Biomedical subjects

A Fabbri

Publications and source records attributed to A Fabbri.

At least 163 records · Page 9Linked to original sources

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

Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy.

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between 'familial' and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.

Adolescent↗

PubMed1992

Regulation of corticotropin-releasing factor secretion from Leydig cells by serotonin.

CRF is produced in the Leydig cells and acts as a negative autocrine regulator of Leydig cell function. To clarify the hormonal control of CRF secretion by Leydig cells, we evaluated the participation of serotonin (5HT) and serotonin agonists in the release of CRF from Leydig cells and their effects on hCG-induced cAMP generation and steroidogenesis. Serotonin stimulated CRF secretion up to 4-fold above basal levels and inhibited basal and hCG-stimulated cAMP generation and testosterone production (ID50, 1 nM). The inhibitory action of 5HT was prevented by a CRF antibody and the alpha-helical CRF-(9-41) antagonist. The selective 5HT2 receptor agonist (+-)1-[2,5-dimethoxy-4-iodophyryl]2-amino propane hydrochloride (DOI) also stimulated CRF secretion and inhibited hCG-stimulated cAMP generation and testosterone production to control levels (ID50, 7 microM). Serotonergic 5HT1A, 5HT1B/1C, 5HT1D, and 5HT3/5HT2 agonists were less effective inhibitors of hCG-stimulated cAMP and testosterone production, while agonists for the 5HT3 receptor had no effect. [125I]DOI binding studies in Leydig cells demonstrated two sets of receptors with Kd values in the nanomolar and micromolar range, with low and high capacities, respectively. The low affinity site differed from that of brain receptors (Kd, 4.2 nM) and displayed higher binding capacity (50-fold). The selective 5HT2 receptor antagonist ketanserin prevented CRF stimulation and blocked the inhibitory actions of 5HT and DOI, while the alpha 1-adrenergic antagonist prazosin had no effect. Also, treatment of cells with ketanserin increased sensitivity to hCG and raised maximal cAMP and testosterone production. 5HT was a more effective stimulus than hCG in stimulating CRF secretion, and gonadotropin-induced CRF release was inhibited by ketanserin. Inhibitory effects of exogenous CRF were demonstrable after blockade of 5HT action by ketanserin. The inhibitory actions of 5HT were unaffected by pertussis and cholera toxins and were reversed by the addition of 8-bromo-cAMP. These results demonstrate that 5HT acts on 5HT2 receptors in Leydig cells that are distinct from those in the brain to stimulate CRF secretion through a pertussis toxin-insensitive G-protein. This action of 5HT is predominantly mediated by the low affinity 5HT2-binding site and requires full occupancy for maximal CRF stimulation, indicating the absence of spare receptors. 5HT-stimulated CRF inhibits basal and hCG-induced cAMP generation and steroidogenesis. Furthermore, 5HT mediates the stimulatory action of LH/hCG on CRF secretion from Leydig cells and, thus, participates in a negative autoregulatory loop to limit the testosterone response to the gonadotropic stimulus.

Amphetamines↗

PubMed1992

Growth hormone-releasing hormone is produced by rat Leydig cell in culture and acts as a positive regulator of Leydig cell function.

Rat GH-releasing hormone (GHRH), mainly contained in hypothalamic neurons, has also been identified in several extraneural tissues, including the gastrointestinal tract, placenta, ovary, and testis. In the testis, GHRH mRNA is ontogenically regulated, and GHRH immunoreactivity can be observed in interstitial cells and tubules, suggesting an intratesticular role for the peptide. Leydig cells in culture are able to produce hypothalamic releasing hormones, i.e. CRH, which acts as an autocrine negative regulator of Leydig cell function. In this study we investigated whether GHRH is present in Leydig cells and evaluated the role of the peptide in Leydig cell function. Adult Leydig cells in culture produced considerable amounts of immunoreactive GHRH [23.9 +/- 2.1 (+/- SE) pg/10(6) cells.30 min], and the release of the peptide was acutely stimulated by hCG. HPLC analysis of GHRH in media from basal and hCG-treated cultures showed the presence of a single peak eluting at the same retention time as that of hypothalamic rat GHRH. Radioligand binding and activation studies revealed a common receptor for vasoactive intestinal peptide (VIP) and rat GHRH in Leydig cell membrane. Specific binding of [125I]VIP to Leydig cell membranes showed the presence of a single site, with high affinity and low binding capacity. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP > rat GHRH > secretin > human GHRH. In cultured Leydig cells, GHRH and VIP stimulated cAMP production, consistent with coupling of the receptor to the adenylate cyclase system. VIP displayed a lower ED50 than GHRH in stimulating cAMP production (P < 0.01), comparable with the higher binding potency of this peptide. No additive effects of VIP- and GHRH-stimulated cAMP generation were observed, suggesting that both peptides compete for the same receptor protein. GHRH and VIP had no effect on basal steroidogenesis, indicating a lack of tonic actions and compartmentalization of the peptides' effect. On the other hand, GHRH acted as a potentiator of the acute gonadotropin stimulation of testosterone production and cAMP generation. [125I]hCG binding to the Leydig cells in culture showed that GHRH was unable to affect the number or affinity of binding sites for hCG, indicating that the GHRH-sensitizing effect on LH action is beyond the level of gonadotropin binding and possibly is through the facilitation of LH receptor coupling functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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↗

PubMed1992

Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.

Administration, Oral↗

PubMed1991

Nociceptive quality of the orbicularis oculi reflexes as evaluated by distinct opiate- and benzodiazepine-induced changes in man.

The corneal reflex and the three components of the blink reflex (R1, R2, and R3) were recorded electromyographically in volunteers. The area of these responses was measured before and after administration of the narcotic-analgesic fentanyl (1.5 mg i.m.) and its antagonist naloxone, and after administration of the benzodiazepine diazepam (10 mg i.v.) and its antagonist flumazenil. Saline was given as a control placebo. The corneal reflex was 71% reduced by fentanyl, 43% by diazepam. R1 was 35% reduced and R2 was 60% reduced by diazepam. R3 was abolished by both drugs. Whereas the fentanyl-induced changes were completely reversed by naloxone, the diazepam-induced changes were only partly reversed by flumazenil. The corneal reflex appears to be a 'nociceptive' reflex under all points of view. Recording of the orbicularis oculi reflexes in man may be valuable in the evaluation of central-acting neurotropic drugs.

Adult↗

PubMed1991

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients.

The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile. Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine less than or equal to 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated. Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure greater than or equal to 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 +/- 17; 241 +/- 12 and 211 +/- 11 mumol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration greater than 200 mg/dl and/or plasma triglycerides greater than 172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 +/- 14; 226 +/- 12 and 211 +/- 11 mumol/liter RBC/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Effect of physical exercise on one-sample antipyrine clearance.

Moderate physical exercise for a few hours is not expected to reduce the hepatic elimination of drugs exhibiting capacity-limited metabolism (low-clearance drugs such as antipyrine). However, previous studies have shown that antipyrine half-life, measured by the multiple-sampling technique, is increased by exercise. A simplified one-sample procedure for antipyrine clearance determination is increasingly being used as a liver function test. The effects of exercise on this measurement have never been evaluated. We measured antipyrine clearance, using the one-sample, simplified procedure in a group of 50 young Italian army soldiers, while at rest and during a 6 hour march in the mountains (extra energy expenditure: 7.43 kjoule per min). Mean antipyrine clearance was on average 46.6 (SD 10.2) ml/min (range 30.5-65.4) while resting, and 46.2 (10.5) (range 25.5-64.8) while exercising (not different). No specific advice regarding physical exercise is needed whenever liver function is measured in outpatients by the one-sample, simplified antipyrine clearance test.

Adult↗

PubMed1991

Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method.

The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.

Adult↗

PubMed1990

A novel mechanism of action of corticotropin releasing factor in rat Leydig cells.

We have recently demonstrated the presence in the rat Leydig cells of a corticotropin releasing factor (CRF) receptor and an inhibitory action of the peptide on human chorionic gonadotropin (hCG)-induced cAMP generation and steroidogenesis. The inhibitory action of CRF was unaffected by pertussis toxin and was completely reversed by 8-bromo-cAMP (Ulisse, S., Fabbri, A., and Dufau, M. L. (1989) J. Biol. Chem. 264, 2156-2163). In this study, we have evaluated the participation of protein kinase C in CRF action in the Leydig cells and the level of the gonadotropin signal pathway affected by CRF. Binding of 125I-labeled ovine CRF to Leydig cell membranes was reduced by GTP and guanyl-5'-yl imidodiphosphate (Gpp(NH)p), in a dose-dependent manner. Phorbol 12-myristate 13-acetate, like CRF, caused time-dependent inhibition of hCG-induced cAMP generation and steroidogenesis. This inhibitory action was reversed by 8-bromo-cAMP. Both CRF and 12-O-tetradecanoylphorbol-13-acetate did not affect 125I-hCG binding. No additive effects of CRF and the phorbol ester were observed in these studies. CRF caused a rapid translocation of protein kinase C in Leydig cells. Preincubation of cells with protein kinase C inhibitors or TPA-induced depletion of protein kinase C prevented the inhibitory actions of CRF and TPA. CRF and TPA were able to inhibit the stimulation of cAMP and testosterone production by cholera toxin and forskolin. Adenylate cyclase stimulation by Gpp(NH)p, luteinizing hormone + Gpp(NH)p, and NaF in crude membranes or by forskolin and manganese in solubilized membranes, prepared from CRF- and TPA-treated cells, was also markedly inhibited. We conclude that CRF receptors interact with a pertussis toxin-insensitive G protein (possibly Gp) in the Leydig cell and that the inhibitory action of CRF on Leydig cell function is exerted mainly on the catalytic subunit of adenylate cyclase through a direct or indirect action of protein kinase C.

Adenylyl Cyclases↗

PubMed1990

Immunohistochemical localization of growth hormone-releasing hormone in human gonads.

Human gonads were examined for the presence of ir growth hormone-releasing-hormone. We demonstrated the presence of immunostainable cells both in ovarian and in testicular tissue using a non-crossreactive anti-GRH antiserum and the immunoperoxidase detection technique. In ovaries from ovulating women, GRH immunoreactivity was localized in the corpora lutea; granulosa cells, theca cells and cells of primary follicles did not stain. In premenopausal ovaries, staining was detectable in scattered luteinized stromal cells. In testes from post-puberal men GRH immunoreactivity was localized in the Leydig cells; cells of the germinal epithelium did not stain. These results demonstrate the presence of GRH in human gonads and suggest that this peptide may exert regulatory function at the testicular and ovarian levels.

Female↗

PubMed1990

The effect of fresh human serum on ofloxacin bactericidal activity.

We have studied the possibility of an increase in ofloxacin bactericidal activity when it is combined with fresh human serum. The tested strains were 10 clinical isolates of Klebsiella pneumoniae. From among our strains 5 were susceptible to serum bactericidal activity and 5 were found to be resistant. We selected two serum concentrations (15 and 35%) to test against susceptible strains and two (55 and 75%) to test against resistant strains in combination with the minimum inhibitory concentration (MIC), 1/2MIC and 1/4MIC of ofloxacin. The results show a slight variability among the tested strains depending on microbiological characteristics of single strains, however, the serum + ofloxacin combination was advantageous. Only one exception was observed: a resistant strain that had an increased survival percentage against ofloxacin and serum in combination.

Blood↗

PubMed1990

Synthesis of urea after a protein-rich meal in normal man in relation to ageing.

An age-related decline in the functional capacity of the liver has been repeatedly demonstrated by means of dynamic tests. We measured the urea-N synthesis rate in response to a protein-rich meal in 24 healthy subjects divided into three age-groups (less than or equal to 55 years, 56-70 years; greater than or equal to 71 years). No differences were observed in the basal state. The peak urea synthesis and the mean urea synthesis in the 5 hours after the meal were blunted with increasing age, and a negative correlation was present between mean or peak urea synthesis and age (r = -0.572 and r = -0.541, respectively). No differences in basal and post-meal total alpha-amino-nitrogen or individual plasma amino acids were observed. Hormone responses were similar. Galactose elimination capacity was also reduced with increasing age, and correlated with mean and peak urea synthesis after a protein mean (r = 0.640 and r = 0.591, respectively). These data suggest that the capacity of the liver to produce urea in response to a protein-rich meal is reduced in the elderly in relation to a decreased functional liver cell mass.

Age Factors↗

PubMed1990

Antiproteinuric effect of angiotensin-converting-enzyme inhibitors in patients with primary glomerular disease and normal renal function.

The antiproteinuric efficacy of angiotensin-converting-enzyme inhibitors (ACEI) has been extensively investigated in patients with several types of nephropathy, but there are few data on the use of ACEI in patients with primary glomerular disease without renal function impairment. We evaluate the effect of long-term therapy with captopril on arterial pressure and proteinuria in 13 patients with primary glomerular disease, selected on the following criteria: persistent proteinuria greater than 600 mg/day, serum creatinine less than or equal to 1.5 mg/dl, no dietary restriction or antihypertensive or immunosuppressive therapy for at least 9 months prior to enrolment. Ten of 13 patients were normotensive. The treatment with captopril induced an early and persistent decrease in proteinuria (41%), and a significant increase in serum albumin. We did not find a significant correlation between changes in MAP and changes in protein loss or between variations in serum creatinine and in proteinuria. Our results demonstrate that captopril is effective in reducing proteinuria in patients with primary glomerular disease with normal renal function. Since the antiproteinuric effect is not associated to a concomitant decrease in arterial pressure, we presume that it might be due to a specific intrarenal action of captopril.

Adolescent↗

PubMed1990

Analysis of the deterioration rates of liver function in cirrhosis, based on galactose elimination capacity.

The prognosis of cirrhotic patients may depend on their liver function, but very few data are available to predict life expectancy in individual subjects on the basis of their liver function tests. The yearly changes in liver function, based on galactose elimination capacity (GEC), were retrospectively analyzed in 76 cirrhotic patients. The first GEC measurement had always been performed at the time of diagnosis. From that time on, mean GEC changes (in mmol/min per year) were +0.13 [SD 0.60] in the 1st year (range: +1.42/-1.35), and -0.03 [0.30] in the 2nd year (P = ns). Only after 36 months could a significant deterioration in liver function be demonstrated, but GEC changes still ranged from +0.14 to -0.35. The trend in liver function was similar in patients with alcoholic and non-alcoholic cirrhosis, but in alcoholics a favourable effect of abstinence was proved. In individual subjects, 2 consecutive GEC measurements, at least 6 months apart, failed to predict the following GEC values. The coefficients of determination between expected and measured GEC or delta GEC were 0.13 and 0.36, respectively (n = 58). When forecasting was limited to 2 years (n = 38), still only 31% and 55% of GEC values and delta GEC variance was predictable on the basis of preceding GEC values. The study shows that no definite trends in liver function deterioration rates can be observed in cirrhosis. This limits the usefulness of liver function tests in predicting prognosis in cirrhotic patients.

Adult↗

PubMed1990

Do calcium channel blockers have any influence on the immunological status of renal graft recipients on ciclosporin therapy?

We have assessed the peripheral distribution of T cells, using the monoclonal antibodies OKT3, OKT4, OKT8 and LEU7 and the proliferative response to phytohaemagglutinin (PHA), in 10 renal transplant recipients. In each patient, the immunological pattern was evaluated twice, both before and after 1 month of calcium antagonist (calcium channel blockers, CaA) treatment. During treatment with CaA, we have observed both a significant decrease in the mitogenic response to PHA and a significant increase in OKT8 cells. Our data support the hypothesis that CaAs per se may have an immunomodulatory effect on T cell distribution independently of changes in ciclosporin (CS) blood levels. These results could also provide a cellular basis for synergism between CS and CaA.

Adjuvants, Immunologic↗

PubMed1990

Corticotropin-releasing factor is produced by rat Leydig cells and has a major local antireproductive role in the testis.

Cultured rat Leydig cells secreted considerable amounts of corticotropin-releasing factor (CRF). A major stimulus for Leydig cell-derived CRF was the trophic hormone LH/hCG, which released the peptide in a dose dependent fashion. Incubation of Leydig cells with a CRF antagonist revealed tonic suppression of basal and hCG-stimulated testosterone production by endogenously produced CRF. These findings demonstrate that CRF acts via functional Leydig cell receptors to exert autocrine inhibitory actions on Leydig cell steroidogenesis. In the testis CRF acts as an antireproductive hormone and as a major local inhibitory regulator of Leydig cell function.

Animals↗