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Biomedical subjects

M Ferrer

Publications and source records attributed to M Ferrer.

At least 109 records · Page 6Linked to original sources
PubMed1998

Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.

Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.

Adolescent↗
PubMed1998

Respiratory mechanics in ventilated COPD patients: forced oscillation versus occlusion techniques.

The respiratory mechanics of artificially ventilated chronic obstructive pulmonary disease (COPD) patients were investigated by means of the forced oscillation (FOT) and the end-inspiratory airway occlusion (AOT) techniques. FOT was applied to measure respiratory resistance (Rrs) and reactance (Xrs) from 0.25-16 Hz. Maximum (Rmax) and minimum (Rmin) resistances, static elastance (Est) and time constant (T) were computed by AOT. FOT and AOT data were interpreted with models featuring airway wall shunt, tissue viscoelasticity and parallel inhomogeneity. Rrs* and Xrs*, predicted from the AOT data, were computed and compared with Rrs and Xrs measured by FOT. Rrs and Xrs (hPa x s x L(-1)) decreased from 31.2+/-10.3 to 5.9+/-4.6 and increased from -20.3+/-7.1 to -8.0+/-4.4 from 0.25-16 Hz, respectively. Central resistance (Rc) and peripheral resistance (Rp) (in hPa x s x L(-1)), and shunt elastance (Esh) and tissue elastance (Et) (in hPa x L(-1)) were 4.4+/-5.4, 28.4+/-153, 723+/-393 and 31.8+/-10.1, respectively. Rmin, Rmax and Est were 18.4+/-5.9, 28.4+/-12.8 and 18.1+/-4.2 respectively, and T=0.76+/-0.25 s. The frequency dependence of predicted Rrs* and Xrs* differed markedly from that of measured Rrs and Xrs. The use of different models to interpret the measured data suggests that both airway and tissue properties determined the frequency dependence of respiratory resistance and respiratory reactance in ventilated chronic obstructive pulmonary disease patients at the investigated frequencies (0.25-16 Hz).

Airway Resistance↗
PubMed1998

Assessment of ventilation-perfusion mismatching in mechanically ventilated patients.

The multiple inert gas elimination technique (MIGET) is a robust tool to assess both ventilation-perfusion (V'A/Q') distributions and the role of extrapulmonary factors determining arterial oxygenation during spontaneous breathing and in mechanically ventilated patients. Mixed expired gas sampling used in the MIGET is most often obtained from a 10-L mixing box (10L-MB) placed in the expiratory side of the ventilator circuit. Consequently, a considerable increase in the compression volume (Vc) would be expected which, in turn, can give rise to potential errors in the estimation of the effective tidal volume delivered to the patient. The effects of the 10L-MB on the Vc were compared with those produced by a newly designed 1-L, mixing box (IL-MB). At a given peak pressure (Ppeak) within the ventilator circuit, the Vc generated by the 10L-MB was about six-times higher than that produced by the 1L-MB. At a Ppeak =50 cmH2O, the Vc were 377 mL (10L-MB) and 67 mL (1L-MB) (p<0.001). In six patients, the mixed expired partial pressures of the six inert gases simultaneously collected from the two mixing boxes fell on the identity line. V'A/Q' distributions recovered using each of the two mixing boxes were equivalent. With the IL-MB, the effects of different positive end-expiratory pressure levels (0, 6 and 12 cmH2O) on Vc and arterial carbon dioxide tension were negligible. In conclusion, the new 1-L mixing box provides efficient gas mixing and substantially decreases the compression volume. It is, therefore, recommended when studies requiring mixed expired gas are performed in ventilated patients.

Aged↗
PubMed1998

Estrogen replacement modulates resistance artery smooth muscle and endothelial alpha2-adrenoceptor reactivity.

The purpose of this study was to evaluate the effects of estrogen replacement on ovariectomized rats on the reactivity to alpha2-adrenoceptor activation, and to analyze the role of the endothelium in modulating this response. Third order branches of the superior mesenteric artery from ovariectomized untreated (OvX) and estrogen-replaced (E2) Sprague-Dawley rats were cannulated and pressurized to 50 mmHg. Under relaxed conditions (0.1 mM papaverine), there were no differences in lumen diameter. Intact vessels from E2 rats were unresponsive to clonidine (0.01-10 microM); incubation in indomethacin (1 microM), a cyclooxygenase inhibitor, produced intermediate constriction that was significantly augmented by L-NNA (0.3 mM), a NO synthase inhibitor, or by endothelial denudation. Conversely, intact vessels from OvX animals constricted to clonidine in a concentration-dependent manner. This effect was significantly diminished by endothelial removal or indomethacin, but was not affected by L-NNA. Yohimbine (1 microM), an beta2 receptor antagonist, significantly diminished arterial sensitivity to, and efficacy of clonidine. These results suggest that estrogen replacement enhanced vasoconstriction induced by smooth muscle alpha2 adrenoceptor activation, although this effect was obscured in intact vessels due to an overriding influence of endothelial dilator substances, primarily NO. In arteries from OvX animals, smooth muscle was less sensitive to alpha2 agonist stimulation, however, the release of a vasoconstrictor prostanoid from the endothelium was predominant, and induced significant vasoconstriction.

Adrenergic alpha-Antagonists↗
PubMed1998

[Comparative study of the analyzers L-9100 (Merck-Hitachi) and HA-8121 (Menarini) for the determination of glycosylated hemoglobin].

A comparison study about the determination of HbA1c by L-9100 (Merck Hitachi) and HA-8121 (Menarini) was made. HbA1c was measured by high pressure liquid chromatography (HPLC). The within-run imprecision was CV < 3% (for HA-8121) and CV < 4.9% (for L-9100). The between-run imprecision was CV < 1% (for L-9100) and CV < 2% (for HA-121). Analysis of means (Student test) showed that both instruments were statistically different for HbA1Ac measurements (p < 0.001). The results of regression analysis (Passsing-Bablock test) were as follows: y = 0.88x + 0.58 (y = L-9100, r = 0.982, p = 0.005). In conclusion, the results showed that there are statistical differences between both instruments. Regression and correlation was good, but the data also showed that there is a constant and proportional error. We must make a new reference range values.

Chromatography, High Pressure Liquid↗
PubMed1997

Construction and characterization of a radio-iodinatable mutant of recombinant human CD4.

Recombinant soluble human CD4 (rsCD4) has been used in iodinated form to study the interaction of CD4 with its ligands. However, the utility of [125I]-rsCD4 is limited because rsCD4 is inefficiently iodinated and the iodinated protein is poorly active. The iodination properties of rsCD4 most likely reflect the poor accessibility of the tyrosine residues, apparent from the available X-ray structures. We have generated an iodinatable mutant of rsCD4 by substituting Tyr for Phe(179) in the flexible, solvent-exposed C-terminal region of rsCD4(183), a truncated form of CD4 that consists of the first 183 residues of CD4 and includes the binding sites for HIV-1 gp120 and MHC class II molecules. When F179Y rsCD4(183) is iodinated under trace-labeling conditions, the efficiency of 125I incorporation and the percentage of iodinated molecules that are active are much enhanced compared with WT rsCD4. Moreover, trace-labeled [125I]-F179Y rsCD4(183) has the same affinity for HIV-1 rgp120 as unlabeled WT rsCD4. The improved activity of trace-labeled [125I]-F179Y rsCD4(183) appears to be due to effective competition by Y179 for reactive iodine species that, in WT rsCD4, react with traces of denatured protein and/or with residues critical for activity or conformational integrity. The incorporation of accessible tyrosine residues may improve the iodinatibility of a protein both by introducing a readily iodinatable residue and by protecting sensitive proteins from adverse reactions.

Animals↗
PubMed1997

Chronic obstructive pulmonary disease stage and health-related quality of life. The Quality of Life of Chronic Obstructive Pulmonary Disease Study Group.

BACKGROUND: The American Thoracic Society recently recommended that chronic obstructive pulmonary disease be staged on the basis of the percentage of predicted FEV1. OBJECTIVE: To examine 1) the relation between the american Thoracic Society system for staging chronic obstructive pulmonary disease and health-related quality of life and 2) the effect of self-reported comorbid conditions on health-related quality of life. DESIGN: Cross-sectional study. SETTING: Outpatient clinics of respiratory departments of four hospitals and one primary health care center in spain. PATIENTS: 321 consecutive male patients with chronic obstructive pulmonary disease. MEASUREMENTS: Functional respiratory impairment, FEV1, respiratory symptoms, and health-related quality of life. Respiratory symptoms and health-related quality of life were measured by using the Spanish version of the St. George's Respiratory Questionnaire and the Nottingham Health Profile. RESULTS: Patient scores on the St. George's Respiratory Questionnaire were moderately to strongly associated with disease staging (r = 0.27 to 0.51). Compared with reference values, values for health-related quality of life for patients with stage I disease were substantially higher on the St. George's Respiratory Questionnaire (6 and 34; p < 0.001) and values for impairment were significantly greater in stage 1 patients with comorbid conditions (19 and 36; P = 0.001). At least one concomitant chronic condition was found in 84% of study patients. Comorbid conditions only partly influenced the observed pattern of deterioration of health-related quality of life with worsening stages of disease. CONCLUSION: Staging criteria for chronic obstructive pulmonary disease based on percentage of predicted FEV1 separated groups of patients with varying degrees of impairment in health-related quality of life. Contrary to expectations, even patients with mild disease showed substantially compromised health-related quality of life. Comorbid conditions influenced the relation between chronic obstructive pulmonary disease and health-related quality of life.

Comorbidity↗
PubMed1997

Involvement of protein kinase C in the supersensitivity to 5-HT caused by oxidized low-density lipoproteins.

The effect of native (n-LDL) and oxidized (ox-LDL) low-density lipoproteins and lysophosphatidylcholines (LPCs) on: (1) vasodilator responses induced by acetylcholine (ACh) in intact rabbit aorta segments, and (2) vasoconstrictor responses to serotonin (5-HT), and potassium (K+) in endothelium denuded segments was investigated. In intact vessels, 100 microg/ml ox-LDL did not modify ACh-induced relaxation, while it was diminished by 300 microg/ml ox-LDL and abolished by 50 microM LPCs. In contrast, this relaxation was unaltered by n-LDL (100 or 300 microg/ml). In deendothelialized arteries, 100 and 300 microg/ml n-LDL as well as 50 microM LPCs did not modify the contractions induced by 5-HT or K+, while 100 or 300 microg/ml ox-LDL increased the 5-HT-induced contraction, without altering those induced by 75 mM K+. Incubation with 100 or 300 microg/ml ox-LDL increased the contractile response to the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDB) (0.1-1 microM) in a concentration-dependent manner, which was blocked by staurosporine (0.1 microM), and unaltered by (50 microM) calphostin C or (50 microM) chelerythrine, the three are PKC inhibitors. Preincubation with 0.05 microM PDB increased the contraction elicited by 5-HT, while staurosporine decreased the PDB-induced contraction, and prevented the 5-HT response increase caused by 300 microg/ml ox-LDL. These results suggest that only ox-LDL reduces endothelium-dependent relaxation and elicits PKC activation, and that this activation mediates, at least in part, the vasoconstrictor response to 5-HT.

Acetylcholine↗
PubMed1997

Differences in immunological response to a T. gondii protein (SAG1) derived peptide between two strains of mice: effect on protection in T. gondii infection.

This study presents the analysis of the immunogenicity, antigenicity and protective effects of a peptide derived from the major surface antigen of Toxoplasma gondii, SAG1. This synthetic peptide carrying three predicted H-2k restricted T cell epitopes was used to immunize mice. The protective effect of the peptide was evaluated in CBA/J and C57BL/6 mice using the decrease in brain cyst load as evidence of protection. Immunization of C57BL/6 mice yielded high antibody titres but had no protective effect after oral challenge. Immunized CBA/J, mice which responded with a lower titre, showed a 35% reduction in cyst burden after oral challenge. Both strains yielded antibodies which recognized the cognate SAG1 protein on immunoblot assay. Using the BIAcore, system, it was shown that at lower titres the CBA/J mouse sera recognized the native SAG1 protein more effectively than the C57BL/6 mouse sera, yielding much higher anti-peptide titres. Lymphoproliferation assays using the peptide experimentally confirmed the predicted T-cell epitopes and showed that they were also recognized by cells of T. gondii infected mice. The anti-peptide subclass analysis suggested a Th1 orientation in CBA/J mice, whereas a Th2 orientation was observed in C57BL/6 mice. Finally, fine analysis of sequences recognized under MHC class I indicated the existence of a T-cell epitope in the H-2k haplotype (CBA/J mice) but not in the H-2b haplotype (C57BL/6 mice). This study provides a structural basis to the understanding of the vaccination response to one of the T. gondii antigens in different strains of mice.

Animals↗
PubMed1997

Are results of the SF-36 health survey and the Nottingham Health Profile similar? A comparison in COPD patients. Quality of Life in COPD Study Group.

A number of questionnaires have been used to assess the health-related quality of life of patients with chronic obstructive pulmonary disease (COPD). The study compares the performance of the SF-36 and the Nottingham Health Profile (NHP) in a sample of 321 male patients with COPD. Score distributions, reliability estimates, and several item scaling tests, including Rasch analysis were compared. Finally, we assessed the relative ability of the two instruments considered in discriminating different levels of disease severity by comparing: (a) their correlations with dyspnea and %FEV1; the receiver operating characteristic (ROC) curves; and the F-statistics. The SF-36 scores were less skewed and more homogeneously distributed than NHP scores. Item scaling tests and reliability estimates showed a better performance of SF-36 items and scales. Nevertheless, results of Rasch analysis evidenced that both instruments have very similar scaling characteristics. Validity results did not show a consistent pattern of superiority for either of the instruments. For the physical domain, correlations of NHP and SF-36 scores with %FEV1 and dyspnea were very similar and substantial (tau > or = 0.30). F-statistics showed that SF-36 physical scale was more precise (86%) than the NHP counterpart in discriminating among levels of dyspnea and %FEV1 impairment. Nevertheless, the ROC curve and its associated area under the curve did not show a significant difference (p > 0.10). Overall results suggest that both instruments are similar in discriminating among different levels of respiratory impairment.

Data Interpretation, Statistical↗
PubMed1997

Molecular cloning and functional characterization of the human cytosolic malic enzyme promoter: thyroid hormone responsiveness.

We report the structural and functional features of the 5'-flanking region of the human cytosolic malic enzyme (ME) gene. A 2.2-kb subclone, comprising 1.5 kb upstream of the translation initiation codon, the first exon, and 0.7 kb of flanking intronic region, was sequenced and mapped to chromosome 6. The proximal promoter region is rich in G + C, lacks TATA or CCAAT boxes, and shows multiple transcription start sites, the major one 106 nucleotides upstream the ATG codon. Sequences -59/-13 and -137/-103 conferred maximal promoter activity. Deletional analysis revealed the presence of two regions positively regulated by 3,5,3'-triiodo-L-thyronine (T3). The proximal region confers the strongest T3 inducibility to the human ME as well as to a heterologous promoter. Thyroid hormone receptor beta (TRbeta) binds to an inverted palindromic T3 response element (TRE) at position -105/-87 in a manner that is prevented by T3. Nuclear extracts or in vitro-translated retinoid acid receptor alpha (RXR alpha) shifted the TRbeta retarded band to slower-mobility complexes, which are unaffected by T3. In the absence of T3, overexpression of TRbeta repressed the ME promoter activity, most probably, through binding of TRbeta homodimers to the TRE. Thus, T3 seems to control ME transcription by inducing the dissociation of TRbeta homodimers and the functional activation of liganded heterodimers.

Base Sequence↗
PubMed1997

Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease.

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 +/- 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (I) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 +/- 2 cm H20, PEEP = 3 +/- 2 cm H20); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping FIO2 constant (0.23 +/- 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in Pa02 (from 50 +/- 6 to 57 +/- 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 +/- 10 to 59 +/- 10 mm Hg; p < 0.0001), but AaPO2 increased (from 39 +/- 13 to 48 +/- 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 +/- 5 to 19 +/- 3 breaths/min; p < 0.0001), tidal volume increased (from 311 +/- 42 to 520 +/- 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 +/- 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 +/- 1.6 to 5.8 +/- 1.3 L/min; p < 0.0025) with no impact on mixed venous PO2. No substantial changes in VA/Q mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 +/- 0.17 to 0.90 +/- 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in VA/Q relationships. The increase in AaPO2 was explained by the rise in R due to an increased clearance of body stores of C02 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NlPPV in this type of patient.

Acute Disease↗
PubMed1997

Effect of acetylsalicylic acid on pulmonary gas exchange in patients with severe pneumonia: a pilot study.

BACKGROUND: It has been hypothesized that local release of prostacyclin in acute pneumonia may ablate hypoxic pulmonary vasoconstriction, thus contributing to the impairment of pulmonary gas exchange in these patients. Inhibition of cyclooxygenase pathway could prevent this phenomenon by reducing the release of these metabolites. METHODS: A study was designed to assess the effect of I.V. acetylsalicylic acid (ASA) (2 g) on pulmonary gas exchange in seven patients (age, 64+/-11 [mean+/-SD] years) with unilateral severe pneumonia (PaO2/fraction of inspired oxygen, 168+/-67) needing mechanical ventilation. Respiratory gases, pulmonary and systemic hemodynamics, and ventilation-perfusion (VA/Q) distributions were studied before and 15 and 60 min after the infusion of ASA. RESULTS: At baseline, the amount of shunt (VA/Q ratios <0.005) was 28+/-17% of cardiac output, blood flow to areas with low VA/Q ratios (<0.1, excluding shunt) was 8+/-7%, and the dispersion of pulmonary blood flow distribution (second moment, log SD Q) was 1.45+/-0.49 (normal range, 0.3 to 0.6). Sixty minutes after the infusion of ASA, we observed a mild reduction of the amount of shunt, from 28+/-17% to 23.5+/-13% (p<0.05) without changes in arterial oxygenation. This was associated with a significant increase in mean pulmonary artery pressure (from 21.9+/-3.6 to 24.4+/-5.1 and 23.9+/-5.3 mm Hg, p<0.025 and p=0.1) and pulmonary vascular resistance (from 1.4+/-0.9 to 1.8+/-0.8 and 1.8+/-1.3 mm Hg x min x L(-1) , p<0.002 and p=0.11) 15 and 60 min after ASA, respectively. The ASA plasma levels were within the normal therapeutic range (120+/-7 microg/mL, 15 min, and 113+/-11 microg/mL, 60 min after ASA infusion). CONCLUSIONS: Although there was a modest improvement in intrapulmonary shunt, our results suggest that perfusion of ASA in this small sample of patients with severe pneumonia appears to be of little benefit as complementary treatment for severe hypoxemia.

Adult↗
PubMed1997

Unmet health care needs and mortality among Spanish elderly.

OBJECTIVES: This study estimates the prevalence of unmet health care needs among the elderly of Barcelona, Spain, and analyzes the association between unmet needs and mortality. METHODS: Home interviews were conducted with 1315 elderly in Barcelona. Individuals were classified as having a "health services need" if they reported being in fair, poor, or very poor health; suffering from two or more chronic conditions; or being dependent in at least one basic activity of daily living. Need was considered unmet if no visits to or from a physician in the previous 12 months were reported. Mortality was assessed from census data in August 1991. RESULTS: Between 10% and 25% of the elderly in need reported no use of health services. After a median of 60.3 months, those with unmet health care needs presented a higher risk of mortality, adjusted for several confounding factors: relative risk [RR] = 2.55 (95% confidence interval [CI] = 1.22, 5.32) for unmet activity of daily living dependency; RR = 1.80 (95% CI = 1.20, 2.70) for unmet comorbidity; and odds ratio = 1.10 (95% CI = 0.59, 2.05) for unmet poor self-rated health. CONCLUSION: Noninstitutionalized elderly individuals with unmet health care needs are at increased risk of dying.

Activities of Daily Living↗
PubMed1996

COOH-terminal extended recombinant amphiregulin with bioactivity comparable with naturally derived growth factor.

The mature secreted form of the epidermal growth factor (EGF) receptor ligand amphiregulin (AR) is reported to be an 84-amino acid residue polypeptide, which is generated by proteolytic processing of a 252-amino acid precursor. This form of recombinant AR (rAR84) and two forms with COOH-terminal extensions corresponding to sequences from the AR precursor (rAR87 and rAR92) were expressed at high levels in Escherichia coli, oxidized to the correct disulfide arrangement, and purified to homogeneity. rAR84 competed poorly for binding of radiolabeled EGF to the EGF receptor and had little ability to stimulate growth of Balb/c/3T3 cells. In striking contrast, rAR87 and rAR92 possessed 42- and 20-fold greater receptor binding activity and 55- and 14-fold greater bioactivity, respectively. Furthermore, addition of the COOH-terminal four amino acids from transforming growth factor alpha to the COOH terminus of rAR84 improved the activity of rAR84 by 100- and 1000-fold, respectively, in these assays. rAR87 was found to have approximately 32% of the specific activity of natural AR from MCF-7 cells when compared in two different bioassays. These findings strongly suggest that the 84-amino acid sequence is not the correct structure of the naturally occurring secreted form of AR and that natural AR contains additional amino acid residues at the COOH-terminal end.

3T3 Cells↗
PubMed1996

Effect of clenbuterol on the modulation of noradrenaline release in the rat tail artery.

1. Exposure of rat tail arteries to clenbuterol, a beta 2-adrenoceptor agonist, for 20 or 90 min, did not change or increase, respectively, tritium overflow induced by electrical field stimulation in arteries preincubated with [3H]-noradrenaline (NA). This facilitatory effect was antagonized by propranolol. 2. Phentolamine increased the evoked overflow four-fold, which was not modified by 90 min incubation with clenbuterol. In rats pretreated with clenbuterol for 2 weeks, the stimulated overflow was not enhanced by this beta 2-agonist, and the increase produced by phentolamine was markedly diminished. 3. Contractile responses induced by electrical field stimulation were not modified or increased (only at low frequencies) by preincubation with clenbuterol for 20 or 90 min, respectively. This effect was inhibited by propranolol. 4. In arteries precontracted with 5-hydroxytryptamine, clenbuterol (10 nM-10 microM) produced small relaxations, which were reduced by propranolol plus phentolamine and not modified by phentolamine or 90 min exposure to clenbuterol. 5. These results indicate that prolonged exposure of rat tail arteries to clenbuterol produces a facilitation of NA release mediated by activation of presynaptic beta 2-adrenoceptors, which may be involved on the enhancement of contractile responses to electrical stimulation induced by clenbuterol. However, chronic treatment with this beta-agonist desensitizes these receptors.

Adrenergic beta-Agonists↗
PubMed1996

Changes in intestinal alpha-methyl-D-glucoside uptake due to pregnancy and lactation in rats.

Uptake of alpha-methyl-D-glucoside, a nonmetabolizable glucose analogue, by everted intestinal sleeves was studied in virgin, pregnant and lactating rats. The animals showed an increase in jejunal and ileal tissue mass, mucosal mass, nominal surface area, and enzymatic activities. No changes were observed in the carrier affinity throughout the breeding stages. Nevertheless there was a significant increase in glucose carrier density (Vmax) per unit of length of jejunum and ileum in pregnant and lactating animals. Integrating the results obtained, and increased overall ability to transport hexoses by nonspecific adaptation can be observed in breeding stages.

Animals↗