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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

Kinetics and brain uptake of S 9795, a new xanthine derivate, in rats.

The relationships between plasma and brain concentrations of S 9795 and its main metabolites after single intravenous doses of S 9795 were examined in rats by high-performance liquid chromatography with UV detection. S 9795 disappeared from plasma and brain almost in parallel, with comparable elimination t1/2 of about 0.8 h, regardless of the dose administered. The volume of distribution was high (about 3 1/kg) but total clearance was also high (about 40 ml/min/kg) and this explains the relatively short plasma and brain t1/2 of the drug in the rat. Among the possible metabolites examined, the N-dearylated metabolite S 10238 rapidly appeared in both plasma and brain. Thereafter, S 10238 was likewise eliminated in parallel from both compartments, although at a slower rate (t1/2 of about 1.4 h) than its parent compound. Norcyclizine, a metabolite resulting from cleavage of the parent drug side-chain, was detected only in the brain and only at the highest dose tested. The brain AUC to plasma AUC ratio was slightly less than 1 for S 9795, about 0.1 for S 10238 and possibly more than 2 for norcyclizine, this latter being present in rat plasma at concentrations below the limits of sensitivity of the method (0.08 nmol/ml). The results indicate that S 9795 and some of its metabolites enter the central nervous system, although to different extents, and support the hypothesis that the lack of central effects of S 9795 is probably the consequence of the poor adenosine brain receptor antagonism by this compound.

Animals↗
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Morphine inhibits gastrointestinal transit in the rat primarily by impairing propulsive activity of the small intestine.

The effect of a single dose of morphine on small intestinal transit was studied in fasted rats by feeding a charcoal test meal either by stomach tube to normal animals or through a duodenal cannula to chronically implanted rats. The percentage of small intestine traversed by charcoal in 5 min was reduced by morphine (0.7 mg/kg s.c.) given 5 min before the meal to a similar extent in normal and implanted rats. In contrast administration of atropine (0.8 mg/kg s.c.) 30 min before the meal reduced charcoal transit only in normal rats fed the test meal by stomach tube. Inhibition of gastrointestinal transit in the rat by systemically administered morphine is mainly due to impaired small intestinal propulsion and does not depend to any significant extent on a direct action on the stomach delaying gastric emptying.

Animals↗
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Inhibition of gastrointestinal transit by morphine and FK 33-824 in the rat and comparative narcotic antagonist properties of naloxone and its N-methyl quaternary analog.

Morphine and the enkephalin-like peptide FK 33-824 given i.p. to rats potently inhibit gastrointestinal transit of a charcoal test meal, the doses inhibiting transit by 50% being respectively about 10 and 1 microgram/kg. These intestinal effects are opiate-specific, locally elicited and presumably involve the same action site since they are reversed by the "peripherally selective" narcotic antagonist N-methyl naloxone with apparent pA2 values of 7.34 and 7.10 respectively against morphine and FK 33-824. The calculated pA2 value for naloxone/morphine with the same in vivo test procedure (8.83) and the relative ability of naloxone and N-methyl naloxone to prevent 3H-etorphine binding to rat brain membranes (IC50 43 and 541 nM), indicate different potency ratios between the two narcotic antagonists in the in vitro binding cell-free system (about 1:10) and in vivo (about 1:30), but the latter ratio agrees with published findings in the isolated guinea pig ileum.

Animals↗
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Effects of a new calcium antagonist, Rec 15/2375, on cardiac contractility of conscious rabbits.

The new calcium antagonist Rec 15/2375, supposed to be selective for the vascular tissue, was compared to nifedipine, a non-selective agent that reduces blood pressure and impairs cardiac inotropism as well. Six rabbits, chronically catheterized and continuously monitored for systemic blood pressure, heart rate and the isovolumic contractility index dP/Tmax, were alternatively treated with Rec 15/2375 and nifedipine, according to a randomized cross-over design. Both drugs were given under either autonomically intact (AI) or suppressed (AS) heart function control, induced by cholinergic and beta-adrenoceptor blockade. The two agents reduced mean arterial blood pressure comparably and dose-dependently (P less than 0.01) under both experimental conditions (from 10 to 40%), thus causing heart rate to increase reflexly (P less than 0.01), similarly between drugs in AI rabbits, whereas the AS manoeuvre totally abolished such a response. Cardiac contractility, on the other hand, displayed opposing behaviour between the two drugs. Rec 15/2375 caused mild but significant (P less than 0.01) increases, which were similar at all doses (+10, +15%) and insensitive to the AS intervention, whereas nifedipine caused dose-dependent reductions (from -10 to -60%; P less than 0.01) of comparable intensity as mean blood pressure decrease in both protocols. We conclude that Rec 15/2375 effectively lowers blood pressure with no impairment, unlike nifedipine, of cardiac inotropism and we discuss the possibility that dP/dTmax may be increased as a result of the haemodynamic rearrangement following after-load reduction.

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Correlations between protein kinase C zeta signaling and morphological modifications during rat heart development and aging.

From birth to aging the heart undergoes functional changes reflecting biochemical and ultrastructural modifications which imply apoptosis. This is a physiological process resulting from genetic programs closely associated with development and aging. During development apoptosis eliminates redundant cells leading to heart remodeling, while during aging it eliminates damaged or exhausted cells. In the present paper we analyze some molecular mechanisms involved with heart morphological modifications, especially in the neonatal heart which displays different features in the subendocardial and myocardial area. The high number of subendocardial apoptotic cells and the inverted ratio of Bcl-2/Bax molecule expression in the two heart compartments led us to hypothesize a different metabolism in the myocardium as compared with subendocardium. Moreover, we propose that PKC zeta may mediate this different response by activating Nf-kB pathway and by maintaining the balance between hypertrophic growth and apoptosis involved with remodeling of neonatal heart. Further, we underline that in the aged heart, where this pathway is not activated, such balance is not maintained.

Aging↗
PubMedDate not supplied

Reduced quality of life in patients with chronic hepatitis C: effects of interferon treatment.

BACKGROUND: Quality of life is an area of increasing interest in hepatology. Studies, so far, have assessed quality of life in patients with chronic virus C-related hepatitis in relation to antiviral therapy by means of generic questionnaires. AIM: To measure quality of life in chronic hepatitis patients without cirrhosis by means of the Nottingham Health Profile questionnaire, a measure of "distress" in comparison with the Medical Outcome Survey SF-36, an index of well-being. PATIENTS: A series of 126 outpatients with chronic hepatitis; 37 on and 89 not on active interferon treatment. METHODS: The two questionnaires were used in random order. Clinical and laboratory data were also collected. The final score of any domain of the two questionnaires, for any individual patient, was compared to age-adjusted normal values obtained in 2 random samples of Italian population. RESULTS: Patients showed a significant modification of 3 domains of Nottingham Health Profile (Energy, Social Isolation and Physical Mobility) and 6 domains of SF-36. In relation to interferon treatment, the Nottingham Health Profile questionnaire was able to detect differences in Energy, Physical Mobility and Pain, which were modified only in treated patients. SF-36 did not show any differences in relation to treatment. In addition, the Nottingham Health Profile demonstrated that treated patients had a lower prevalence of concern for family life, possibly due to expectations of treatment itself. CONCLUSIONS: Active interferon treatment causes considerable distress in chronic hepatitis C patients, adding to the perceived change in health status caused by liver disease.

Adult↗
PubMedDate not supplied

Microenvironment and stem properties of bone marrow-derived mesenchymal cells.

Adult stem cells are self-renewing, pluripotent, and able to repopulate the tissue in which they reside. Cells endowed with these properties have been isolated from several tissues and an increasing number of reports provide evidence of their ability, following transplantation, to engraft host tissues other than those of their origin. In this setting, interest in the well-documented capacity of bone marrow stromal cells to undergo multilineage differentiation is growing. Neural and cardiomyogenic lineages have recently been proposed as additional differentiative pathways of these cells. However, culture conditions and inductive molecules can alter the behavior of bone marrow stromal cells and the microenvironment is critical for proper in vivo delivery. The maintenance of their stem properties and the possibility of reprogramming their commitment is a field of primary interest given the potential use of these cells in regenerative medicine. We discuss here how the microenvironmental cues, and the growth factors that physiologically govern commitment and subsequent differentiation, influence the properties of bone marrow stromal cells and modulate their engraftment into host tissues.

Bone Marrow Cells↗
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CT diagnosis of congenital intrapericardial masses.

Prior to the development of CT, cardiac and pericardiac masses were evaluated by chest roentgenography, angiocardiography, and echocardiography. In most cases preoperative diagnosis of a specific entity was impossible. Preoperative CT diagnosis of an intrapericardial developmental mass becomes possible because of the presence of fat, fat/fluid level, thick walled cysts, as well as globular calcifications, bones, teeth, water density fluid, and soft tissue. A report of a young woman with a ruptured and infected intrapericardial teratoma and an infant with an intrapericardial bronchial cyst is presented.

Adult↗
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Overview of randomized clinical trials of oral branched-chain amino acid treatment in chronic hepatic encephalopathy.

BACKGROUND: The role of oral branched-chain amino acid supplements in the prevention and treatment of chronic hepatic encephalopathy is not yet established, and conflicting opinions are expressed in authoritative textbooks. We aimed to review and pool the published controlled studies by means of meta-analytical techniques. METHODS: A computerized search of published papers identified nine studies, controlled against placebo, energy, alimentary proteins, or casein. Their quality score was calculated according to the protocol of Chalmers. The value of the portal-systemic encephalopathy index was chosen as main outcome, because of lack of more significant clinical outcomes. To cope with differences in trial design and data presentation, individual data were requested to authors. RESULTS: After 18 months, we received the individual data of only two studies, thus precluding any meta-analysis. Two studies, accounting for over 60% of total enrolled patients, were in favor of branched-chain amino acids. Their quality score was much better than that of the remaining seven negative small studies, carrying a significant risk of type II error. CONCLUSIONS: Based on the results of the two largest, long-term studies, the use of oral branched-chain amino acids in the prevention and treatment of chronic encephalopathy may only be proposed for patients with advanced cirrhosis, intolerant to alimentary proteins. Large, multicenter, long-term studies, considering more important clinical outcomes, are needed to provide definite answers to an aged question.

Adult↗
PubMedDate not supplied

Protein kinase C zeta regulation of hypertrophic and apoptotic events occurring during rat neonatal heart development and growth.

The development and growth of the rat heart implies hyperplasia, which stops at birth, and hypertrophy, allowing cardiac mass to grow in response to programmed genetic events along with to haemodynamic overload. Moreover, hypertrophy is accomplished to apoptosis which controls the final number of myocardial cells, deletes vestigial structures, and takes part in remodelling the organ. Since at the basis of all these processes, which lead to the complete development of the heart, the activation of specific signalling pathways underlies, attention has been addressed to the role played in vivo by Protein Kinase C zeta (PKC zeta) in regulating NF-kB signalling system and intrinsic mitochondrial apoptotic route at days 1, 4, 10 and 22 of rat life. In fact, a role has been assigned to PKC zeta in indirectly phosphorylating IKBa, which peaks between 10 and 22 days, through a IKK determining, in turn, NF-kB activation, concomitantly to cytochrome c/Apaf 1 co-localization in the cytoplasm and caspase-9/caspase-3 activation, which leads to the occurrence of apoptosis. Thus a key role for PKC zeta in regulating the hypertrophic and apoptotic events leading to establishment of complete function in rat neonatal heart is here suggested.

Animals↗
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Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients.

In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.

Adult↗
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Bone marrow stromal damage after chemo/radiotherapy: occurrence, consequences and possibilities of treatment.

High dose chemotherapy (CT) followed by bone marrow transplant (BMT) is increasingly used for the treatment of both hematological and solid neoplasms, but an understanding of its late consequences on the marrow microenvironment is still only at its beginning. It is in fact known that marrow stroma is damaged by high-dose cytotoxic therapy and by radiation exposure. However little is known on the extent of this damage and on the self-repair ability of the stroma. The damage of the stromal microenvironment affects the long-term stem cell engraftment and the maintenance of hemopoietic functions. Furthermore, marrow stroma also represents a progenitor compartment for endosteal osteoblasts, and therefore its damage implies alterations of bone metabolism. Indeed, osteoporosis has recently been recognized as a consequence, of BMT, but only a few studies have been performed to establish the functional status of the stromal compartment after treatment with cytotoxic drugs with or without total body irradiation (TBI) and its role in post-BMT sequelae.

Animals↗