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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 253 records · Page 14Linked to original sources
PubMed1993

Relationships among alterations in renal membrane sodium transport, renin and aminopeptidase M activities in genetic hypertension.

Rats of the Milan Hypertensive Strain (MHS) may be considered a useful model for understanding the genetic molecular mechanism underlying a primary form of hypertension in at least a subgroup of patients. Many differences between MHS and its normotensive control strain (MNS) were found at the organ, cellular and biochemical level. In the present investigation renal cell membrane proteins (BBMV) were analysed by two-dimensional electrophoresis and a difference between MHS and MNS was shown in a polypeptide of 32 kDa, subsequently identified as the C-terminal fragment of aminopeptidase M (APM). The activity of the enzyme was higher in MHS. Genetic relationships between this enzyme and the other biochemical cellular abnormalities of MHS, namely sodium transport in BBMV and renin activity in kidney cortex were investigated in MHS, MNS and in two inbred recombinant strains. This analysis showed that faster sodium transport, low kidney levels of renin and hypertension, but not differences in two-dimensional electrophoretic pattern and in aminopeptidase M activity, cosegregated in recombinant strains. These results are consistent with the hypothesis that the faster sodium transport can be considered a primary cellular abnormality responsible for hypertension in MHS and that the aminopeptidase difference is not involved in the cellular abnormalities.

Aminopeptidases↗
PubMed1993

Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist.

The binding of single-stranded polydeoxyribonucleotides to adenosine A1 and A2 receptors was investigated. Defibrotide, a natural substance with established anti-thrombotic and anti-ischaemic effects, displaced [3H]CHA (N6-cyclohexyl-adenosine) and [3H]NECA (5'-N-ethylcarboxamido-adenosine) concentration dependently, completely and competitively. Ki values of 371 +/- 68 and 688 +/- 115 micrograms/ml (mean +/- S.E.M. of 4-5 replications) were computed for adenosine A1 and A2 sites, respectively. Higher and lower molecular weight polydeoxyribonucleotides displayed comparable affinity, whereas a double-stranded polydeoxyribonucleotide and a polyanion with a negative charge comparable to that of defibrotide were inactive. Defibrotide did not affect the total number of binding sites in radioligand saturation experiments. Defibrotide relaxed the K(+)-contracted guinea-pig trachealis muscle (IC50 = 4001 micrograms/ml) about one-third as potently as the CHA-contracted preparation and as potently as the resting preparation. NECA, a mixed adenosine A1/A2 receptor agonist, behaved similarly. The effects were abolished by the adenosine A1/A2 receptor blocker 8-phenyltheophylline, but not by the selective A1 blocker, 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine. These results demonstrate that defibrotide binds to adenosine receptors and triggers pharmacological responses comparable to those of a known agonist.

Adenosine↗
PubMed1993

Genetic models of arterial hypertension--role of tubular ion transport.

The description of pathogenetic mechanisms underlying different genetic models of essential hypertension is a useful way of illustrating the logical sequence needed to dissect a complex phenotypic condition such as hypertension. The abnormalities in renal function observed in spontaneously hypertensive rats of the Okamoto strain and Milan strain will be emphasized. The description may proceed "downward" from alterations that affect the whole body function to cellular and subcellular levels. However, the identification in the Milan strain rats of a point mutation in the gene coding for adducin, a skeletal protein able to modulate transepithelial sodium transport, provides the opportunity to reconstruct, in an "upward" direction, the sequence of events leading from the single point mutation to the final complex phenotype of essential hypertension.

Animals↗
PubMed1993

Thyroid involvement in chronic inflammatory rheumatological disorders.

The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in other rheumatological disease of possible autoimmune aetiology, such as psoriatic arthritis and ankylosing spondylitis. We measured thyroid volume and function as well as the prevalence of anti-microsome and anti-thyroglobulin antibodies in 107 consecutive patients with rheumatoid arthritis, 42 patients with psoriatic arthritis, and 12 male patients with ankylosing spondylitis. Fifty-two normal subjects were used as controls. The average thyroid volume, measured at ultrasounds, was increased in all groups of patients, and the prevalence of thyroid enlargement (A-P diameter > 20 mm) was 2-3 fold higher in rheumatological disorders in comparison to controls. Both, patients with rheumatoid arthritis and psoriatic arthritis had higher-than-normal fT4 levels and an increased prevalence of anti-microsome antibodies. In the rheumatoid arthritis group alterations in thyroid volume and function were present irrespective of disease activity, whereas in psoriatic arthritis thyroid involvement was confined to patients with active disease. Our data are consistent with a significant thyroid involvement in rheumatological disorders, which is not limited to diseases with a definite autoimmune aetiology.

Adult↗
PubMed1993

Genetics of renal damage in primary hypertension.

Little is known of the genetics of glomerular damage in essential hypertension in humans. The prevalence of end-stage renal disease due to primary hypertension varies from 20% to 30% of all cases of renal failure to as low as 0.002%. This depends not only on differences in diagnostic criteria but also on different racial susceptibility to the disease as well as on different genetic backgrounds in different subsets of individuals of the same race. A review of the literature is provided, together with an example of how a point mutation that causes hypertension in Milan hypertensive rats can provide a model to analyze this issue correctly.

Animals↗
PubMed1993

Benzodiazepine receptors and diazepam binding inhibitor: a possible link between stress, anxiety and the immune system.

This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.

Animals↗
PubMed1993

Prognostic significance of portal hemodynamics in patients with compensated cirrhosis.

The prognostic value of portal hemodynamics, measured by pulsed echo-Doppler, was prospectively evaluated, together with clinical, biochemical and endoscopic parameters, in a series of 50 consecutive patients with compensated cirrhosis. After a mean follow-up of 6 years, 25 patients had died, all from complications of liver disease. Among conventional variables, the step-wise Cox model showed that only the Child-Pugh score independently predicted death (chi 2 = 18.66; p < 0.001). When hemodynamic parameters were added to the Child-Pugh score in the same model, portal blood velocity was shown to add prognostic significance (improvement in chi 2 = 14.06; p = 0.0002; Wald test). The present study shows that a portal blood velocity below the lower limit of controls (10 cm/s) characterizes patients with shorter survival, and suggests that this non-invasive parameter should be associated to the Child-Pugh score in the evaluation of patients with cirrhosis.

Adult↗
PubMed1993

Erythrocyte Na+,K+,Cl- cotransport and kidney function in essential hypertension.

OBJECTIVE: To determine whether essential hypertensive patients with high Na+,K+,Cl- cotransport (COT) display alterations of some indices of kidney tubular reabsorption similar to those observed in Milan hypertensive (MHS) rats, which have high COT in both erythrocytes and kidney tubular cells, and hypertension caused by a primary increase of tubular reabsorption. DESIGN: Two sets of experiments were performed. First, renal function in two subgroups of hypertensive patients (one with 'high' and one with 'normal' COT was compared with that in normotensive controls. Secondly, the natriuretic and diuretic effects of a single oral dose of frusemide (25 mg) were analysed in six high- and in six normal- COT hypertensive patients. RESULTS: Compared with normotensives and with normal-COT hypertensives, high-COT hypertensives had lower fractional uric acid excretion and plasma renin activity with similar glomerular filtration rate and urinary sodium and potassium excretion. COT was negatively correlated with fractional uric acid excretion in the essential hypertensive patients but not in the normotensives. The diuretic natriuretic response to frusemide was much higher in high- than in normal-COT hypertensives. CONCLUSION: These results are consistent with the hypothesis that patients with high COT have abnormal renal handling of sodium similar to that observed in MHS rats.

Adult↗
PubMed1993

Characteristics of a ouabain-like factor from Milan hypertensive rats.

Ouabain-like factor (OLF) has been extracted from hypothalamus and adrenal glands of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability (a) to inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, (b) to displace [3H]ouabain binding, and (c) to inhibit purified dog kidney Na-K-ATPase. Rat and bovine OLF have similar characteristics. Those that are close to ouabain are (a) ligand conditions for maximal inhibitory activity, (b) high-performance liquid chromatography retention time, (c) reversibility of inhibitory activity on Na-K-ATPase, (d) reduced Na-K-pump inhibitory activity by K+, (e) high affinity for Na-K-ATPase, and (f) no activity on Ca(2+)-ATPase. OLF does not resemble ouabain because the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain. The yield of OLF is greater from MHS than MNS hypothalamic and adrenal extracts. 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↗
PubMed1993

The effect of defibrotide on thromboembolism in the pulmonary vasculature of mice and rabbits and in the cerebral vasculature of rabbits.

1. Administration of bovine thrombin (100 u kg-1) into the carotid artery of rabbits induces a sustained accumulation of 111 Indium-labelled platelets within the cranial vasculature over the subsequent 3 h. 2. Intracarotid (i.c.) administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.c. thrombin (100 u kg-1) significantly reduces the ability of thrombin to induce cranial thromboembolism in rabbits. 3. Intravenous (i.v.) administration of thrombin (20 u kg-1) in rabbits induces a reversible accumulation of radiolabelled platelets into the thoracic circulation which is significantly reduced by i.v. administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.v. thrombin. In contrast, platelet accumulation in response to adenosine diphosphate (ADP; 20 micrograms kg-1, i.v.) or platelet activating factor (PAF; 50 ng kg-1, i.v.) is not significantly affected by this treatment. 4. Intravenous administration of the nitric oxide (NO)-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1) potentiates platelet accumulation induced by low dose thrombin (10 u kg-1, i.v.) within the pulmonary vasculature of rabbits. The potentiated response is significantly abrogated following pretreatment with defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h, i.v.). 5. Intravenous injection of human thrombin (1250 u kg-1) to mice induces death within the majority of animals which is significantly reduced by pretreatment with defibrotide (150-175 mg kg-1, i.v.). In contrast, death induced by i.v. collagen (1.25 mg kg-1) plus adrenaline (75 microg kg-1) is not significantly affected by defibrotide pretreatment.6. The inhibitory effect of defibrotide in mice is abolished following concomitant treatment with the inhibitor of fribrinolysis, tranexamic acid (100 mg kg-1, i.v.), but is unaffected following treatment with the cyclo-oxygenase inhibitor, aspirin (300 mg kg-1, i.p.).7. The protective effect of defibrotide against thrombin-induced thromboembolism in the mouse is potentiated by recombinant tissue-plasminogen activator (rt-PA; 1 mg kg-1, i.v.) or unfractionated heparin (10 u kg-1, i.v.) administration.8. The results suggest that defibrotide may possess antithrombotic activity on thrombin-induced thromboembolism which, at least in the mouse, may be partially mediated via induction of the fibrinolytic pathway.

Animals↗
PubMed1993

Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats.

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

Administration, Oral↗
PubMed1993

[Study of spondylodiscitis with magnetic resonance. Use of gadolinium-DTPA].

Eighteen patients suffering from spondylodiscitis were examined with MRI and 22 pathologic levels were identified: 1 cervical, 6 thoracic and 15 lumbosacral. As for etiology, 4 cases were tubercular, 3 strepto-staphylococcal, 3 brucellar 1 strepto-bacteroides and 11 of unknown origin. Five patients underwent MR follow-up 4-9 months after the clinical onset. SE T1- and T2-weighed sequences were always performed and 11 patients, with 13 pathologic levels, also underwent SE T1-weighted sequences with i.v. Gd-DTPA administration. No correlation could be made between the signal intensity of the involved vertebral bodies and disks and etiology. On SE T1-weighted sequences 91% of the vertebral bodies were hypointense, whereas the intervertebral disks were hypointense in 55% of cases and isointense in 45%. On SE T2-weighted sequences, the vertebrae appeared hyperintense in 65% of the cases while the disks were hyperintense in 55% and isointense in 41%. After Gd-DTPA injection signal intensity increased in 100% of cases, both at the body and at the disk. In 6 cases an inflammatory infiltration of the intracanalar structures was found, whose identifications was possible, in 4 cases, only after contrast medium injection. In the follow-up of 5 cases at 4-9 months the vertebral bodies remained hypointense in 3 cases on T1-weighted sequences, while in 2 cases signal intensity tended to normalize. Signal normalized in 4 cases on T2-weighted sequences. In 2 follow-up examinations disk structures were never depicted, neither on T1- nor on T2-weighted sequences. To conclude, T1-weighted sequences appear to be more sensitive than T2-weighted sequences to demonstrate inflammatory processes in the vertebral bodies, while the two sequences are equivalent to evaluate the disks. Gadolinium-enhanced T1-weighted sequences were more sensitive than the T1- and T2-weighted ones, especially to assess the extent of inflammatory processes into the spinal canal and to evaluate their persistence. The authors suggest the use of unenhanced and enhanced SE T1-weighted sequences only at least in the follow-up of spondylodiscitis.

Adolescent↗
PubMed1993

Unresponsiveness of hepatic nitrogen metabolism to glucagon infusion in patients with cirrhosis: dependence on liver cell failure.

Glucagon exerts an up-regulatory effect on hepatic nitrogen metabolism in healthy subjects, but its potential role in the presence of liver failure is uncertain. The effects of glucagon on urea synthesis and hepatic nitrogen clearance during alanine infusion were studied in five control subjects and six cirrhotic patients in paired experiments at spontaneous glucagon concentrations and at high physiological glucagon levels (approximately 300 to 500 pmol.L-1) induced by a 7.5-hr continuous glucagon infusion. In all experiments the urea nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentrations. At spontaneous glucagon concentrations the dynamics of alpha-amino nitrogen to urea nitrogen conversion (functional hepatic nitrogen clearance) were significantly reduced in cirrhosis (23.2 +/- 6.7 L.hr-1 vs. 35.3 +/- 8.0 L.hr-1, p < 0.05) in relation to decreased liver function. Glucagon superinfusion caused a 63% increase in the dynamics of the process in controls (57.7 +/- 11.0 L.hr-1; p vs. spontaneous glucagon, p < 0.01), whereas in cirrhosis it increased on average by only 15% (26.7 +/- 10.7; p = NS). The glucagon-induced change in functional hepatic nitrogen clearance significantly correlated with galactose elimination capacity and antipyrine clearance (r = 0.905 and 0.964, respectively). Glucagon, in high physiological concentrations achieved with glucagon infusion, does not produce significant effects on hepatic nitrogen metabolism in cirrhosis. The reduced sensitivity of the cirrhotic liver to glucagon seems to be dependent on decreased hepatocellular function. These data do not support the role of glucagon as a "catabolic" hormone in cirrhosis.

Adult↗
PubMed1993

Topology of two DBI receptors in human lymphocytes.

High-affinity binding sites for the isoquinoline carboxamide PK 11195 and 4'-chlorodiazepam (4'CD) in human lymphocytes are recognized by two putative endogenous ligands: diazepam binding inhibitor (DBI) and protoporphyrin IX. We have now demonstrated that several synthetic DBI peptides--analogues to naturally processed human DBI (H-DBI) fragments--differ from protoporphyrin IX in the manner in which they displace [3H]PK 11195 and [3H]4'CD from binding sites associated with intact and cell-free lymphocyte preparations. In particular, the peptide fragments DBI37-80 and DBI37-70 displaced [3H]PK 11195 and [3H]4'CD with higher affinity from their binding sites on intact lymphocytes (Ki approximately 3-5 microM) than from the sites in the cell-free preparation (Ki approximately 20 microM). In contrast, protoporphyrin IX displaced [3H]PK 11195 and [3H]4'CD with higher affinity in the cell-free preparation (Ki - 0.4 microM) than in intact lymphocytes (Ki > 50 microM). Because DBI peptide fragments and protoporphyrin IX do not readily penetrate the plasma membrane of lymphocytes, our results suggest the existence of binding sites located both on the external face of the plasma membrane and intracellularly. The plasma membrane binding sites, recognized essentially only by DBI fragments, are termed here plasma membrane DBI receptors (PDRs). In contrast, the intracellular binding sites, recognized by both DBI fragments and protoporphyrin IX, are presumably located on mitochondria and are termed mitochondrial DBI receptors (MDRs). Immunohistochemical electronmicroscopic studies with antibodies to the synthetic peptide fragments 62-76 of the rat MDR support the hypothesis that PDRs are expressed on lymphocyte plasma membranes.

Amino Acid Sequence↗
PubMed1993

Cytoprotective drugs in the prevention of ethanol-induced experimental gastric mucosal damage: a morphological study.

Various so-called "cytoprotective" agents (sucralfate, carbenoxolone, 16,16-dimethyl-PGE2, sulglycotide and Maalox TC) have been tested on rats, with the aim of quantifying their capability to prevent ethanol-induced gastric mucosal damage. Rats fasted for 48 hours received 1 ml of 80% ethanol by oral gavage, after prior oral treatment with placebo or one of the above-mentioned drugs u.i.d. for 5 consecutive days. Six hours after ethanol administration, the animals were sacrificed and the stomach was removed and processed for computerized macroscopic assessment of the damaged surface and for structural (light microscopy) and ultrastructural (scanning and transmission electron microscopy) studies. The results obtained demonstrate that ethanol injury caused extensive mucosal necrosis of the glandular region of the stomach, an event that was effectively reduced in rats treated with 16,16-dm-PGE2, carbenoxolone or sulglycotide. These drugs appeared to preserve the mucosa, with morphology comparable to that of normal noninjured rats - in contrast to the other drugs investigated. These data confirm the cytoprotective properties of sulglycotide in particular, which was the most potent agent for preventing the development of ethanol-induced acute lesions of the gastric mucosa.

16,16-Dimethylprostaglandin E2↗
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↗