPS patients, but oxygen diffusion impairment was observed in those with hypoxemia (n = 8) only. The DLCO showed a considerable area under the receiver operating characteristic curve (0.89). CONCLUSIONS: HPS in cirrhotic patient candidates for OLT shows a high incidence and these patients present with distinctive clinical and functional features compared with non-HPS individuals. The presence of a low DLCO may be of help for the diagnosis of HPS.

Adult↗

PubMed2001

New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin transporters, respectively. In GTPgammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action.

Animals↗