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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 19 recordsLinked to original sources
PubMed1992

Functional and metabolic effects of propionyl-L-carnitine in the isolated perfused hypertrophied rat heart.

Aim of this study was to assess the effect of propionyl-L-carnitine (PLC), a naturally occurring derivative of L-carnitine, in cardiac hypertrophy induced by pressure overload in rats. The abdominal aorta was banded and the rats received one daily administration of PLC (50 mg/kg) or saline for four days. The hearts were excised 24 h after the last administration and were perfused retrogradely with oxygenated Krebs-Henseleit buffer containing 1.2 mM palmitate bound to 3% (w/v) albumin, 2.5 microM PLC and 25 microM L-carnitine. A saline-filled balloon was inserted into the left ventricle and the heart contractility was measured at three volumes of the balloon, corresponding to zero diastolic pressure and to increased volumes (110 and 220 microliters) over the zero volume. At the end of the perfusion, the hearts were freeze-clamped, weighed and analyzed for adenine nucleotide and phosphocreatine (PCr) content by HPLC methods. No differences in the myocardial performance were found at zero diastolic pressure. In contrast, at high intraventricular volume, the maximal rate of ventricular relaxation was increased in PLC-treated with respect to saline-treated controls (p < 0.05). In addition, the increase of the end-diastolic pressure at increasing balloon volume was more marked in controls than in the PLC-treated hearts (p < 0.02). These data correlate well with the measured higher level of total adenine nucleotides (p < 0.05) and ATP (p < 0.02) in the PLC-treated hearts, while PCr was the same in both groups. Parallel experiments performed in the absence of palmitate in the perfusing media failed to show any effect of PLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Na+/K+/Cl- cotransport in resealed ghosts from erythrocytes of the Milan hypertensive rats.

The erythrocytes (RBC) of the Milan hypertensive rats (MHS) have a smaller volume and faster Na+/K+/Cl- cotransport than RBC from normotensive controls (MNS). The difference in Na+/K+/Cl- cotransport is no longer present in inside-out Vesicles (IOV) of RBC membrane. To differentiate between cytoplasmic or membrane skeleton abnormalities as possible causes of these differences. Resealed ghosts (RG) were used to measure ion transport systems. The following results have been obtained: (1) RG from MHS have a smaller volume than MNS (mean +/- S.E. 20.7 +/- 0.45 vs. 22.09 +/- 0.42 fl, P < 0.05). (2) RG showed a bumetanide-sensitive Na efflux that retains the characteristics of the Na+/K+/Cl- cotransport of the original RBC: it is K(+)- and Cl(-)-sensitive and dependent on the intracellular Na+ concentration. (3) The Na+/K+/Cl- cotransport was faster in RG from MHS than in those from MNS (mean +/- S.E. 0.095 +/- 0.01 vs. 0.066 +/- 0.01 rate constant h-1, P < 0.01). These results, together with those of IOV, support the hypothesis that an abnormality in the membrane skeletal proteins may play a role in the different Na+/K+/Cl- cotransport modulation between MHS and MNS erythrocytes.

Animals↗
PubMed1992

Effect of amiloride analogues on sodium transport in renal brush border membrane vesicles from Milan hypertensive rats.

The effect of ethylisopropyl-amiloride (EIPA) and phenamil on sodium uptake in renal brush border membrane vesicles from prehypertensive rats of the Milan strain (MHS) and their normotensive controls (MNS) was investigated. In the presence of both a membrane potential and a pH gradient a differential effect of EIPA and phenamil was evidenced between the two rat strains. In the absence of a pH gradient, but in the presence of a membrane potential, EIPA was about two-fold more potent than phenamil in inhibiting sodium transport in both rat strains, excluding the presence of epithelial sodium channels in our BBMV preparations. Taken together these results support the hypothesis that a structurally different Na+/H+ exchanger located on the brush border membrane may be involved in the increased tubular sodium reabsorption observed in vivo in hypertensive rats.

Amiloride↗
PubMed1992

Defective methionine metabolism in cirrhosis: relation to severity of liver disease.

A block in the transsulfuration pathway has previously been suggested in cirrhosis on the basis of increased fasting methionine concentrations, decreased methionine elimination and low levels of methionine end products. To date, methionine elimination has never been studied under controlled steady-state conditions, and the relation of the severity of liver disease to impaired methionine metabolism has not been clarified. We measured methionine plasma clearance in 6 control subjects and in 12 patients with cirrhosis during steady-state conditions obtained by a primed, continuous methionine infusion. In the presence of high-normal fasting methionine concentrations (range = 14 to 69 mumol.L-1 in controls and 26 to 151 mumol.L-1 in cirrhotic patients), methionine plasma clearance was reduced in cirrhotic patients (2.25 +/- S.D. 0.43 ml.sec-1 vs. 2.86 +/- S.D. 0.43 ml.sec-1 in controls; p less than 0.05), whereas methionine half-life was increased (282 +/- 90 min vs. 187 +/- 25 min in controls; p less than 0.05). Fasting methionine significantly correlated with methionine clearance. The infused methionine was not degraded to urea to any significant extent in cirrhotic patients, whereas a threefold increase in urinary urea nitrogen excretion rate was observed in controls. Similarly, taurine concentrations significantly increased both in plasma and in the urine in controls but not in cirrhotic patients. In cirrhotic patients methionine plasma clearance significantly correlated with galactose elimination capacity (r = 0.818) and with the Child-Pugh score (rs = -0.795). The study supports a major role of impaired liver cell function in the reduced metabolism of methionine and decreased formation of methionine end products that occur in cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A novel insight into the mechanism of the antithrombotic action of defibrotide.

Defibrotide is a polydeoxyribonucleotide sodium salt with antithrombotic properties. These properties have been attributed to its profibrinolytic activity [increase of tissue plasminogen activator (t-PA) activity, concomitant decrease of that of plasminogen activator inhibitor (PAI)], but there could conceivably be other factor(s). To look for these, we studied Defibrotide in a thrombosis model (pulmonary thromboembolism in mice) in which free radicals play a pivotal role. Defibrotide was found to be active after both intravenous and oral administration. Defibrotide behaved in vitro like a scavenger of H2O2 but not of O2.- in cell-free systems. Defibrotide added in vitro to cellular systems decreased the stimulated release of beta-glucuronidase from polymorphonuclear cells (PMNs), the luminol chemiluminescence induced by oxygen species generated by stimulated PMNs and the generation of O2.- from stimulated macrophages. We think that the antithrombotic activity of Defibrotide is based on other factor(s) in addition to profibrinolytic activity, i.e., some scavenger activity and desensitization of cells involved in thrombus formation must also be taken into account.

Animals↗
PubMed1992

Diagnostic and therapeutic problems in multicentric renal angiomyolipoma.

Multicentric renal angiomyolipoma is a rare form of benign tumor. However, its effective incidence as evaluated in autopsy studies may be as high as 8%. There are 2 main types of renal angiomyolipoma, that is isolated forms and those associated with other diseases, such as phakomatosis, polycystic kidneys and fibromuscular dysplasia. The tumor may also display malignant behavior with local invasiveness and regional lymph node involvement. However, the clinical course is benign and multicentricity is important for prognosis. Histopathological diagnosis often is difficult. Immunohistochemical analysis of surgical specimens using a panel of monoclonal antibodies, including HMB-45 and actin, enabled us to make a definitive diagnosis in 3 cases of multicentric renal angiomyolipoma.

Adolescent↗
PubMed1992

Polyamine plasma levels and liver regeneration following partial hepatic resection in man.

Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means of a sensitive HPLC technique, the fasting plasma concentrations of polyamines were measured serially in 11 patients who underwent partial hepatic resection because of focal liver lesions. Samples were obtained before surgery and over the next 6 months, during hepatic regeneration. Liver volume was also measured by ultrasound on the basis of the 3 maximum diameters of the liver. From 2 to 4 weeks after surgery, plasma putrescine increased by a maximum of 78%, and spermidine by approximately 50%. No changes were observed in spermine levels. The spermidine/spermine ratio nearly doubled during liver regeneration. The volume of the liver decrease from 1505 [SD 236] ml to 743 [151] ml after resection, and returned to nearly normal values after 6 months (1231 [100] ml, p < 0.05 vs. basal values). The liver regeneration rate was highest 2-4 weeks after resection, and declined thereafter, when prevailing polyamine concentrations returned to normal. These data show that liver regeneration is accompanied by a significant increase in fasting putrescine and spermidine concentrations, which might be biochemical signals of active liver cell regeneration.

Adult↗
PubMed1992

Differences in ouabain-induced natriuresis between isolated kidneys of Milan hypertensive and normotensive rats.

1. Several observations support the hypothesis that in rats of the Milan hypertensive strain elevated levels of a circulating ouabain-like factor might normalize the elevated Na+ reabsorption, but, on the other hand, might contribute to the development of hypertension. 2. As the receptor occupancy of this endogenous factor seems to be reversible, the aim of our study was to test, in vitro, the hypothesis of its presence in isolated kidneys from Milan hypertensive rats by studying the response to exogenous ouabain before and after prolonged washing. 3. The kidneys were isolated from adult Milan hypertensive rats and from age-matched normotensive controls and ouabain was given at two different experimental time intervals: shortly (15 min) after washout or after a further 60 min of washout (75 min in total). Comparative experiments with the diuretic hydrochlorothiazide were performed using the same protocol. 4. Ouabain given after 15 min of perfusion caused an increase in renal vascular resistance, diuresis and natriuresis; these haemodynamic and tubular responses were similar in kidneys from both Milan hypertensive and Milan normotensive rats. If given after the washout period, ouabain caused a comparable increase in renal vascular resistance, but a significantly greater natriuresis in kidneys from Milan hypertensive rats as compared with kidneys from Milan normotensive rats. On the other hand, hydrochlorothiazide caused similar natriuresis in kidneys from both strains after washout. 5. These results support the hypothesis that a factor, capable of interacting with the ouabain receptor on the Na+/K(+)-ATPase of tubular cells, is present in the kidney of adult Milan hypertensive rats and that it can be removed by prolonged washout.

Animals↗
PubMed1992

Ouabainlike factor in Milan hypertensive rats.

Ouabainlike factor (OLF) has been extracted from the hypothalamus and adrenals of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability to 1) inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, 2) displace [3H]ouabain binding, and 3) inhibit purified dog kidney Na-K-adenosinetriphosphatase (ATPase). Rat and bovine OLF have similar characteristics. Those that are close to ouabain are 1) ligand conditions for maximal inhibitory activity, 2) high-performance liquid chromatography retention time, 3) reversibility of inhibitory activity on Na-K-ATPase, 4) reduced Na-K pump inhibitory activity by K, 5) high affinity for Na-K-ATPase, and 6) no activity on calcium ATPase. OLF does not resemble ouabain in the following characteristics: 1) the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain and 2) the capacity of OLF to inhibit renal Na-K-ATPase isoforms is greater when the enzyme is obtained from adult rather than young rats. The yield of OLF is greater from MHS than MNS. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.

Adrenal Glands↗
PubMed1992

Left atrial size in paroxysmal atrial fibrillation: echocardiographic evaluation and follow-up.

Echocardiographic measurement of left atrial size was performed in 24 patients (13 males, 11 females, median age 56 years) with idiopathic paroxysmal atrial fibrillation (IPAF). A second measurement was done, after a mean period of 20 months. Our study showed that: (1) the patients with IPAF had normal-sized atria, the dimensions of which remained unmodified over a 20-month period; and (2) no correlation was found between the frequency of recurrent arrhythmic episodes and left atrial size. Since atrial enlargement, which is the known risk factor for embolic stroke, was not observed in our patients, we conclude that patients with IPAF do not need anticoagulant therapy.

Adult↗
PubMed1992

A clinical double-blind study of flumazenil, antagonist of benzodiazepines, in loco-regional anesthesia.

Flumazenil has been studied for antagonism of the residual sedative effect of midazolam administered as a complement of loco-regional anesthesias. Highly significant differences appeared between the patients receiving placebos and those receiving flumazenil, showing a quick suppression of the lasting sedative effects of midazolam. At the dosage of 1 mg, flumazenil seemed to have a more efficient and complete effect than the 0.5 mg dosage. Tolerance to flumazenil was excellent with the exception of one case of agitation and disorientation, in a patient chronic consumer of benzodiazepines thus this could be considered as a deprivation syndrome. In conclusion, flumazenil should certainly have a place in the pharmacological stores of the anesthesiologist.

Aged↗
PubMed1992

Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy.

Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats. Separate groups of rats were used for (a) determination of myocardial carnitine content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of performance and metabolic state of Langendorff perfused hearts. Results showed the following: (i) The myocardial carnitine content was inversely correlated to cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a. for 4 days) restored it to normal values (ii) The PLC effect on cardiac function was significantly and directly related to cardiac hypertrophy [correlations between heart weight and percent changes in cardiovascular parameters: cardiac output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral resistance (TPR) was significantly different from that of saline (CO, CW, SV, and SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h after the first PLC administration and significantly diminished following a 4 day suspension of the treatment. (iii) Perfused hearts from PLC-treated rats displayed a significantly lower left ventricular end-diastolic pressure (p less than 0.01) and greater relaxation rate (p less than 0.05) than those from control rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP, and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP, p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show that PLC exerts a stimulatory activity on hearts with hypertrophy and low carnitine content, implying that carnitine deficiency may contribute to the depression of cardiac function in this model.

Adenine Nucleotides↗
PubMed1992

[Lipoprotein (a), a new atherosclerotic risk factor. Blood levels in normal pregnancy].

Serum levels of lipoprotein (a), an important factor of atherosclerotic risk, in 32 patients during normal pregnancy and puerperium, were evaluated. Our results show a significant increase of the level of this lipoprotein (M = 20 mg/dl) versus controls (M = 16 mg/dl) during all periods of pregnancy, with a very significant increase at week 20th.

Arteriosclerosis↗
PubMed1992

Anthropometric assessment of the nutritional status of patients with liver cirrhosis in an Italian population.

A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known. Anthropometric measurements were carried out in 200 patients with cirrhosis (135 M, 65 F). Liver disease was related to alcohol abuse in 77 cases, but most patients had stopped alcohol for at least 6 months before study. In comparison to a normal elderly Italian and to an age-matched North-American population, 5 to 45% of male patients with cirrhosis and 10 to 30% of females had signs of malnutrition, the proportion being variable according to the test used. Male patients showed a remarkable reduction in muscle mass (30-45% of patients, mainly in the presence of moderate-to-severe or severe liver failure), whereas female patients showed a more remarkable reduction of fat stores (15-30% of cases), with advancing liver failure, and a less severe reduction in muscle mass. No direct effect of alcohol was demonstrated in this selected population.

Adipose Tissue↗