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Biomedical subjects

F Costa

Publications and source records attributed to F Costa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans.

It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.

Adenosine↗
PubMed2000

Interaction of carbon dioxide and sympathetic nervous system activity in the regulation of cerebral perfusion in humans.

Recent studies suggest that activation of the sympathetic nervous system either directly or indirectly influences cerebrovascular tone in humans even within the autoregulatory range. In 6 healthy subjects (aged 29+/-4 years), we used transcranial Doppler sonography to determine cerebral blood flow velocity during sympathetic activation elicited through head-up tilt (HUT) and sympathetic deactivation through ganglionic blockade. PaCO(2) was manipulated through hyperventilation and CO(2) breathing (5%). With subjects in the supine position and during HUT, mean arterial pressure was not influenced by PaCO(2). During ganglionic blockade, mean arterial pressure decreased markedly with hyperventilation (-13+/-1.9 mm Hg). Manipulation of sympathetic tone elicited only mild changes in cerebral blood flow (64+/-5.8 cm/s supine, 58+/-4.9 cm/s upright, and 66+/-6.2 cm/s during ganglionic blockade; P:=0.07 by ANOVA). The slope of the regression between PaCO(2) and mean velocity was 1.6+/-0.18 cm/(s. mm Hg) supine, 1.3+/-0.14 cm/(s. mm Hg) during HUT, and 2.3+/-0.36 cm/(s. mm Hg) during ganglionic blockade (P:<0.05). Spontaneous PaCO(2) and ventilatory response to hypercapnia were also modulated by the level of sympathetic activity. Changes in sympathetic tone have a limited effect on cerebral blood flow at normal PaCO(2) levels. However, the sympathetic nervous system seems to attenuate the CO(2)-induced increase in cerebral blood flow. This phenomenon may indicate a moderate direct effect of the sympathetic nervous system on the cerebral vasculature. Furthermore, sympathetic activation tends to increase ventilation and thus can indirectly increase cerebrovascular tone.

Adult↗
PubMed2000

Gender-related differences in counterregulatory responses to antecedent hypoglycemia in normal humans.

Compared to men, inherent counterregulatory responses are reduced in healthy and type 1 diabetic women. Despite this, the prevalence of hypoglycemia in patients with type 1 diabetes (type 1 DM) is gender neutral. The aim of this study was to determine the in vivo mechanism(s) responsible for this apparent clinical paradox. The central importance of antecedent hypoglycemia in causing subsequent counterregulatory failure is now established. We, therefore, hypothesized that a gender-related difference to the blunting effects of prior hypoglycemia may exist, and this could explain why type 1 DM women do not have an increased prevalence of hypoglycemia despite reduced counterregulatory responses. Fifteen healthy male and female individuals (eight men and seven women) underwent four separate 2-day experimental protocols in a randomized fashion. Day 1 involved identical morning and afternoon 2-h hyperinsulinemic (9 pmol/kg x min) glucose clamp studies with 5.1 +/- 0.1, 3.9 +/- 0.1, 3.3 +/- 0.1, or 2.9 +/- 0.1 mmol/L. Day 2 consisted of a single 2-h hypoglycemic clamp of 2.9 +/- 0.1 mmol/L. Insulin levels were similar on both days of each protocol in men and women. After day 1 euglycemia (5.1 +/- 0.1 mmol/L), day 2 counterregulatory responses were significantly increased (P < 0.01) in men relative to women. In women, counterregulatory responses were resistant to the effects of day 1 hypoglycemia. Antecedent hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L produced 3 +/- 2%, 5 +/- 2%, and 25 +/- 4% aggregate reductions in day 2 neuroendocrine, muscle sympathetic nerve activity, and metabolic counterregulatory responses. In marked contrast, identical day 1 hypoglycemia of 3.9, 3.3, and 2.9 +/- 0.1 mmol/L in men produced significantly greater reductions in day 2 counterregulatory responses of 30 +/- 6%, 39 +/- 6%, and 52 +/- 6%, respectively. The net effect of the differential gender effects of antecedent hypoglycemia was to overcome the usually increased (50%) sympathetic nervous system (SNS) counterregulatory responses to hypoglycemia found in men. We conclude that 1) antecedent hypoglycemia produces less blunting of counterregulatory responses to subsequent hypoglycemia in women relative to men; 2) two episodes of antecedent hypoglycemia can overcome the greater SNS response to hypoglycemia usually found in men; and 3) the reduced susceptibility of women to the blunting effects of antecedent hypoglycemia may be the mechanism explaining why, despite inherently reduced SNS counterregulatory responses, female type 1 DM patients have a similar prevalence of hypoglycemia compared to men.

Activity Cycles↗
PubMed2000

Hypoglycemic counterregulatory responses differ between men and women with type 1 diabetes.

The aim of this study was to determine whether sex-related differences occur in counterregulatory responses to hypoglycemia in adult type 1 diabetic patients. Experiments were carried out on 16 (8 men/8 women) type 1 diabetic patients and compared with 16 (8 men/8 women) age- and weight-matched normal individuals. Men and women with type 1 diabetes were matched for age (26+/-2 vs. 25+/-1 years), duration of diabetes (9+/-1 vs. 8+/-1 years), glycemic control (HbA1c 7.7+/-0.3 vs. 7.8+/-0.2%), and weight (BMI 22.8+/-1 vs. 22.1+/-1 kg/m2), respectively. After normalizing plasma glucose overnight, patients underwent a 2-h hyperinsulinemic-hypoglycemic clamp study. Plasma glucose (3.0+/-0.1 mmol/l) and insulin (510+/-48 pmol/l) levels were equated in all groups. Plasma epinephrine, norepinephrine, growth hormone (GH), muscle sympathetic nerve activity (MSNA), and endogenous glucose production (EGP) responses were significantly lower (P<0.01) in type 1 diabetic women compared with men. Autonomic symptom scores, lipid oxidation, nonesterified fatty acids (NEFAs), and glycerol responses were equivalent between men and women with type 1 diabetes despite significantly reduced sympathoadrenal and MSNA responses in women. Autonomic nervous system (ANS) and EGP responses were equivalent in type 1 diabetic and normal individuals. However, lipid oxidation (assessed by indirect calorimetry), glycerol, and NEFA responses were increased (P<0.01) in type 1 diabetic patients compared with normal control subjects. We conclude that counterregulatory responses to fixed hypoglycemia differ markedly in men and women with type 1 diabetes: 1) sympathetic nervous system, GH, and EGP responses are significantly reduced in type 1 diabetic women, 2) autonomic symptom awareness and lipolytic responses appear to be relatively increased in type 1 diabetic women compared with men, and 3) during conditions of similar hyperinsulinemic hypoglycemia and ANS drive, lipid oxidation and lipolytic responses can be increased in type 1 diabetic patients compared with normal individuals.

Adult↗
PubMed2000

Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans.

The aim of this study was to determine whether the duration of antecedent hypoglycemia regulates the magnitude of subsequent counterregulatory failure. A total of 31 lean healthy overnight-fasted individuals (16 men/15 women) were studied. There were 15 subjects (8 men/7 women) who underwent two separate 2-day randomized experiments separated by at least 2 months. On day 1, 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1)) euglycemic (5.2 +/- 0.1 mmol/l) or hypoglycemic (2.9 +/- 0.1 mmol/l) glucose clamps (prolonged hypoglycemia) were carried out in the morning and afternoon. Of the other subjects, 16 participated in a 2-day study in which day 1 consisted of morning and afternoon short-duration hypoglycemia experiments (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 5 min), and 10 of these individuals underwent an additional 2-day study in which day 1 consisted of morning and afternoon intermediate-duration hypoglycemia (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 30 min). The next morning (day 2) all subjects underwent an additional 2-h hyperinsulinemic-hypoglycemic clamp (2.9 +/- 0.1 mmol/l). The rate of fall of glucose (0.07 mmol/min) was carefully controlled during all hypoglycemic studies so that the glucose nadir was reached at 30 min. Despite equivalent day 2 plasma glucose and insulin levels, there were significant differences in counterregulatory physiological responses. Steady-state epinephrine, glucagon, growth hormone, cortisol, and pancreatic polypeptide levels were similarly significantly blunted (P < 0.01) by the differing duration day 1 hypoglycemia compared with day 1 euglycemia. Muscle sympathetic nerve activity and endogenous glucose production were also similarly blunted (P < 0.01) by day 1 hypoglycemia (relative to day 1 euglycemia). Day 2 hypoglycemic symptoms were significantly reduced (P < 0.01) after day 1 prolonged intermediate- but not short-duration hypoglycemia. In summary, two episodes of short-duration moderate hypoglycemia can produce significant blunting of key neuroendocrine and metabolic counterregulatory responses. Hypoglycemic symptom scores are reduced by prolonged but not short-duration prior hypoglycemia. We conclude that in healthy overnight fasted humans, 1) neuroendocrine, autonomic nervous system, and metabolic counterregulatory responses are sensitive to the blunting effects of even short-duration prior hypoglycemia, and 2) the duration of antecedent hypoglycemia results in a hierarchy of blunted physiological responses with hypoglycemic symptom awareness less vulnerable than neuroendocrine responses.

Adult↗
PubMed2000

Stability of Le Fort I osteotomy in maxillary inferior repositioning: review of the literature.

Inferior repositioning of the maxilla to correct vertical maxillary deficiency has been one of the more unstable orthognathic procedures performed. This kind of maxillary movement is the logical correction of short face syndrome due to maxillary vertical deficiency, but in spite of the esthetic improvement that it produces, a great tendency to relapse was observed. Unfortunately, the procedure is relatively rare, and this is reflected in the small sample of the studies. The literature concerning the stability of Le Fort I osteotomy in maxillary inferior repositioning was reviewed to analyze and discuss the stability of the surgical techniques proposed.

Animals↗
PubMed1999

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Adult↗
PubMed1999

Impaired T-cell regulation of B-cell growth in Helicobacter pylori--related gastric low-grade MALT lymphoma.

BACKGROUND & AIMS: Neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma are responsive to T helper cells and sensitive to withdrawal of H. pylori-induced T-cell help. METHODS: The clonal progeny of T cells from the gastric mucosa of 5 patients with MALT lymphoma was compared with that of T-cell clones obtained from 5 H. pylori-infected patients with chronic gastritis. RESULTS: T-cell clones were assessed for specificity to H. pylori, cytokine profile, help for B-cell proliferation, and perforin- or Fas-mediated cytotoxic regulation of B-cell growth. Twenty-eight of 165 CD4(+) gastric clones from MALT lymphoma and 33 of 178 CD4(+) clones from chronic gastritis recognized H. pylori antigens. Cytokine production was similar in the 2 series of clones. All MALT lymphoma-derived clones dose-dependently increased their B-cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1 because of concomitant cytolytic killing of B cells. T-cell clones from MALT lymphoma had both reduced perforin-mediated cytotoxicity and poor ability to induce Fas-mediated apoptosis. These defects were limited to gastric T cells. CONCLUSIONS: H. pylori-induced T cell-dependent B-cell activation and deficient cytotoxic control of B-cell growth may link H. pylori infection, local T-cell response, and genesis of low-grade gastric MALT lymphoma.

Aged↗
PubMed1999

Helicobacter pylori stool antigen test: clinical evaluation and cost analysis of a new enzyme immunoassay.

Noninvasive tests for Helicobacter pylori are increasingly used. Recently, an enzyme immunoassay for H. pylori detection in feces has been put on the market. Aim of this multicenter study was to evaluate the usefulness of this novel test as a predictor of H. pylori status in the pretreatment setting. Three hundred consecutive patients were enrolled. None of the patients had received any eradicating treatment in the last 12 months, and all underwent gastroscopy with biopsies of the antrum and body for histology (H) and rapid urease test (RUT). H. pylori status was defined positive (or negative) if both H and RUT were positive (or negative). When H and RUT gave conflicting results, the patients were classified as H. pylori-indeterminate. A stool specimen was collected for each patient and tested by using a novel enzyme immunoassay for H. pylori detection (HpSAT). Sensitivity, specificity, and diagnostic accuracy of the test were calculated, as was the cost of each assay. H. pylori status was positive in 159 patients, negative in 131, and indeterminate in 10. HpSAT gave evaluable results (positive or negative) in 293 patients, and doubtful results in 7 (2.3%). Sensitivity, specificity, and diagnostic accuracy of HpSAT were 96.8%, 89.7%, and 93.6% respectively. Considering the H. pylori-indeterminate patients as positive, the percentages were 95.8%, 98.7%, and 93.2% respectively. The cost for each assay was about US $27. These results suggest that HpSAT is a noninvasive, simple, reliable, fast, and cheap method for evaluating H. pylori status in the pretreatment setting.

Antigens, Bacterial↗
PubMed1999

Comparison of antibody and protective immune responses against Trypanosoma cruzi infection elicited by immunization with a parasite antigen delivered as naked DNA or recombinant protein.

Immunization with naked DNA represents an attractive strategy for development of vaccines against a variety of infections including those caused by protozoan parasites. Recently, we have described that immunization with a plasmid containing the trans-sialidase (TS) gene induced protective immunity against Trypanosoma cruzi infection in BALB/c mice. The present study was aimed at examining and comparing the effectiveness of immunization using either plasmid or recombinant delivered antigens in a mouse strain highly susceptible to infection (A/Sn). Two plasmids were generated containing the coding region for the catalytic domain of TS. TS gene was inserted into pcDNA3 vector with or without the coding region for TS signal peptide. These two plasmids were found to be equally immunogenic at inducing antibodies to TS or inhibition of T. cruzi infection. A third plasmid, in which the TS gene was inserted into the vector VR1012, was as immunogenic as the two others. Immunization with a TS recombinant protein in alum generated a significantly higher antibody response as measured by ELISA or inhibition of TS enzymatic activity. Most relevant, this immunization reduced the mortality due to acute infection.

Animals↗
PubMed1999

Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization with a DNA vaccine containing a Trypanosoma cruzi gene.

Immunization with a plasmid DNA containing the gene encoding the catalytic domain of trans-sialidase (TS) elicits protective immune responses against experimental Trypanosoma cruzi infection. As several studies provided strong evidence that during infection CD4 Th1 and CD8 T cytotoxic type 1 (Tc1) cells are important factors in host resistance, the present study was designed to evaluate which T-cell types were activated in DNA-vaccinated BALB/c mice. We found that bulk cells from DNA-immunized mice had CD4 and CD8 T cells that produced gamma interferon (IFN-gamma) but not interleukin-4 (IL-4) or IL-10. To characterize the TS-specific T cells at the clonal level, we generated CD4 and CD8 clones. We obtained cytotoxic CD4 clones of the Th1 type that secreted large amounts of IFN-gamma but not IL-4 or IL-10. Unexpectedly, we obtained other CD4 clones with a Th2 phenotype, secreting IL-4 and IL-10 but not IFN-gamma. All CD8 clones were cytotoxic and produced IFN-gamma. IL-4 and IL-10 were not secreted by these cells. Using synthetic peptides, we determined a CD8 epitope recognized by several clones as being represented by amino acids IYNVGQVSI. The antiparasitic activity of a CD4 Th1 and a CD8 Tc1 clone was assessed in vitro. CD4 or CD8 T cells significantly inhibited T. cruzi development in infected macrophages or fibroblasts, respectively. We concluded that DNA vaccine efficiently generates potentially protective CD4 Th1 and CD8 Tc1 cells specific for a T. cruzi antigen, therefore reinforcing the possibility of using this strategy for developing a preventive or therapeutic vaccine against Chagas' disease.

3T3 Cells↗
PubMed1999

Intravascular source of adenosine during forearm ischemia in humans: implications for reactive hyperemia.

It is believed that adenosine is released in ischemic tissues and contributes to reactive hyperemia. We tested this hypothesis in the human forearm using microdialysis to estimate interstitial and intravascular levels of adenosine and caffeine withdrawal to potentiate endogenous adenosine and determine its effect on reactive hyperemia. Forearm blood flow response to ischemia was measured by air plethysmography before and 60 hours after the last dose of caffeine (250 mg TID for 7 days, n=6). Forearm blood flow increased by 274+/-66% and 467+/-97% after 3 minutes of forearm ischemia, before and during caffeine withdrawal, respectively (P<0.05). Thus, caffeine withdrawal enhances reactive hyperemia. To determine the source of adenosine, we measured interstitial adenosine with the use of a microdialysis probe inserted into the flexor digitorum superficialis muscle of the forearm, and we measured intravascular adenosine with the use of a microdialysis probe inserted retrogradely into the medial cubital vein. Dialysate samples were collected at 15-minute intervals during resting, forearm ischemia, and recovery periods. Forearm ischemia failed to increase muscle dialysate concentrations of adenosine but did increase intravascular dialysate adenosine 2.1-fold, from 0.61+/-0.12 to 1.28+/-0.39 micromol/L (P<0.01, n=8). Intravascular dialysate concentrations of thromboxane B2 did not increase during ischemia, ruling out platelet aggregation as a source of adenosine. These results support the hypothesis that endogenous adenosine contributes to reactive hyperemia and indicate that the major source of adenosine in the human forearm is intravascular. We speculate that endothelial cells are the source of intravascular adenosine during ischemia.

Adenosine↗
PubMed1999

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection.

Trypanosoma cruzi. the protozoan parasite that causes Chagas' disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas' disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-gamma-producing T cells.

Animals↗
PubMed1999

Stability of Le Fort I osteotomy in maxillary advancement: review of the literature.

Stability of the skeletal segments repositioned during orthognathic surgery is still a concern in maxillofacial surgery. In an attempt to establish a consensus about one of the most frequently performed repositioning surgeries, the literature from 1985 to 1999 concerning stability of Le Fort I osteotomy in maxillary advancement was reviewed. There have been many problems in interpreting the results of the analysis because of differences in the design of the studies and the multifactorial nature of the disorder. For this reason each problem that emerged in the literature is analyzed and discussed.

Humans↗