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Biomedical subjects

A Fabbri

Publications and source records attributed to A Fabbri.

At least 145 records · Page 8Linked to original sources
PubMed1994

Kinetics of hepatic amino-nitrogen conversion in ageing man.

Previous studies have shown that hepatic function, quantitatively measured by dynamic liver function tests, progressively declines with ageing. Urea synthesis is a specific process taking place in the liver; a reduced urea synthesis in response to a protein-rich metal has previously been demonstrated in the elderly, but the process has never been standardized in relation to amino acid supply. We measured the hepatic conversion of alpha-amino nitrogen into urea nitrogen in response to alanine infusion in 32 subjects, with normal routine liver and renal function tests and without evidence of previous hepatic disorders, belonging to three different age-groups (< or = 55 years, 56-70, > or = 71). The functional hepatic nitrogen clearance was reduced on average by 20% in subjects aged 56-70 years, and by 30% in subjects over 70 years old in comparison to the age-group under 55 years (ANOVA: P = 0.0001), and significantly correlated with age (r = -0.684). No sex differences were observed on the effects of age on hepatic clearance. Also, liver volume, measured by ultrasonography, was reduced with advancing age, but the age-related decrease in hepatic nitrogen conversion was not primarily dependent on decreased liver volume. The measurement of functional hepatic nitrogen clearance has already been validated as a quantitative liver function test in clinical hepatology. In keeping with previous studies, the age-related decline in hepatic nitrogen conversion points to a decreased functional capacity of the ageing hepatic parenchyma.

Aged↗
PubMed1994

Lowering effects of a preparation containing fibres and lactulose on glucose and insulin levels in obesity.

The short-term metabolic effects of a dietary supplementation of biscuits containing raw fibre and lactulose (Fiberlac, Bracco) on circadian glucose, insulin and amino acid concentrations were studied in 10 obese patients in a crossover comparison. The biscuits (3 at breakfast, 4 at lunch and 4 at evening meal; approximately 10 g total dietary fibre, 2 g raw fibre, 8.25 g lactulose) were randomly substituted for an equicaloric part of a diet containing 20-22 kcal per kg ideal body weight under strict medical surveillance. Blood glucose in response to meal, as well as mean concentration throughout the day was lower during fibre supplementation. Also mean insulin was halved, and the insulin response to meals was blunted by 100-250 pmol/L. The plasma amino acid response to meals was increased, possibly in relation to decreased insulinemia. The data show a remarkable metabolic effect of the preparation in obese patients, without any further dietary restriction. The clinical effects and compliance remain to be determined in long-term studies, and in other states of glucose-intolerance, e.g. liver cirrhosis.

Adult↗
PubMed1994

[The concept of stress and the role of hypothalamic and extra-hypothalamic corticotropin-releasing factor (CRF) in the integration of the neuroendocrine and immune responses. Clinical and experimental aspects].

Several evidences suggest the existence of a bidirectional link between the immune and neuroendocrine systems. This relationship explains how a "non cognitive" stimulus (as antigen) can activate the neuroendocrine axis through the inflammatory substances (cytokines) in the same manner as a stress response. A disregulation of this response can determine the basis for a pathological situation. The key-peptide of the stress response is hypothalamic CRF, though also extra-hypothalamic sources, such as the cells of the immune system, are present and could play an important role in the peripheral regulation of stress response.

Adrenocorticotropic Hormone↗
PubMed1993

Corticotropin-releasing factor: an antireproductive hormone of the testis.

Corticotropin-releasing factor (CRF), the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). CRF is secreted by the Leydig cells of the testis and acts through high-affinity receptors at the Leydig cell membrane as a potent negative regulator of LH action, inhibiting gonadotropin-induced cAMP generation and androgen production. CRF is also a primary stimulus of beta-endorphin secretion by the Leydig cells, which in turn exerts paracrine inhibition of FSH action in the tubular compartment of the testis through high-affinity receptors in the Sertoli cells. CRF action in the Leydig cells involves a pertussis toxin-insensitive guanyl nucleotide regulatory unit. In contrast to CRF receptors in the brain, pituitary, and other peripheral tissues, those in the Leydig cell are not coupled to Gs. The inhibitory action of CRF in the Leydig cell is exerted through protein kinase C, at the level of the catalytic subunit of adenylate cyclase. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2 receptors. Serotonin acts on 5HT2 receptors in the Leydig cell to stimulate CRF secretion via a pertussis toxin insensitive G-protein and presumably through activation of phosphoinositide hydrolysis. The diversity of the biochemical responses to CRF and 5HT2 receptor activation (i.e., inhibition of adenylate cyclase at the cytoplasmic aspect of the cell membrane vs. stimulation of CRF release from secretion granules) may reflect the stimulation of different protein kinase C isoenzymes. The LH-->5HT-->CRF inhibitory loop serves to continuously buffer the stimulation of androgen production by gonadotropin. 5HT, the immediate stimulus of testicular CRF secretion, is released during stress and is locally increased in the testis in pathological conditions associated with impaired testicular function (i.e., orchitis, varicocele). Also, propranolol, the beta-adrenergic antagonist frequently used in the control of blood pressure in patients with hypertension and often associated with impotence, acts via a serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH-induced cAMP production and steroidogenesis in cultured Leydig cells. These basic studies of 5HT and CRF are relevant to the pathogenesis of testicular dysfunction and for the development of antagonist therapies to block CRF production and its local antireproductive effects.

Animals↗
PubMed1993

Lactitol in treatment of chronic hepatic encephalopathy. A meta-analysis.

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disaccharides in the treatment of encephalopathy: pooled odds ratio was 0.83, 95% confidence interval was 0.38-1.82. Results were not sensitive to the use of alternative methods of counting and attributing events in these trials. Patients experienced fewer side effects during treatment with lactitol, but the pooled odds ratio was not statistically significant. In all studies lactitol was considered more palatable. Clinical effectiveness of lactitol, in long-term treatment of chronic encephalopathy, is similar to those of lactulose. It seems that lactitol has lower side effects than lactulose. Future RCTs with a double-blind design could be mainly aimed at evaluating the side-effect profile of the two disaccharides.

Chronic Disease↗
PubMed1993

Mechanical assist device for right ventricular failure after acute aortic dissection.

Acute myocardial ischemia and infarction due to retrograde coronary artery dissection are uncommon complications after ascending aortic dissection. A case of acute aortic dissection with massive right ventricular failure successfully treated by replacement of the ascending aorta and postoperative right ventricular mechanical support is presented. Although mechanical assistance may be hazardous after ascending aortic replacement, because of the need of anticoagulation, it represents a valid therapeutic option when severe right ventricular failure due to acute myocardial infarction ensues.

Acute Disease↗
PubMed1993

Hepatic conversion of amino nitrogen to urea nitrogen in hypothyroid patients and upon L-thyroxine therapy.

Conflicting studies have been reported regarding the influence of thyroid hormones on hepatic nitrogen metabolism and liver metabolic activity. We studied urea N synthesis rate (UNSR), functional hepatic N clearance (FHNC), galactose elimination capacity, and antipyrine clearance in six hypothyroid female patients before and after achievement of a stable euthyroid status. In both conditions, UNSR measured at intervals in response to constant alanine infusion was linearly related to the average alpha-amino N concentrations. In the hypothyroid state, peak UNSR was decreased by 31% in comparison with values measured in euthyroidism, which were in the normal range. FHNC (ie, the slope of the linear relation between UNSR and blood alpha-amino N concentration) is a measure of the kinetics of the process of hepatic amino N to urea N conversion; it was 19.8 +/- 4.0 L.h-1 in hypothyroid patients and increased to normal values after L-thyroxine replacement (30.4 +/- 3.3 L.h-1, P < .01; normal values > 25 L.h-1). Hepatic microsomal and cytosolic activities (antipyrine clearance and galactose elimination) were normal in hypothyroid patients and did not change significantly after therapy. Our data show a specific defect in hepatic handling of amino acids in hypothyroid patients, leading to reduced alpha-amino N to urea N conversion, in the absence of any detectable impairment in different hepatic metabolic activities.

Adult↗
PubMed1993

Sodium-lithium countertransport activity in red blood cells of patients with IgA nephropathy.

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

Adolescent↗
PubMed1993

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

Aged↗
PubMed1993

Mechanical support for decompression of the left ventricle in repair of ischemic cardiac rupture.

Acute cardiac rupture is often a lethal complication of transmural myocardial infarction. A case of successfully treated left ventricular free wall rupture is described. Preoperative hemodynamic stabilization was achieved by intraaortic balloon counterpulsation. A BioMedicus left ventricular assist device was used intraoperatively and postoperatively to obtain long-term intraventricular decompression to allow for suture repair of friable myocardium.

Aged↗
PubMed1993

Serotonergic inhibition of rat Leydig cell function by propranolol.

The beta-adrenergic antagonist propranolol binds to serotonin (5HT) receptors (5HT1B > 5HT1A > 5HT2) in brain membranes. We have recently demonstrated that 5HT acts through 5HT2 receptors in rat Leydig cells to release CRF, which, in turn, inhibits hCG-stimulated cAMP production and steroidogenesis. These observations prompted us to study the effects of propranolol on CRF secretion and cAMP and testosterone production in cultured rat Leydig cells. Treatment with (-)propranolol increased CRF release and inhibited basal and hCG-stimulated cAMP and steroidogenesis, with effects evident at 0.1 microM, an IC50 of 6 microM, and reduction of stimulated levels to near basal at 100 microM. These effects of the drug were prevented by pretreatment of cultures with the 5HT2 receptor antagonist ketanserin or a CRF antagonist or antiserum. Furthermore, propranolol increased the level of 5HT in the incubation medium of cultured Leydig cells. The (+)isomer of propranolol had minor effects on these parameters. Increasing concentrations of (-)propranolol displaced the binding of [125I] +/- 1-[2,5-dimethoxy-4-iodophyryl]-2-amino propane hydrochloride (DOI), a selective 5HT2 ligand, to Leydig cell membranes (IC50, 0.2 microM), and (+)propanolol showed weaker potency. The inhibitory actions of propranolol were exerted through its blockade of the Leydig cell 5HT2 low affinity receptor, which has functional properties of an autoreceptor, with consequent increases in 5HT and stimulation of CRF release through 5HT action at the high affinity site. The serotonergic actions of propranolol were prevented by DOI, an inhibitor of 5HT actions at the high affinity site. In addition, the propranolol-induced blockade of the low affinity site further increased the cAMP and steroidogenic responses to gonadotropin over those observed with DOI treatment alone. These studies demonstrate that propranolol acts as an antagonist at the Leydig cell low affinity 5HT2 receptor and stimulates CRF release via a serotonergic mechanism, with consequent inhibition of cAMP generation and steroidogenesis. This serotonergic action of the drug could contribute to the impairment of sexual function reported during propranolol treatment in man.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Serotonin secretion from rat Leydig cells.

In rat Leydig cells, serotonin (5HT) binds to 5HT2 receptors and stimulates the secretion of CRF which in turn acts as an inhibitor of gonadotropin-induced cAMP formation and androgen production. In the present study we defined the regulation of 5HT secretion in cultured Leydig cells. Adult Leydig cells secreted considerable quantities of 5HT (100-150 pg/10(6) cells per 10 min). The release of 5HT was acutely stimulated by hCG (ED50, 1.1 pM) with maximal stimulation at 10 pM hCG (160%). Forskolin also increased (+220%) 5HT release from cultures (ED50, 50 nM) while TPA was much less effective (+20%), indicating a major role for cAMP in gonadotropin-induced 5HT release. This was confirmed by the finding that 8-Br cAMP (1 mM) was an effective stimulus of 5HT release (+360%). Similar increases of 5HT release by hCG were observed in the absence of extracellular Ca2+. However, ionomycin was a potent stimulus of 5HT release, indicating that elevation of cytoplasmic [Ca2+] could also induce amine secretion. The 5HT content of Leydig cells ranged from 300 to 350 pg/10(6) cells, and decreased during stimulation of 5HT release. Also, immunohistochemical studies revealed specific staining of 5 HT in interstitial cells of the adult rat testis. These studies demonstrated that rat Leydig cells contain and secrete 5HT, and that 5HT release is stimulated by gonadotropin acting primarily through a cAMP-mediated mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
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↗
PubMed1992

Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated.

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.

Adult↗
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

Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients.

Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients.

Adolescent↗
PubMed1992

Effect of S-adenosyl-L-methionine administration on plasma levels of sulphur-containing amino acids in patients with liver cirrhosis.

An impaired transsulphuration pathway has been described in patients with liver cirrhosis. The defective metabolic step is located at the site of S-adenosyl-L-methionine (SAMe) formation from methionine. In a placebo-controlled study, we measured the fasting plasma levels of sulphur-containing amino-acids in cirrhotic patients with hypermethioninemia and/or severe hepatocellular failure, during treatment with exogenous SAMe (1.2 g i.v. for 3 days, followed by an oral administration of 1.2 g for an additional 30 days; 8 cases) or saline and placebo tablets (8 cases). All subjects were initially treated during hospital admission, and completed the oral study as out-patients. In patients given SAMe, long-term treatment doubled the plasma concentration of the secondary sulphur-containing amino acid cystine (from 36 [SD 18] mumol.l(-1) to 67 [36]) and taurine (from 42 [13] mumol.l(-1) to 89 [33]), which were on average low-normal at baseline, without any change in the concentration of methionine, of neutral amino acids, and of polyamines. No changes in plasma amino acids were observed in the control group. Two-factor, repeated measures of analysis of variance revealed differences between SAMe- and placebo-treated patients, consistent with an effect of long-term SAMe administration on secondary sulphur-containing amino acids. The potential therapeutic advantage of such treatment remains to be determined in clinical studies.

Journal Article↗