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Biomedical subjects

A C Borges

Publications and source records attributed to A C Borges.

At least 37 records · Page 2Linked to original sources
PubMed2001

Combined dipyridamole and dobutamine echocardiography in myocardial hibernation: comparison with thallium uptake in patients after percutaneous transluminal coronary revascularization under circulatory support.

OBJECTIVE: To investigate the specificity and sensitivity of the combination of dipyridamole and dobutamine echocardiography for predicting functional recovery in patients with reduced ventricular function after coronary angioplasty. METHODS: Twenty-five patients, mean (SD) age 60.8 (10) years, with previous myocardial infarction (> 3 months), angiographically assessed coronary artery disease, and resting regional dysfunction (left ventricular ejection fraction < 35%) were studied. They underwent rest-redistribution thallium Tl-201 single photon emission computed tomography, and low-dose pharmacologic stress echocardiography with dobutamine (up to 10 microg/kg per minute), ultra low-dose dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine administration. RESULTS: The rate of agreement between Tl-201 and stress echo was 59% for dipyridamole, 62% for dobutamine, and 71% for combined dipyridamole-dobutamine (P <.05 vs dipyridamole and vs dobutamine). Combined dipyridamole-dobutamine showed a higher sensitivity (89%) than Tl-201, dobutamine, or dipyridamole (84%, 78%, and 80%). Specificity was lower for functional recovery prediction with Tl-201 (60%) compared with dobutamine (89%), dipyridamole (90%), and combined dipyridamole-dobutamine (91%). CONCLUSION: Thallium is more sensitive than dipyridamole or dobutamine; the sensitivity gap is filled with combined dipyridamole-dobutamine. Pharmacologic stress echocardiography is more specific than Tl-201 scintigraphy.

Adult↗
PubMed2001

Quantification of the effect of inhaled budesonide on airway inflammation in intermittent asthma by bronchitis index.

The bronchitis index (BI) is a scoring system for the visual quantification of airway inflammation by flexible bronchoscopy. A prospective study was carried out to determine whether patients with intermittent asthma present a considerable visible airway inflammation. Ten steroid-naive patients with intermittent asthma taking only inhaled beta2-agonists were enrolled and received budesonide (800 microg/day) over a period of 4 weeks. The airway inflammation was assessed by flexible electronic videobronchoscopy before and after the steroid treatment phase and quantified using the BI. Despite normal pulmonary function, all patients with intermittent asthma showed a marked visible airway inflammation that was reversed by a 4-week treatment with the inhaled steroid budesonide. The present study demonstrates that the BI may be useful as a clinical research tool for the assessment and quantification of airway inflammation in asthma. Furthermore, our results support the widely recognized theory that airway inflammation is present even in patients with mild asthma, and emphasize the necessity of an early therapy with inhaled steroids.

Administration, Inhalation↗
PubMed2001

The BMP antagonists cerberus-like and noggin do not interact during mouse forebrain development.

Mouse cerberus-like encodes for a secreted factor of the Cerberus/Dan family. This molecule has neural inducing capabilities and can bind to BMP-4 and nodal molecules in the extracellular space. When cerberus-like is inactivated, its function may be compensated for another molecule, since no abnormalities can be observed in the mouse mutant. Compensation mechanisms have been shown to occur between the BMP antagonists chordin and noggin. Here we report the generation of cerberus-like-/-; noggin-/- double mutants to uncover a possible compensation by noggin in cer-l-/- mutant. Double mutants were obtained and failed to show any further detectable defects beside the ones presented by the noggin-/- single mutant. Contrarily to chordin and noggin, mouse cerberus-like and noggin cannot compensate for each other during mouse embryogenesis.

Animals↗
PubMed2000

Value of bronchial artery embolisation with platinum coils in tumorous pulmonary bleeding.

We performed bronchial artery embolizations (BAE) using platinum coils with Dacron fibres in 30 consecutive patients with haemoptysis due to bronchial carcinoma. The aim of the study was to compare immediate results of bleeding cessation, recurrence and survival rates with a historical control group of 15 patients with tumorous pulmonary bleeding who were treated conservatively (non-BAE-group). Bronchial artery embolisation with platinum coils stopped active bleeding in all patients immediately. Comparing the BAE group and controls the cessation of first time haemoptysis (BAE 100% versus non-BAE 93%) and the rates of bleeding recurrence (BAE 50% versus non-BAE 47%) were similar in either group. In case of recurrent bleeding, repeated BAE led to a definite cessation of pulmonary haemorrhage in every case. In contrast, all patients with recurrent haemoptysis without a repeated BAE (8 patients, 27%) and all patients with bleeding recurrence in the non-BAE group died from pulmonary haemorrhage (8 patients, 53%). The mean survival time of the BAE group was significantly longer compared with the non-BAE group, 139 (range: 1-818) days versus 62 (range: 1-186) days (P<0.05). We conclude that consistent BAE proved beneficial in tumorous pulmonary bleeding, particularly with regard to the permanent arrest of haemorrhage in case of recurrence.

Aged↗
PubMed2000

Alpha-2 adrenoceptors are present in rat aorta smooth muscle cells, and their action is mediated by ATP-sensitive K(+) channels.

The role of alpha(2)-adrenoceptors in the response of aorta smooth muscle rings to the alpha(2)-adrenoceptors agonists UK 14,304 and clonidine was studied. Stimulation by 1 - 10 nM UK 14,304 caused dose-dependent relaxant responses in BaCl(2)-contracted endothelium-denuded aorta rings, and hyperpolarization in rings with or without endothelium, which were inhibited by yohimbine and glibenclamide, but not affected by prazosin, propranolol, apamin or iberiotoxin. At higher concentrations (10 nM - 10 microM) UK 14,304 also induced a depolarizing effect which was potentiated by yohimbine and inhibited by prazosin. These results indicate that UK 14,304 acts on alpha(2)-adrenoceptors at lower concentrations and on both alpha(1)- and alpha(2)-adrenoceptors above 10 nM. In rings, with or without endothelium, noradrenaline had a depolarizing effect which was inhibited by prazosin. Adrenaline did not affect the membrane potential but in the presence of prazosin caused hyperpolarization, which was inhibited by yohimbine and glibenclamide. These results indicate that noradrenaline is more selective for alpha(1)-, whereas adrenaline has similar affinities for alpha(1)- and alpha(2)-adrenoceptors. In aortae with endothelium, L-NNA caused a small depolarization but did not affect the hyperpolarization induced by UK 14,304, indicating that NO is not involved in that response. Glibenclamide induced a small depolarization in aortae, with or without endothelium, indicating that ATP-sensitive K(+) channels may play a role in maintaining the smooth muscle's membrane potential. Our results indicate that, in rat aorta, alpha(2)-adrenoceptors are also present in the smooth muscle, and that these receptors act through small-conductance ATP-sensitive K(+) channels.

Adenosine Triphosphate↗
PubMed2000

PEST sequences in cAMP-dependent protein kinase subunits of the aquatic fungus Blastocladiella emersonii are necessary for in vitro degradation by endogenous proteases.

During Blastocladiella emersonii germination, the regulatory (R) and the catalytic (C) subunits of the cAMP-dependent protein kinase (PKA) are rapidly and concurrently degraded, after PKA activation in response to a transient increase in intracellular cAMP levels. The possibility that PEST sequences could be acting as proteolytic recognition signals in this process was investigated, and high score PEST sequences were found in both B. emersonii R and C subunits. Deletions in the PEST sequences were obtained by site-directed mutagenesis and the different PKA subunits were independently expressed in Escherichia coli. Proteolysis assays of the various R and C recombinant forms, using B. emersonii cell extracts as the source of proteases, showed a strong correlation between the presence of high score PEST sequences and susceptibility to degradation. Furthermore, the amino-terminal sequence of the proteolytic fragments indicated that the cleavage sites in both subunits are located at or near the PEST regions. The PEST sequence in B. emersonii C subunit, which when deleted or disrupted leads to resistance to proteolysis, is entirely contained in the 72-amino-acid extension located in the N-terminus of the protein. C subunit mutants carrying deletions in this region displayed little difference in their kinetic properties or enzyme thermostability. These results suggest that the N-terminal extension may only play a role in C subunit degradation.

Amino Acid Sequence↗
PubMed2000

Coronary artery bypass grafts: improved electron-beam tomography by prolonging breath holds with preoxygenation.

In 45 patients with coronary bypass grafts, the breath-hold interval with and that without preoxygenation was measured. Its effect on depiction of the distal graft anastomosis at electron-beam tomography was evaluated. Preoxygenation prolonged the breath-hold interval in most patients, thereby allowing greater anatomic coverage including more distal anastomoses. Preoxygenation may improve scanning of coronary bypass grafts and increase detectability of graft stenoses.

Adult↗
PubMed2000

Abnormal proliferative response of the carotid artery of spontaneously hypertensive rats after angioplasty may be related to the depolarized state of its smooth muscle cells.

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 +/- 1.9 mV) compared to NWR (-69 +/- 1.4 mV), NWR 1K-1C (-60.8 +/- 1.6 mV), WKY (-67.1 +/- 3.2 mV) and WKY 1K-1C (-56.9 +/- 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 +/- 0.86) when compared to arteries of all the other groups (NWR 0.93 +/- 0.65, NWR 1K-1C 1.24 +/- 0.45, WKY 1.22 +/- 0.32, WKY 1K-1C 1.15 +/- 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state.

Analysis of Variance↗
PubMed2000

Cerberus-like is a secreted BMP and nodal antagonist not essential for mouse development.

Mouse cerberus-like (cer-l) is a member of the Cerberus/Dan family of secreted factors. As other members of this family of proteins, Cer-l functions in the extracellular space, inhibiting signaling molecules. Here we show that the neural-inducing and mesoderm-inhibiting activities of Cer-l result from specific binding to BMP and Nodal molecules, respectively. These properties resemble the ones from the related factor Xenopus Cerberus. However, Xenopus Cerberus in addition to BMP4 and Nodal also binds to and inhibits Wnt proteins. We show that Cer-l does not directly inhibit Wnt signals. A null allele of the mouse Cer-l gene was generated by targeted inactivation in ES cells. Homozygous embryos show no anterior patterning defects, are born alive, and are fertile. Since mouse Cer-l and Xenopus Cerberus differ in biochemical activities, we propose the existence of additional members of this family of inhibitors, which may compensate for the loss of cer-l.

Animals↗
PubMed1999

Different pathways for Ca2+ mobilization by angiotensin II and carbachol in the circular muscle of the guinea-pig ileum.

Ca2+ pathways activated by angiotensin II and carbachol were evaluated in the circular muscle of the guinea-pig ileum by recording mechanical and electrical activities. Transient contractions induced by angiotensin II were greatly reduced by Ca2+ removal from the medium whereas carbachol-induced responses were not significantly altered. Nifedipine had no effect on the responses to both agonists. A high concentration of tetrodotoxin (0.1 microM) inhibited angiotensin II-induced contractile responses without affecting the depolarization, whereas 1 mM Ni2+ inhibited the mechanical and electrical effects. Neither tetrodotoxin nor Ni2+ affected carbachol-induced effects. These results indicate that angiotensin II-induced phasic contractions depend on extracellular Ca2+ but not on voltage-dependent L-type Ca2+ channels. It is suggested that angiotensin II activates Ni2+-sensitive Na+ and non-specific cationic channels, whereas the responses to carbachol are dependent on receptor-activated Ca2+ release. Furthermore the different response of the longitudinal and circular muscles to the inhibitory effects of tetrodotoxin and Ni2+ on the angiotensin II- and carbachol-induced contractions indicates that these agonists exert their own myogenic effects on each layer and are able to trigger different Ca2+ mobilization pathways.

Angiotensin II↗
PubMed1999

Comparison of combination of dipyridamole and dobutamine during echocardiography with thallium scintigraphy with thallium scintigraphy to improve viability detection.

The aim of this study was to investigate the relation between radioisotopic and echocardiographic markers of myocardial viability and their correlation with functional recovery after coronary revascularization. Myocardial viability can be detected by techniques exploring various aspects of cell physiology: thallium-201 scintigraphy and dobutamine and dipyridamole echocardiography focus on cell membrane integrity, beta-1 and adrenoceptor, and A2-adenosine receptor-mediated inotropic response, respectively. Fifty-seven patients (mean age 60+/-8 years) with previous myocardial infarction (>3 months), angiographically assessed coronary artery disease, and resting regional dysfunction underwent rest-redistribution 201-thallium scintigraphy and low-dose pharmacologic stress echo with dobutamine (up to 10 microg/kg/min), very low dose regimen of dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine. Criteria for viability in a 13-segment model for both techniques were percent peak activity in redistribution images >55% for thallium-201 and a decrease in wall motion score >1 grade (1 [normal] to 4 [dyskinetic]) for stress echo. Thirty patients underwent coronary revascularization (bypass surgery in 8, angioplasty in 22) and were followed up at 4 weeks from intervention with a resting echocardiogram. The rate of agreement between thallium-201 and stress echo was 63% for dipyridamole, 66% for dobutamine, and 74% for combined dipyridamole-dobutamine (p <0.05 vs dipyridamole and dobutamine). In the 30 patients who underwent revascularization, a regional resting dyssynergy was observed in 225 segments, assuming that postrevascularization functional recovery (which occurred in 126 segments) was the gold standard; combined dipyridamole-dobutamine showed a higher sensitivity (90% confidence interval [CI] 85% to 95%) than thallium-201, dobutamine, or dipyridamole (87%, CI 81% to 92%; 82%, CI 76% to 89%; and 82%, CI 76% to 89%, respectively). Specificity was lower for viability recognition with thallium-201 (61%, CI 51% to 71%) than with dobutamine (93%, CI 88% to 98%), dipyridamole (95%, CI 91% to 99%), and combined dipyridamole-dobutamine (92%; CI 87% to 97%). Combined adrenergic and adenosinergic stimulation recruits an inotropic reserve in a significant proportion of segments with preserved thallium uptake that were nonresponders after either dipyridamole or dobutamine. When functional recovery after successful revascularization is considered as the postoperative gold standard, thallium has a higher sensitivity than dipyridamole or dobutamine; this sensitivity gap is filled with combined dipyridamole-dobutamine. The specificity of all forms of pharmacologic stress echo is better than thallium-201.

Cardiotonic Agents↗
PubMed1999

Pharmacological characterization of RMP-7, a novel bradykinin agonist in smooth muscle.

RMP-7 is a bradykinin (BK) agonist designed to be resistant to kininases such as angiotensin-converting enzyme (ACE). Pharmacological assays were performed with RMP-7 in isolated guinea-pig ileum and rat mesenteric artery. RMP-7 induced contractile responses in the guinea-pig ileum, where the apparent affinity of the peptide (pD2) was significantly lower than that determined for BK (7.3 +/- 0.07 vs. 8.3 +/- 0.05, respectively). HOE-140 blocked this effect indicating that B2 receptor was involved. Captopril (1 microM) had no potentiating effect on RMP-7 but increased pD2 value determined for BK (8.8 +/- 0.1), confirming a high resistance of RMP-7 to the ACE. In rat mesenteric artery, RMP-7 induced endothelium-dependent relaxation (7.8 +/- 0.4), with a higher affinity than that of BK which induced vasodilatation only in the presence of 1 microM captopril (6.9 +/- 0.36). Nevertheless, the maximum effect induced by RMP-7 was lower than that of BK in contrast to that observed in guinea-pig ileum although B2 receptor was involved in both cases. We concluded that: RMP-7 is greatly resistant to the ACE and that the receptor sites activated by RMP-7 and BK show important differences in vascular and non-vascular preparations probably due to the different sensitivity of the B2 receptor to RMP-7.

Animals↗
PubMed1999

Recovery of impaired K+ channels in mesenteric arteries from spontaneously hypertensive rats by prolonged treatment with cholecalciferol.

1. The mechanism responsible for blood pressure reduction in spontaneously hypertensive rats (SHR) after prolonged cholecalciferol treatment was studied. Two-week treatment of SHR with 0.125 mg cholecalciferol kg-1 body weight per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at constant flow. 2. In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca(2+)-dependent K+ channels coupled to alpha 2-adrenoceptors since it was prevented by apamin. 3. The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and their hyperpolarizing responses to alpha 2-adrenergic agonists, which were depressed in untreated SHR. 4. In mesenteric rings with endothelium, alpha 2-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (NWR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while in NWR it was the endothelium-derived hyperpolarizing factor (EDHF). After cholecalciferol treatment, the hyperpolarization induced by alpha 2-adrenergic agonists in SHR smooth muscle cells was mediated by EDHF, as in NWR. 5. Our results indicate that the hypotensive effect of cholecalciferol in the SHR is probably due to the normalization of vascular reactivity, by restoring the functioning of apamin- and ATP-sensitive K+ channels located in the vascular smooth muscle cell membrane, which are impaired in the SHR.

Animals↗
PubMed1999

Chromosomal integration of heterologous DNA in Escherichia coli with precise removal of markers and replicons used during construction.

A set of vectors which facilitates the sequential integration of new functions into the Escherichia coli chromosome by homologous recombination has been developed. These vectors are based on plasmids described by Posfai et al. (J. Bacteriol. 179:4426-4428, 1997) which contain conditional replicons (pSC101 or R6K), a choice of three selectable markers (ampicillin, chloramphenicol, or kanamycin), and a single FRT site. The modified vectors contain two FRT sites which bracket a modified multiple cloning region for DNA insertion. After integration, a helper plasmid expressing the flippase (FLP) recombinase allows precise in vivo excision of the replicon and the marker used for selection. Sites are also available for temporary insertion of additional functions which can be subsequently deleted with the replicon. Only the DNA inserted into the multiple cloning sites (passenger genes and homologous fragment for targeting) and a single FRT site (68 bp) remain in the chromosome after excision. The utility of these vectors was demonstrated by integrating Zymomonas mobilis genes encoding the ethanol pathway behind the native chromosomal adhE gene in strains of E. coli K-12 and E. coli B. With these vectors, a single antibiotic selection system can be used repeatedly for the successive improvement of E. coli strains with precise deletion of extraneous genes used during construction.

Anti-Bacterial Agents↗
PubMed1999

Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis.

OBJECTIVE: The clinical course of fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) may vary considerably from stable condition for years to continuous fatal progression. This prospective study aimed at identifying the prognostic value of bronchoalveolar lavage fluid (BALF) analysis in FASSc. METHODS: Seventy three consecutive patients with SSc and clinical signs of pulmonary involvement were enrolled. Every patient underwent clinical examination, lung function tests, computed tomography (CT), gallium scan, echocardiography, and bronchoalveolar lavage (BAL). Forty nine patients, 26 with pathological and 23 with normal BALF findings were prospectively followed up for two years and re-evaluated annually. RESULTS: At baseline, 51 subjects (70%) showed radiological signs of lung fibrosis and/or alveolitis by CT and diffusion capacity for carbon monoxide (DLco) was decreased in 47 patients (64%). Thirty five patients (48%) had pathological BALF findings. BALF differential counts included BALF granulocytosis in 18, BALF lymphocytosis in 12, and a mixed increase of both granulocytes and lymphocytes in five patients. On follow up, a progression of FA with a significant decrease of DLco was only observed in patients with BALF granulocytosis. In contrast, patients with BALF lymphocytosis or normal BALF cell count had stable lung function parameters during the study period. In none of our patients echocardiography showed evidence of pulmonary hypertension. CONCLUSION: BALF granulocytosis predicts progression of FA with deterioration of lung function, which is most sensitively monitored by DLco. Immunosuppressive treatment is recommended in patients with granulocytic FASSc.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Effect of cholecalciferol treatment on the relaxant responses of spontaneously hypertensive rat arteries to acetylcholine.

We studied the effect of oral cholecalciferol treatment on the endothelium-dependent vascular relaxation and hyperpolarization induced by acetylcholine (ACh), which is impaired in spontaneously hypertensive rats (SHR). Adult female SHR and normotensive Wistar-Kyoto rat (WKY) controls received 125 microg of cholecalciferol per kilogram body weight per day for 6 weeks. The responses to ACh of the isolated mesenteric vascular bed and mesenteric artery rings were measured, as well as the smooth muscle cell membrane potential. After cholecalciferol treatment, the systolic blood pressure and basal perfusion pressure of the mesenteric vascular bed of the SHR fell to control levels. The relaxant and hyperpolarizing effects of ACh, which are reduced in SHR, were also brought to control levels after cholecalciferol treatment. These effects of ACh were inhibited by N(omega)-nitro-L-arginine in SHR and by apamin in WKY. After cholecalciferol treatment, SHR hyperpolarizing responses showed the same inhibition pattern as those of WKY. This indicates that, after cholecalciferol treatment, SHR vascular mesenteric preparation responses to ACh are mediated by endothelium-derived hyperpolarizing factor, which induces activation of Ca(2+)-dependent K(+) channels, as in WKY. In untreated SHR, the ACh-mediated response is entirely due to ACh acting via the release of nitric oxide.

Acetylcholine↗
PubMed1998

Impaired function of alpha-2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats.

The alpha2-adrenoceptor function in mesenteric arteries of spontaneously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations from female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). Resting membrane potential was found to be less negative in mesenteric arteries from SHR than in those from NWR and WKY. Apamin induced a decrease in the membrane potential of mesenteric artery rings without endothelium from NWR and WKY, but had no effects in those from SHR. Both UK 14,304 and adrenaline, in the presence of prazosin, induced a hyperpolarization that was significantly lower in de-endothelialized mesenteric rings from SHR than in those from NWR and WKY. In mesenteric rings with endothelium, however, similar hyperpolarization was observed in the three strains. In NWR mesenteric rings with endothelium the hyperpolarization induced by activation of alpha2-adrenoceptors was abolished by apamin, whereas in intact SHR mesenteric rings this hyperpolarization was slightly reduced by apamin and more efficiently reduced by Nomega-nitro-L-arginine. It is concluded that the activity of potassium channels coupled to alpha2-adrenoceptors is altered in the smooth muscle cells of SHR mesenteric arteries, contributing to their less negative membrane potential. On the other hand, the endothelial alpha2-receptors are functioning in mesenteric vessels from SHR and their stimulation induces a hyperpolarization mainly through the release of nitric oxide.

Adrenergic alpha-Agonists↗