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Biomedical subjects

J E Pinto

Publications and source records attributed to J E Pinto.

At least 19 recordsLinked to original sources

Soluble CD30, dehydroepiandrosterone sulfate and dehydroepiandrosterone in atopic and non atopic children.

Elevated levels of soluble CD30-sCD30 (possibly related to Th2) are seen in atopy and other diseases. Dehydroepiandrosterone (DHEA) may regulate Th1/Th2 balance. The aim was to study the relationship between the levels of sCD30, DHEAS and DHEA in atopic (A) and non atopic (B) children, to assess immune-endocrine interactions. We studied 36 children (8-15 years), 18 (A) monosensitised to Dermatophagoides Pteronyssinus (Dpt.), and 18 (B) with isolate rhinitis (R) or asthma (BA) and R (33.3%) without differences in age and sex. They were all HIV negative and free from any medication. It was determined sCD30, DHEAS and DHEA. There was no statistically significant differences between A and B for the levels of DHEAS, DHEA suggesting that the role of this regulation in Th2 type is not important in patients with allergic disease in this age group. sCD30: A-mean 121.1U/ml; B-mean 53.9U/ml. This difference is statistically significant-p = 0.02. sCD30 in patients only with R showed also significant differences-p = 0.01. These results could reflect the Th2 profile. There is an overlap of the values (for R < 80 U/ml; for BA + R < 140 U/ml). Due to this only values > 80 U/ml for R and > 140 U/ml for BA + R could be considered discriminating for atopy.

Adolescent↗

Methacholine dose-response slopes from maximal bronchial challenge tests in asthmatic children: methodological aspects.

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholine (dose range: 0.097-30.08 mumol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a delta FEV1 > or = 20%; and (2) a MFEV1 > or = 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % delta FEV1 x mumol-1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student's t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 +/- 2.7 delta FEV1%. mumol-1) was 2.88 times higher than DRR50% (31.6 +/- 3.4 delta FEV1%. mumol-1), and the LSS20% (89.1 +/- 2.8% delta FEV1. mumol-1) was 3.10 times higher than LSS50% (28.8 +/- 1.5% delta FEV1. mumol-1). The goodness of fit of LSS50% was significant in all cases, whereas LSS20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

Adolescent↗

ALATOP-RIA in the screening of atopy in a non Caucasian population.

UNLABELLED: ALATOP is an "in vitro" radioimmunoassay screening test for atopy, previously validated in a caucasian population. The aim of the study was to assess the usefulness of a screening test of atopy in a non caucasian population. We select a non caucasian population (n = 208), from hospital immunoallergy consultations, Cape Verde Republic (Africa). It was determined the sensitivity, specificity and predictive values comparing with skin prick tests (SPT) results for the 208 patients, and with clinical data (Clin) in 115 patients. It was also determined the levels of total IgE, done by IRMA. RESULTS: Using different corrections factors, 0.85 gives the best results: ALATOP/SPT-Sensitivity-88.5% +/- 4.34; Specificity-73.8% +/- 8.41; Positive predictive value-66.9%; Negative predictive value-91.4%; Efficiency of the test-79.3%. ALATOP/CLIN-Sensitivity-95.2% +/- 3.89; Specificity-71.2% +/- 12.07; Positive predictive value-65.6%; Negative predictive value-96.2%; Efficiency of the test-80.0%. The mean values of total IgE were-406 IU/ml. CONCLUSIONS: The mean value of total IgE was significantly increased even in the ALATOP-/SPT-not saw in caucasian populations. The use of a different correction factor (0.85) for ALATOP, optimize the test, showing a good negative predictive value, but raises the question of adapted compositions of screening tests for different populations.

Adolescent↗

Extracellular acidification related to the stimulation of catecholamines release by strontium in the bovine adrenal medulla.

The possible modifications of extracellular pH associated with the secretion of catecholamines evoked by the introduction of 2.2 mM Sr2+ to a Ca(2+)-free, buffer-free, Locke solution were investigated in decorticated perfused bovine adrenal glands. A progressive and reversible decrease of external pH accompanied the catecholamine release promoted by Sr(2+)-introduction into the perfusion fluid. This extracellular acid shift was practically undetected when the chromaffin tissue was stimulated by the addition of Sr2+ to a buffered medium. Both the secretory response as well as the extracellular pH drop mediated by Sr(2+)-introduction to a Ca(2+)-free, buffer-free, Locke solution were markedly inhibited by methoxyverapamil (0.3 mM), Mg2+ (20 mM) and hyperosmolarity (750 mOsm). The exposure of the adrenal medulla to a Ca(2+)-free, buffer-free, high-K+ solution containing 2.2 mM Sr2+ for 6 min promoted a significant enhancement of both the secretory response and the acidification of the perfusates compared with the responses evoked by Sr2+ in a 5.6 mM K+ medium. These results are consistent with the existence of a close relationship between extracellular acidification and the release of catecholamines triggered by the introduction of Sr2+ to the perfusion fluid.

Adrenal Medulla↗

Histopathological effects of androgen deprivation in prostatic cancer.

Thanks to earlier detection of clinically significant prostatic adenocarcinoma by measurement of serum prostate-specific antigen (PSA) levels, increasing numbers of patients are undergoing radical prostatectomy. However, the curative potential of this procedure is seriously limited by clinical understaging, which results in positive surgical margins and a marked increase in disease progression. In a multicenter study, histopathologic evaluation of radical prostatectomy specimens showed that presurgical androgen deprivation with leuprolide plus flutamide reduced the incidence of surgical margin involvement by 62%. In patients who received androgen deprivation therapy, characteristic and recognizable histopathologic changes in nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layers, and squamous and transitional cell metaplasia. Androgen deprivation markedly reduced the incidence of prostatic intraepithelial neoplasia (PIN) to 35%. The effects of androgen deprivation on prostatic carcinoma included smaller tumor glands, pyknosis and empty glandular spaces, and vacuolization and degeneration of tumor cells with an inflammatory response. Similar but less pronounced changes with no decrease in PIN were observed in finasteride-treated patients. It is important for pathologists to be aware of these histological changes and process tissue appropriately, because the changes affect the recognition and histological grading of tumors in radical prostatectomy specimens.

Adenocarcinoma↗

Effect of hyperosmolarity on extracellular acidification associated with catecholamine secretion evoked by barium in perfused bovine adrenal medulla.

1. The effects of the increase of osmotic strength on extracellular pH modifications produced during buffer-free, 5 mM Ba2+ stimulation was studied in decorticated perfused bovine adrenal glands. 2. A pronounced and reversible attenuation of the extracellular pH drop as well as of the release of catecholamines induced by Ba2+ was detected in glands exposed to a hyperosmotic (750 mOsm) perfusion fluid made up by the addition of NaCl. 3. Similar results were observed using sucrose as osmoticant instead of NaCl. 4. A progressive decline in both external acidification and secretory response to Ba2+ was found on gradually increasing the osmotic strength of the perfusion fluid. 5. These results provide additional evidence in favour of the existence of a close association between extracellular acidification and adrenomedullary secretion induced by buffer-free Ba2+.

Adrenal Medulla↗

Quantitative skin prick tests and specific IgE (CAP System) for D. pteronissynus--correlation of results in a paediatric population.

The CAP System compared with RAST has a greater sensitivity, with the same specificity, as well as an excellent correlation with skin prick tests (SPT), as documented by others. Standardization of SPT is essential for routine and investigational purposes. We used a standardized lancet (DHS), and the methodology of reading the SPT was a computerized digitalized graphics tablet coupled to an IBM-PC AT using CAD software, expressing the result as wheal areas with cut off +/- at 7 mm2. The method is precise and reproducible with a mean coefficient of variation (cv) intratester--T1: 3.1%, T2: 3.5% and a cv intertester: 2.93%. We compare the results of SPT of two different allergen extracts for Dermatophagoides Pteronissynus (DPt) (Bencard; Merck/Allergo-Pharma, standardized in SBU) and correlate them with specific IgE, in 122 patients, 72 males and 50 females, aged 3 to 19 years. The results between the extracts and the results of specific IgE obtained by CAP System with each of the extracts, were correlated. 34 patients were considered to be non atopic. 88 patients showed at least one positive result with one test, being those used to correlate the positive results.... The results showed good correlations for quantitative SPT between Bencard and Merck/Allergo-Pharma, as well as for the capacity of eliciting positive results. When SPT were compared to specific IgE as +/- and as quantitative results, there were good correlation for Bencard/CAP and Merck/CAP. The results obtained suggest that CAP can be used to validate allergen extracts of DPt and that studies with other extract are advisable.

Adolescent↗

ALATOP:sensitivity, specificity and predictive value of a new "in vitro" screening test of atopy.

UNLABELLED: The limitations of total IgE for the screening of atopy, gave rise to in vitro multispecific IgE tests to common allergens. These should have an increased sensitivity and specificity when compared to total IgE. Previous data showed the interest of such tests in screening procedures. ALATOP is a new in vitro multispecific IgE test including common aero and food allergens, in liquid phase, for paediatric and adult population. The result is expressed only in positive/negative. The aim of the study was to determine the sensitivity, specificity, positive and negative predictive value and test efficiency, by comparing the results obtained in 266 paediatric patients (selected in our Unit based on a good correlation between clinical history and skin prick tests--SPT), between ALATOP and SPT. RESULTS: 1) Sensitivity: 89.57%; 2) Specificity: 98.06%; 3) Positive predictive value: 98.65%; 4) Negative predictive value: 85.59%; 5) Efficiency of the test: 92.86%; 6) Reproducibility of the test--average: 5.63%. Based on this results and when they are compared to single specific IgE determinations, that are assumed to be about 80% of the sensitivity of SPT, ALATOP showed excellent results, allowing its use in the screening of atopic disease.

Adolescent↗

Decrease of extracellular pH associated with the secretion of catecholamines induced by barium in perfused bovine adrenal medulla.

1. The possible modifications of extracellular pH produced during buffer-free 5 mM Ba2+ stimulation was studied in decorticated perfused bovine adrenal glands. 2. A significant and reversible drop of pH accompanied the release of catecholamines each time the tissue was exposed to a buffer-free 5 mM Ba2+ solution. 3. A progressive declination of the magnitude of this acidification associated with a gradual attenuation of the secretory response was observed consecutive to successive periods of Ba(2+)-stimulation. 4. D-600 (methoxyverapamil), in a concentration of 3 x 10(-4) M, markedly antagonized both Ba(2+)-induced secretory response and extracellular pH drop. 5. Perfusion of adrenal medulla for 4 min period with Locke solution buffered at pH 6.9, significantly and reversibly reduced the secretory response to 5 mM Ba2+ (pH 6.9) compared to a first control response obtained 35 min before at pH 7.4. 6. These results are compatible with the view that Ba(2+)-induced secretory activity is accompanied by the release of protons which could be involved in a local negative automodulatory mechanism of adrenomedullary secretion.

Adrenal Medulla↗

Comparison of acute effects of mitoxantrone and doxorubicin in guinea-pig atria.

1. The acute effects of doxorubicin (DOX) and mitoxantrone (MTX) on basal rate and on positive chronotropic activity induced by 1-noradrenaline (1-NA) were investigated in isolated guinea-pig atria. 2. DOX (10(-5)-10(-4)M) progressively depressed atrial rate after a short latency period. Only 10(-4) M MTX reduced the spontaneous frequency after 120 and 180 min incubation. This effect was significantly lower to that elicited by DOX (10(-4)M). 3. Atropine (1.5 x 10(-6) M) and reserpine pretreatment did not affect the negative chronotropic action induced by DOX or MTX. 4. DOX (10(-5)-10(-4) M) produced a significant reduction of the maximal chronotropic response (Emax) to 1-noradrenaline (1-NA) after 60, 120 and 180 min of exposure. 5. MTX (10(-5)-10(-4) M) after 60 and 120 min incubation induced a beta-adrenergic, concentration- and time-dependent, competitive blocking effect. After 180 min of exposure, MTX (10(-4) M) reduced the Emax to 1-NA which was of less magnitude to that produced by DOX (10(-4) M). 6. Although both DOX and MTX depressed spontaneous and 1-NA induced chronotropic activity, MTX effects were of a slower onset and development compared to those exerted by DOX.

Animals↗

Enhanced angiotensin converting enzyme binding in arteries from spontaneously hypertensive rats.

AIM: To localize and measure angiotensin converting enzyme (ACE) in different vascular beds of genetically hypertensive rats. METHODS: Quantitative autoradiography using the angiotensin converting enzyme (E.C. 3.4.15.1) inhibitor [125I]351A. RESULTS: [125I]351A binding was significantly increased in the ascending aorta (both adventitia and intima), descending (abdominal) aorta, carotid artery and coronary arteries of adult, 12-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. Increased [125I]351A binding was also present in the descending aorta of 1-week-old SHR compared with age-matched WKY rats, and both groups of young rats had much higher binding than adult rats. No difference in [125I]351A binding was found in the caudal (tail) artery of adult SHR compared with WKY rats. In both the atria and the ventricles of adult SHR, [125I]351A binding was very significantly reduced. CONCLUSIONS: Our results indicate that higher ACE concentrations occur in some arteries of genetically hypertensive rats, and support the hypothesis that local arterial concentrations of ACE affect the development and maintenance of genetic hypertension.

Animals↗

Estrogens regulate angiotensin-converting enzyme and angiotensin receptors in female rat anterior pituitary.

We studied the effects of the estrous cycle, ovariectomy and estrogen replacement on angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) and angiotensin II (AT) receptors in the pituitary gland of the female rat. Quantitative autoradiography, with the use of consecutive pituitary sections, allowed for simultaneous determination of changes in binding and in the potential AT synthetic ability of individual pituitaries, and for a correlation between these two phenomena. In the anterior pituitary, ACE activity and binding of the ACE inhibitor [125I]-351A were not changed during the estrous cycle. Ovariectomy produced a significant increase in ACE activity and binding, and both of these parameters returned to normal after estrogen replacement. There were no changes in ACE activity or binding in the posterior pituitary during the estrous cycle or after ovariectomy or hormone replacement. AT receptors were characterized as of the AT1 type, since they were displaced by the selective AT1 antagonist DuP 753 and not by the AT2 competitor PD 123177. There were marked changes in the concentration of AT1 receptors during the estrous cycle, with highest numbers in metestrus, lower in estrus and diestrus, and lowest during proestrus. Estrogen replacement in ovariectomized rats decreased AT1 receptor number in the anterior pituitary. Our results indicate a dual effect of estrogen on anterior pituitary AT, physiologically on AT receptor expression and pharmacologically on ACE activity.

Angiotensin II↗

Increased beta 2-adrenoceptors in the superior cervical ganglia of genetically hypertensive rats.

[125I]Iodocyanopindolol binding sites were characterized by autoradiography in the superior cervical ganglia of Wistar-Kyoto (WKY) rats. A high concentration of (-)-[125I]iodocyanopindolol binding sites, characterized as beta-adrenoceptors by (-)-propranolol displacement, was distributed throughout the ganglia and in the postganglionic (internal carotid) nerve. ICI 118,551, a beta 2-selective antagonist, displaced more than 85% of the binding sites, whereas CGP 20712A, a beta 1-selective antagonist, displaced less than 10% of the binding sites, indicating that the beta-adrenoceptors were primarily of the beta 2-subtype. Emulsion autoradiography demonstrated that at least part of the binding sites were associated with principal ganglion cells. Unilateral deafferentation did not modify the number of binding sites in the superior cervical ganglia of WKY or spontaneously hypertensive rat (SHR). These results suggest that at least part of these receptors may correspond to prejunctional beta 2-adrenoceptors originated in principal ganglion cells. The concentration of beta 2-receptors was increased in the superior cervical ganglia of young and adult SHR when compared to age-matched WKY rats (49% and 39%, respectively). There were no differences in beta 2-adrenoceptor number in the stellate ganglia of young and adult WKY and SHR. These results suggest that beta 2-adrenoceptor stimulation may be selectively enhanced in some peripheral sympathetic ganglia in SHR and this could play a role in the development and maintenance of the increased sympathetic activity in this strain.

Adrenergic beta-Antagonists↗

Autoradiographic localization and quantification of rat heart angiotensin converting enzyme.

Quantitative autoradiography with the angiotensin converting enzyme inhibitor [125I]351A revealed the presence of specific binding for this enzyme in the valve leaflets of the rat heart and in the aortic wall. Branches of the coronary arteries showed binding localized throughout the arterial walls. Binding was also present in the heart atria, where it was four-fold higher than in the heart ventricles. These results support the hypothesis of a physiologic role for angiotensin converting enzyme in peptide metabolism in specific heart structures.

Animals↗

Increased beta 2-adrenoceptor number in peripheral sympathetic ganglia of spontaneously hypertensive rats.

We determined beta-adrenoceptor concentrations in sympathetic ganglia from adult Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Adjacent tissue sections were incubated with [125I]iodocyanopindolol, with or without excess of unlabeled (-)-propranolol, the beta 1-antagonist CGP 20712A or the beta 2-antagonist ICI 118,551. Most beta-adrenoceptors were of the beta 2-type. Their concentration was higher in the superior cervical and stellate ganglia of SHR when compared to normotensive WKY. Our results indicate that beta 2-adrenoceptor stimulation may be enhanced in sympathetic ganglia of SHR, and could play a role in the maintenance of their increased sympathetic activity.

Animals↗

Specific insulin binding sites in snail (Helix aspersa) ganglia.

1. Insulin binding sites were characterized and quantified in snail (Helix aspersa) ganglia by incubation of tissue sections with 125I-porcine insulin, autoradiography with [3H]Ultrofilm, image analysis coupled to computer-assisted microdensitometry, and comparison with 125I-standards. Cellular localization was performed in the same sections by emulsion autoradiography. 2. Specific insulin binding sites were demonstrated in discretely localized groups of neurons of the cerebral, pleural, parietal, visceral, and pedal ganglia and in nerves. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity insulin binding sites (Kd, 0.13 +/- 0.01 nM; Bmax, 157 +/- 10 fmol/mg protein). 3. Our results suggest that insulin may play a role as a neurotransmitter or neuromodulator in snail ganglia.

Animals↗

Angiotensin II binding sites in the superior cervical ganglia of spontaneously hypertensive and Wistar-Kyoto rats after preganglionic denervation.

In the superior cervical ganglia (SCG) binding site density of angiotensin II (ANG II) was higher in adult spontaneously hypertensive rats (SHR) (571 +/- 29 fmol/mg protein) compared to that in the adult Wistar-Kyoto rat (WKY) (375 +/- 9 fmol/mg protein, P less than 0.05). The ANG II binding density was significantly decreased in the SCG of SHR (-59%, P less than 0.01) and of WKY (-39%, P less than 0.05) after unilateral preganglionic denervation (operated v sham-operated ganglia). Part of the binding sites in the superior cervical ganglia may be present in or be associated to preganglionic nerves, and the number of these sites is higher in SHR.

Angiotensin II↗

Autoradiographic characterization of beta-adrenoceptors in rat heart valve leaflets.

beta-Adrenoceptors were localized and characterized in valve leaflets of the rat heart. Sixteen micrometer-thick tissue sections containing the mitral and aortic valves were incubated with (-)3-[125I]iodocyanopindolol followed by autoradiography with computerized microdensitometry and comparison with 125I-labeled standards. beta-Adrenoceptors were present in all the valves studied. The selective beta 1-adrenoceptor antagonist CGP 20712 A (100 nM) displaced not more than 20% of the total binding sites, suggesting that most of the beta-adrenoceptors in the valve leaflets are of the beta 2-subtype. Forskolin-binding sites were detected in the mitral valve leaflet by incubation of adjacent tissue sections with [12-3H]forskolin. Our results indicate that catecholamines could regulate the function of the heart valves through stimulation of beta 2-adrenoceptors.

Animals↗