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Biomedical subjects

M Castellano

Publications and source records attributed to M Castellano.

At least 109 records · Page 6Linked to original sources
PubMed1992

Determination of heavy metals in human liver.

The levels of Cr (2.49 +/- 0.89 ppm), Mn (5.08 +/- 1.60 ppm), Ni (1.81 +/- 0.95 ppm) and Pb (4.43 +/- 3.12 ppm) were measured in dessicated liver from 44 cases of sudden traumatic death considered as representative of the general population in our area, after ruling out the presence of any underlying disease. Atomic absorption spectrophotometry and electrothermal atomization was carried out after hot, acid digestion, of the dessicated samples. After cancelling the influence of age and cause of death, a significant, positive correlation between Cr/Mn (P = 0.0009; R = 0.493) and Cr/Ni (P = 0.0245; R = 0.347) levels was found.

Adult↗
PubMed1992

Antidiuretic hormone and atrial natriuretic peptide during lower body negative or positive pressure in hypertensive patients with and without left ventricular hypertrophy.

Aim of the study was to evaluate the effect of cardiopulmonary receptors activation and deactivation on antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) incretion in hypertensive and normotensive subjects. Twenty-one male subjects, 7 normotensives and 14 mild hypertensives, 7 without and 7 with left ventricular hypertrophy (LVH) were admitted to the study. Each subject underwent selective loading and unloading of cardiopulmonary receptors, by application of a positive (LBPP) or negative (LBNP) pressure to the lower body. Blood samples were taken for measurement of ANP, ADH, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. ADH plasma concentration increased during cardiopulmonary receptors inhibition, but this increase became statistically significant (p less than 0.05) at a step of LBNP (-40 mm Hg), in which an involvement of the sinoaortic receptors cannot be excluded. ANP plasma levels increased progressively during LBPP (p less than 0.05 at least). These changes were significantly reduced in hypertensive patients with LVH.

Adolescent↗
PubMed1992

Reduction of left ventricular hypertrophy after longterm antihypertensive treatment with doxazosin.

The aim of this study was to evaluate the effect of antihypertensive treatment with doxazosin on left ventricular anatomy and function. Therefore, after 4 weeks of washout with placebo (phase 1), doxazosin (dosage range from 1 to 16 mg, plus hydrochlorothiazide when necessary) was given to 11 essential hypertensive patients (6 M, 5 F, age range 34-63 years) for 8 weeks (phase 2) in order to achieve diastolic blood pressure values less than 90 mmHg; this dosage was then maintained for a further 20 weeks up to the end of the study (phase 3). Blood pressure was significantly reduced (Anova P less than 0.05), while heart rate did not change. A significant reduction of left ventricular mass index (from 128.5 +/- 26 to 114 +/- 23 g/m2, at the end of phase 1 and 3 respectively, P less than .001)) was observed. Before and during treatment left ventricular systolic function, both at rest and during stress (handgrip and cold pressor tests), evaluated by fractional shortening as related to end-systolic stress, in every case within 95% confidence limits, was calculated in normal subjects. Diastolic function, as evaluated by the ratio between peak early and atrial velocities of transmitral flow examined by pulsed doppler was significantly improved. Plasma catecholamine concentrations, plasma renin activity and plasma aldosterone did not change. A significant reduction of plasma cholesterol concentration was observed. These results confirm that doxazosin is a well tolerated and effective antihypertensive drug, with a favourable effect on blood lipids and they indicate that its longterm administration can induce a significant reduction of left ventricular mass.

Adrenergic alpha-Antagonists↗
PubMed1991

Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in human hematopoietic cells.

The steady-state expression of three members of the myb family of genes, c-myb, B-myb, and A-myb, was studied in four purified normal human hematopoietic cell types, ie, T and B lymphocytes, monocytes, and granulocytes. The c-myb proto-oncogene is low to undetectable in resting T and B lymphocytes and shows a biphasic induction in both cell types after mitogenic stimulation, with a first peak at 3 hours and a second and stronger induction at 44 to 72 hours. Study of the B-myb gene showed that this gene is low to undetectable in resting T or B cells and is strongly induced after mitogenic stimulation with a peak between 44 and 72 hours in both cell types. Finally, the A-myb gene shows a pattern of expression in lymphocytes different from that of c-myb and B-myb. It is expressed in resting T lymphocytes and its levels gradually decrease after mitogenic stimulation to become undetectable at 48 hours. It is also expressed in a subpopulation of large B lymphocytes but not in in vitro activated B cells. Neither of the three members of the myb family of genes was expressed in monocytes and granulocytes, even after functional activation of these cells. Taken together, these data bring further evidence for the role of c-myb in cellular proliferation and on the basis of the kinetics of its induction relative to thymidine uptake, we hypothesize that it may have a role during G1 progression in addition to that already documented for entry into S phase. Furthermore, our studies indicate that another member of the myb family of genes, B-myb, may also be involved in cellular proliferation, because its expression correlates with the induction of mitogenesis.

B-Lymphocytes↗
PubMed1991

Renal and hemodynamic effects of atrial natriuretic peptide infusion are not mediated by peripheral dopaminergic mechanisms.

The possible involvement of peripheral dopaminergic mechanisms in the action of atrial natriuretic peptides was investigated in 10 subjects by administering 200 micrograms h-ANP 99-126 intravenously for 30 min during treatment with 50 mg carbidopa, a peripheral inhibitor of dopamine synthesis, every 8 h, or during placebo. Atrial natriuretic peptide (ANP) infusion during placebo was associated with a significant increase of diuresis, natriuresis, kaliuresis, urinary noradrenaline, and dopamine excretion. Plasma aldosterone significantly decreased. Blood pressure was slightly reduced. The administration of carbidopa significantly reduced urinary dopamine excretion but did not modify natriuresis, diuresis, indexes of adrenergic and renin-aldosterone system activity, blood pressure, or heart rate, both in basal conditions and in response to ANP infusion. We conclude that the effects of exogenous ANP administration are independent from dopaminergic mechanisms that involve the synthesis of dopamine outside the central nervous system, particularly in the kidney.

Adult↗
PubMed1991

Improved left ventricular systolic and diastolic function after regression of cardiac hypertrophy, treatment withdrawal, and redevelopment of hypertension.

The aim of this study was to differentiate the effects of changes of arterial pressure from those of regression of left ventricular hypertrophy (LVH) on systolic and diastolic function at rest and during a rapid increase in afterload, induced by handgrip and cold pressor tests. An additional purpose was to assess the hemodynamic mechanisms responsible for the increase in arterial pressure after treatment withdrawal. Therefore, we evaluated the cardiac anatomy and function (TM echo) at rest and during handgrip and cold pressor tests in 23 hypertensive patients, before therapy and 20-30 days after withdrawal of treatment, which had lasted 6-12 months, when left ventricular mass index (LVMI) was significantly reduced (from 140 +/- 44 to 113 +/- 13 g/m2, p less than 0.001) but the arterial pressure had increased again to pretreatment values (166 +/- 19/105 +/- 7 mm Hg before treatment vs. 162 +/- 15/100 +/- 12 mm Hg). The LVMI reduction was due to a decrease in LV wall thickness, whereas the LV internal dimensions did not change. Systolic function was evaluated by the relationship between LV end-systolic stress (ESS) and fractional shortening (FS): at rest as well as at the peak of handgrip and cold pressor tests, highly significant negative correlations between ESS and FS (range of -0.71 to -0.96) were found. Considering each point of relation between ESS and FS in hypertensive patients, in comparison with 95% prediction limits of the correlation obtained in normal subjects, a "supernormal" systolic function at rest was observed in 10 of 23 patients and a reduced systolic function was not present after treatment withdrawal and redevelopment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Regulation of platelet alpha2 adrenergic receptors in a population of patients with essential arterial hypertension and in normotensive subjects].

The development of specific binding techniques for the study of adrenergic receptors on circulating human blood cells has allowed a better understanding of the physiological alterations of adrenergic receptors and changes of adrenergic receptors in pathological conditions such as hypertension. Alpha adrenoceptors play an important part in blood pressure regulation at several sites. There are contradictory and conflicting reports on whether alpha receptor mechanisms are altered in essential hypertension. To address further the role of alpha 2 adrenoceptors in human essential hypertension the number and the affinity of alpha 2 adrenergic receptors and plasma catecholamine levels were measured in 20 normotensive and 24 hypertensive subjects. The median number of receptors (Bmax) was 159.10 +/- 14.38 fmol/mg protein for controls versus 179.09 +/- 13.26 fmol/mg protein for hypertensives. The median dissociation constant (KD) of the receptors for 3H-Yohimbine was 1.43 +/- 0.17 nmol/l for controls and 1.85 +/- 0.19 nmol/l for hypertensives patients. There were no differences in catecholamine plasma levels between the two groups. In controls platelet alpha 2 receptor number correlated with age (p less than 0.003) but not with blood pressure values. Our results show that measurement of platelet alpha 2 receptor levels and affinity is unable to differentiate a group of hypertensives from normotensives. Nevertheless, we cannot exclude a possible role of peripheral alpha 2 adrenergic receptors in the pathogenesis of high blood pressure.

Adult↗
PubMed1991

Regression of cardiovascular structural changes after long-term antihypertensive treatment with the calcium antagonist nitrendipine.

Regression of cardiovascular structural changes is a main goal of antihypertensive treatment. Nitrendipine is a calcium antagonist of the dihydropiridine group that may be given once daily. In different animal models of experimental hypertension, nitrendipine was shown to reduce blood pressure (BP) and left ventricular (LV) mass, to prevent early mortality, and to limit the development of vascular lesions. It has also been proposed that nitrendipine is able to preserve tissue integrity and increase life span in malignant hypertension, because it prevents a deleterious calcium overload in the heart and arterial vessels. In humans, the effect of nitrendipine on LV mass has been evaluated in a limited number of studies with conflicting results. It has been shown that nitrendipine is able to increase the compliance of large arteries; its effect on vascular structural changes has never been reported. In this study, nitrendipine (20 mg o.d.) was given to 10 hypertensive patients. BP, (ambulatory BP monitoring) heart rate (HR), LV mass and function (TM echo, 2D guided), forearm minimal vascular resistance (min VR = BP/max blood flow--venous occlusion plethysmography--taken as an index of vascular STC), plasma renin activity (PRA), plasma catecholamines (NE and E), and aldosterone (ALD) were measured during placebo, after 2 and 6 months of treatment. BP was significantly reduced and HR was slightly increased. After 6 months of treatment a significant reduction of LV mass index (p less than 0.001) and of min VR (p less than 0.002) was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL).

A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens.

Adolescent↗
PubMed1990

Expression of multiple alpha 2-adrenergic receptor messenger RNA species in rat tissues.

We used a human platelet alpha 2-adrenergic receptor probe to study the tissue distribution and messenger RNA (mRNA) forms of the rat alpha 2-adrenergic receptor. Under stringent conditions of hybridization and washing, we detected an mRNA species of 3.8 kb. The abundance of this form follows the order spleen, kidney, brain stem and cortex, and skeletal muscle and lung and is consistent with the reported abundance and tissue distribution of the alpha 2 receptor activity. A 3.0 kb mRNA form was also detected in cerebral cortex and brain stem and a 4.1 kb mRNA form was observed in kidney under less stringent hybridization conditions. The tissue distribution of the 3.0 kb form is different from that of alpha 1- and beta-adrenergic receptors and the D2 dopaminergic receptor. The mRNA analysis combined with Southern blot analysis of rat and human genomic DNA indicate that: 1) in addition to a 3.8 kb rat alpha 2-adrenergic receptor transcript, there are other mRNA forms in the rat that do not correspond to previously described adrenergic receptor mRNA species and 2) more than one alpha 2-adrenergic receptor gene in the rat is expressed in a tissue-specific manner.

Animals↗
PubMed1990

Effect of chronic ursocholic acid administration on bile lipid composition and bile acid pool size in gallstone patients.

We assessed the effect of chronic (4-6 weeks) administration of ursocholic acid (UCA) (15 mg/kg/day), a natural bile acid with poor detergent capacity, on biliary lipid composition of gallbladder bile (n = 26) and bile acid pool size (n = 5) in gallstone patients. During treatment the biliary molar percentage UCA increased from trace values to 28% (p less than 0.001). This effect was accompanied by an increase in molar percentage deoxycholic acid from 16% to 33% (p less than 0.001). Total bile acid pool size remained unchanged during UCA administration; cholic acid and chenodeoxycholic acid pool sizes decreased from 1.0 to 0.6 mmol (p less than 0.05) and from 1.6 to 0.9 mmol (p less than 0.05), respectively. The molar percentage cholesterol of gallbladder bile decreased from 9.8% to 7.0% (p less than 0.001) during UCA, but bile remained supersaturated with cholesterol in 21 patients. The weak effect on biliary lipid composition and the increase of potentially toxic deoxycholic acid in bile suggest that UCA is unlikely to replace ursodeoxycholic and chenodeoxycholic acid for medical treatment of gallstones.

Adult↗
PubMed1990

[Activity and number of lymphocyte beta adrenergic receptors after protracted treatment with mepindolol sulfate of patients with essential arterial hypertension].

beta-Blockers are widely used in the treatment of high blood pressure. To study clinical and pharmacological role of beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA), lymphocyte beta 2-adrenoceptor density, assessed by 3H-dihydroalprenolol binding, was investigated in 10 hypertensive patients (8 male, 2 female) aged 20-62 years before and after treatment with mepindolol (5 mg o.i.d.). After 3 months of therapy, both systolic (from 169.7 +/- 28.3 mmHg to 146.5 +/- 17.6 mmHg) and diastolic (from 108.7 +/- 17.5 mmHg to 93.6 +/- 8.7 mmHg) blood pressure decreased significantly. Similarly heart rate decreased after treatment (from 76.5 +/- 10.1 b/min to 62.7 +/- 3.4 b/min). Mepindolol treatment decreased beta 2-adrenoceptor density from 1112.2 +/- 459.6 sites/cell to 295.1 +/- 131.2 sites/cell. Plasma noradrenaline values did not correlate with lymphocyte beta 2-receptor number both before and after treatment. Our results show that ISA may play an important role in modulating beta 2-adrenoceptor density on lymphocyte surface. This biological effect could be relevant in reducing the so called "propranolol rebound effect".

Adult↗
PubMed1990

[Increase by ANP and ADH of the duration of activation and deactivation of the cardiopulmonary baroreceptor reflex: modification in the presence of left ventricular hypertrophy].

The involvement of cardiopulmonary and arterial sinoaortic receptors in the control of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) release is still controversial in humans. Moreover, it is not clear if this control may be impaired in hypertensive patients with left ventricular hypertrophy (LVH). We studied 17 male subjects, age 18-58 (6 normotensives and 9 mild hypertensives, 5 without and 4 with LVH). Each subject underwent selective loading and unloading of cardiopulmonary receptors, in a randomized sequence, by application of a positive (LBPP) or negative (LENP) pressure to the lower body (steps: +10, +20, +40, -10, -40 mmHg, each for about 30 min), through a plexyglass-constructed tubular apparatus with a rubber adhesion round the patients' waist. Blood samples were taken at the end of every step for measurement of ADH, ANP, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. Cuff arterial pressure was measured every 5 min, while heart rate was evaluated by continuous ECG recording. Hypertensive subjects underwent right atrial pressure measurement by an iv catheter and forearm blood flow evaluation at rest and during the different steps (venous occlusion plethysmography). During LBNP, ADH plasma levels increased progressively, but the increase became statistically significant only at the step of -40 mmHg. ANP increased significantly during LBPP. Taking into account only hypertensive patients, a consistent reduction in the changes of ADH and ANP plasma levels, respectively during LBNP and LBPP in patients with LVH in respect to those without LVH was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Plasma norepinephrine and heart rate dynamics during recovery from submaximal exercise in man.

The time course of heart rate (HR) and venous blood norepinephrine concentration [NE], as an expression of the sympathetic nervous activity (SNA), was studied in six sedentary young men during recovery from three periods of cycle ergometer exercise at 21% +/- 2.8%, 43% +/- 2.1% and 65% +/- 2.3% of VO2max respectively (mean +/- SE). The HR decreased mono-exponentially with tau values of 13.6 +/- 1.6 s, 32.7 +/- 5.6 s and 55.8 +/- 8.1 s respectively in the three periods of exercise. At the low exercise level no change in [NE] was found. At medium and high exercise intensity: (a) [NE] increased significantly at the 5th min of exercise (delta [NE] = 207.7 +/- 22.5 pg.ml-1 and 521.3 +/- 58.3 pg.ml-1 respectively); (b) after a time lag of 1 min [NE] decreased exponentially (tau = 87 s and 101 s respectively); (c) in the 1st min HR decreased about 35 beats.min-1; (d) from the 2nd to 5th min of recovery HR and [NE] were linearly related (100 pg.ml-1 delta [NE] congruent to 5 beats.min-1). In the 1st min of recovery, independent of the exercise intensity, the adjustment of HR appears to have been due mainly to the prompt restoration of vagal tone. The further decrease in HR toward the resting value could then be attributed to the return of SNA to the pre-exercise level.

Adult↗
PubMed1989

Quantitative measurement of biliary excretion and of gall bladder concentration of drugs under physiological conditions in man.

Gall bladder storage of hepatic bile prevents complete recovery of biliary excretion of drugs to be obtained under physiological conditions in man. The aim of this study was to develop and validate a method for simultaneous measurement of gall bladder storage of a cholephilic drug, and of its duodenal excretion and t1/2 in bile. Duodenal perfusion using polyethylene glycol as intestinal recovery marker for measurement of drug duodenal excretion, with an iv bolus of 99mTc HIDA for measurement of drug mass within the gall bladder was used. Gall bladder volume was measured by ultrasonography. T1/2 in bile was measured by relating drug duodenal excretion to that of bile acid used as an endogenous bile marker. The use of bile acid as biliary marker was validated in two subjects receiving simultaneous iv infusion of indocyanine green. Seven healthy subjects were studied using a beta-lattam antibiotic, Cefotetan 1 g iv, as test drug. Median values during the study period (seven hours) were 51.1 mg for Cefotetan duodenal excretion, 45.2 mg for gall bladder mass and 2.8 mg/ml for concentration within the gall bladder. T1/2 of the drug in bile was 100 minutes. This technique enables measurement of mass and concentration of drugs within the gall bladder to be carried out, in addition to measurements of t1/2 of drugs in bile. These measurements may have specific application for assessment of potential efficacy of antibiotics in biliary tract infections, as well as general application for assessment of biliary excretory kinetics of drugs.

Adult↗