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Biomedical subjects

G Bruschi

Publications and source records attributed to G Bruschi.

At least 37 records · Page 2Linked to original sources
PubMed1988

Increased sensitivity to protein kinase C activation in aortas of spontaneously hypertensive rats.

The aortic muscle of spontaneously hypertensive (SHR) and normotensive control (WKY) rats was stimulated with phorbol esters and the contractile response was measured as isometric tension. Phorbol esters are known activators of protein kinase C. The aortas of SHR were characterized by the following distinct alterations in the response to phorbol myristate acetate: (1) increased sensitivity: half-maximal force was achieved at 62 +/- 6 nmol/l phorbol myristate acetate in SHR and 105 +/- 8 nmol/l in WKY; (2) increased contractility: the maximal force developed by phorbol myristate acetate was greater in SHR aortas (1.9 +/- 0.3 versus 1.6 +/- 0.2 g in WKY) compared with the decreased contractility generated with noradrenaline and high levels of potassium; (3) decreased dependency on extracellular calcium for half-maximal tension: in the presence of 3 mumol/l phorbol myristate acetate 50% of maximal force was attained at 21 +/- 8 mumol/l extracellular calcium compared with 49 +/- 9 mumol/l in WKY; (4) diminished relaxation in response to excess extracellular calcium: phorbol myristate acetate-precontracted WKY aortas began to relax when calcium was raised above 4 mmol/l in the bath and relaxation reached 51% at 8-10 mmol/l. Relaxation was almost absent in SHR (3-7%). Hence, there is an abnormality in the response to protein kinase C activation by phorbol esters in SHR vascular smooth muscle. Intracellular calcium appears to be involved. Studies of protein kinase C will prove important in understanding vascular smooth muscle function in normal and abnormal states.

Animals↗
PubMed1988

The vasodilator effect of human atrial natriuretic factor (99-126) on human omental arteries.

The effect of synthetic human atrial natriuretic factor [ANF-(99-126)] on human omental arteries was investigated. The compound produced concentration-dependent relaxation, 10, 50 and 90% of maximum effect being observed at about 1, 10 and 100 nmol/l, respectively. These concentrations are considerably higher than those measured by radio-immunoassay in human plasma, even under extreme conditions (0.001-0.3 nmol/l). Therefore, ANF can dilate human resistance-size arteries, but whether it does so under physiological conditions has not been established.

Adult↗
PubMed1988

Myoplasmic Ca2+-force relationship studied with fura-2 during stimulation of rat aortic smooth muscle.

The intracellular Ca indicator fura-2 was used for simultaneous measurements of intracellular free Ca (Ca2+i) and force in arterial smooth muscle. Rat aortic medial rings were submitted to fluorometry in a geometrical arrangement resembling that of adherent cell layers. A rigid force-transducing system served to immobilize the tissue and record the developed force quasi-isometrically. Stimulation was performed with norepinephrine (NE), KCl depolarization (high K), and a nonfluorescent Ca ionophore (ionomycin) at varying extracellular Ca concentrations. The following facts were observed. NE, high K, and ionomycin increased tension along with fura-2-reported Ca2+i; under any circumstances tension was Ca2+i dependent and could be varied by manipulating Ca2+i. However, NE and high K determined a parallel increase in the effectiveness of Ca2+i in comparison with the simple ionophore, i.e., they increased the force-to-Ca2+i ratio. NE and high K produced half-maximal tension at fura-2 estimated Ca2+i of 0.10 and 0.13 microM, whereas ionomycin required 0.6 microM to achieve the same amount of force. It is inferred that Ca2+i is a determinant of vascular contraction, but some results suggest the existence of factors that sensitize the contractile machinery to Ca.

Animals↗
PubMed1988

Dietary sodium change in primary aldosteronism. Atrial natriuretic factor, hormonal, and vascular responses.

Atrial natriuretic factor (ANF) may be physiopathologically involved in several clinical conditions including human hypertension. However, few data are available regarding this putative hormone and its relationship to aldosterone, blood pressure, and vascular responsiveness to alpha-adrenergic receptor stimulation in primary aldosteronism, a volume-expanded, low-renin model of human hypertension. For this reason, the behavior of supine and upright plasma ANF as related to aldosterone, blood pressure, and forearm alpha-adrenergic sensitivity (plethysmographic technique) to intra-arterial norepinephrine infusion was studied in eight patients with primary aldosteronism (five with adenomas, three with hyperplasia) before and at the end of two sequential 1-week low (20 mmol/day) and high sodium (200 mmol/day) diet periods. Basal, predict ANF concentrations decreased and increased after low and high sodium intakes, respectively. Furthermore, highly significant postural ANF decrements after 1 hour of standing occurred with each diet, although they were lower after the low than after the high sodium diet. Plasma aldosterone, either supine or upright, was insensitive to dietary sodium manipulations, suggesting the absence of ANF-mediated control of aldosterone secretion in our patients. In spite of about twofold higher ANF concentrations during the high than during the low sodium diet, forearm vascular sensitivity to intra-arterial norepinephrine infusion did not change during the study. Furthermore, systemic arterial blood pressure rose to a highly significant extent after dietary sodium content was increased, thus casting doubt on a role for ANF as an endogenous long-term modulator of systemic blood pressure and peripheral alpha-adrenergic sensitivity in patients with primary aldosteronism.

Adult↗
PubMed1988

Cisplatin and etoposide as second-line chemotherapy in patients with small cell lung cancer.

Twenty-seven evaluable patients with small cell lung cancer (SCLC) resistant to, or relapsed after induction combination chemotherapy (CT) were treated with etoposide (VP16) plus cisplatin (DDP). Previous treatment was: alternating CT with cyclophosphamide (C), adriamycin (A), methotrexate (M), procarbazine (P) (CAMP)/VP16, BCNU (B), hexamethylmelamine (H) (VP16 BH) in 16 patients; C, A, vincristine (CAV) in 6 patients; C, A, and VP16 (CAVP16) in 5 patients. We observed 2 (7%) complete responses (CR) and 9 (33%) partial responses (PR). Duration of CRs was 8 and 14 weeks, respectively. PRs lasted a median of 22 weeks (range 16-44). Seven of 21 (33%) patients previously treated with VP16 responded to DDP plus VP16 (D-V). These results confirm D-V regimen as active in SCLC patients even when heavily pretreated. Our 33% response in patients who had VP16 in their induction treatment regimen provides further evidence of an important potentiating effect of DDP, as reported in animal system.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Preoperative embolization of angiomas of the face. Remote angiographic results].

Preoperative embolization was performed on 27 patients with facial angiomas supplied by the external carotid branches. Sixteen were males and 11 females; 13 of these angiomas were high-flow arteriovenous (A-V), 14 were low-flow capillary malformations. Fourteen patients underwent surgical removal after preoperative embolization; in this group embolization was carried out with Spongel in 3 cases and with Lyodura in 11 cases. In 12 of these patients the last angiographic examination was performed 3-6 years later: angiography evidenced no recurrence in 8 cases (67%), while in 3 cases (25%) there was capillary residual angioma of negligible size. Treatment was unsuccessful in one patient only, due to the large recurrent A-V angioma. Thirteen patients underwent embolization only, which was carried out with Lyodura in 10 cases, and with Ivalon in 3 cases. On 12 of these patients the last angiographic study was performed 2-14 months later: there was recurrent A-V angioma in 5 patients (42%), who underwent a subsequent embolization; angiography evidenced no recurrence in the other 7 patients (58%). In both series, the best results were obtained in the patients with low-flow capillary angiomas. Embolization and subsequent surgical removal are the treatment of choice for facial angiomas; embolization alone is useful in the management of surgically inaccessible vascular malformations, and it can be the only treatment in patients with small low-flow angiomas when distal occlusion of the feeding vessels with Lyodura or Ivalon particles is performed.

Adolescent↗
PubMed1987

Physiological stimuli to atrial natriuretic peptide secretion in normal humans.

We tested the response of plasma atrial natriuretic peptide (ANP) levels to the following physiological stimuli: postural changes; head-out water immersion; and physical exercise. Plasma ANP (p-ANP) levels were assessed by a specific, sensitive radio-immunoassay. Plasma ANP rose significantly when posture shifted from upright to recumbent for 1 h, but fell again to basal values after 10 min standing. Circadian variations did not affect the posture study. Head-out water immersion produced a prompt and remarkable (sevenfold) increase in p-ANP, with a plateau reached after 1 h and held until the end of the experiment (2 h). Plasma ANP levels were measured in 10 normal subjects performing supine treadmill exercise at 50% of maximum aerobic capacity for 30 min. Plasma ANP rose from baseline supine values after 15 min exercise, and remained elevated during the following 15 min exercise. During the recovery phase ANP showed a trend towards baseline values, with a 38% decrease attained after 30 min. We propose that the above tests could be used as ANP-stimulating manoeuvres in physiological and clinical conditions in man.

Adult↗
PubMed1987

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Adrenal Glands↗
PubMed1986

The mechanism of Ca2+i increase in blood cells of spontaneously hypertensive rats.

Cytoplasmic free calcium (Ca2+i) is increased in platelets and lymphocytes of spontaneously hypertensive rats (SHR) and, to a lesser extent, in essential hypertensive patients. In this study, a method was devised to evaluate cellular Ca fluxes and the cellular Ca buffering power by means of the intracellular Ca indicator Quin-2. Ca influx was measured under conditions of Ca-pump inhibition, either by vanadate or ATP depletion. Lymphocytes of 5-month-old SHR were compared with those of normotensive Wistar-Kyoto rats (WKY). In both strains, the Ca entry rate and the cellular buffering capacity were higher in vanadate-treated than in ATP-depleted cells. SH rats exhibited a higher Ca influx and a greater intracellular Ca buffering power when vanadate was used to stop the Ca pump; these differences, however, were abolished in ATP-depleted lymphocytes. It is suggested that Ca entry in lymphocytes is ATP-dependent. Accelerated Ca entry in SHR can account for the previously reported higher levels of intracellular free Ca.

Adenosine Triphosphate↗
PubMed1986

Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.

Animals↗
PubMed1986

Interaction of beta-adrenergic antagonists with local anaesthetic acceptor sites.

H3-dihydroalprenolol (H3-DHA) binding in isolated smooth muscle cells has been studied. Two different binding sites have been detected: a high affinity (highly specific) and a low affinity (nonspecific) binding site. Local anaesthetics are able to displace H3-DHA from nonspecific sites with a rank order of potency that mirrors their local anaesthetic activity. This finding correlates, at the molecular level, with the local anaesthetic properties of beta-blockers, as concluded from classical pharmacological experiments.

Adrenergic beta-Antagonists↗
PubMed1985

Cytoplasmic free [Ca2+] is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients.

The cytoplasmic free calcium concentration [( Ca2+]i) was assessed with the fluorescent dye Quin 2 in platelets and lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), essential hypertensive patients (EHP) and normotensive human control subjects (NCS). [Ca2+]i was significantly higher in the platelets of 8- and 20-week-old SHR in comparison with WKY. However, no difference was evident after weaning. Changes of cellular calcium in hypertensive rats apparently evolved simultaneously with the development of high arterial pressure. [Ca2+]i was significantly higher in platelets of EHP than in NCS. In lymphocytes of SHR, [Ca2+]i was not different from WKY at 4 and 8 weeks, but was increased at 14 weeks and at older ages. In EHP, intralymphocytic [Ca2+] was only modestly higher than in controls. On the whole, the results suggest that control of cytoplasmic calcium in these blood cells is similarly affected in human and animal models of primary hypertension.

Adult↗
PubMed1985

Why is [Ca2+]i increased in blood cells in primary hypertension?

In order to explore a previously observed association between raised blood cell cytosolic calcium [Ca2+]i and primary hypertension, resting levels of [Ca2+]i in the Milan hypertensive rat strain (MHS) were measured. The [Ca2+]i was increased significantly at 7 weeks in MHS (116 +/- 8 versus 93 +/- 6 mumol/l, P < 0.005, n = 7) and non-significantly at 5 weeks (109 +/- 7 versus 85 +/- 9 mumol/l, n = 5). In Okamoto-Aoki spontaneous hypertensive rats (SHR), calcium fluxes were measured with Quin 2 in platelets and lymphocytes. Calcium influx was measured during calcium-pump inhibition either with vanadate or ATP-depletion. Influx was increased in vanadate-treated (but not in ATP-depleted) cells of SHR. This suggests an ATP dependence of calcium influx in blood cells which is more pronounced in SHR. Calcium efflux was determined when the influx was stopped by external EGTA. Calcium efflux was [Ca2+]i-dependent and was moderately increased in SHR. The faster efflux in SHR was due to higher [Ca2+]i. The [Ca2+]i-dependency of calcium efflux was comparable in SHR and Wistar-Kyoto (WKY) rats. These results suggest that a slight but significant rise of cytosolic calcium occurs in blood cells in primary hypertension. In Okamoto-Aoki SHR this rise was due to a higher calcium entry rate.

Aminoquinolines↗
PubMed1984

Intracellular free [Ca2+] in circulating lymphocytes of spontaneously hypertensive rats.

In the light of previous reports suggesting a common abnormality of Ca handling in most tissues of hypertensive humans and rats, we applied a novel technique using the fluorescent probe Quin 2 for measurement of cytosolic free Ca2+ in lymphocytes of spontaneously hypertensive rats (SHR). (Ca2+)i is increased in SHR (122.1 +/- 7.4 nM) versus normotensive Wistar-Kyoto (WKY) control rats (81.1 +/- 6.3 nM) Membrane exchange, as challenged by varying the extracellular Ca concentration over a 10(5)-fold range proved to be relatively unimportant in regulating (Ca2+)i and did not significantly affect the difference between SHR and WKY. Catecholamines and ouabain had no appreciable effect on (Ca2+)i. The mechanisms of increased (Ca2+)i in SHR lymphocytes remain to be fully elucidated.

Animals↗