Biomedical subjects

E Marchi

Publications and source records attributed to E Marchi.

At least 19 recordsLinked to original sources

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

Antithrombotic and thrombolytic activity of sulodexide in rats.

We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis-mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation.

Animals↗

PubMed1992

Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats.

Abnormal glycosaminoglycan metabolism is involved in the onset of anatomo-functional derangements in diabetic nephropathy, and determines the loss of glomerular basement membrane anionic charges leading to albuminuria. Glycosaminoglycan administration was shown to increase the negative electrical potential of the vessel wall, inhibit mesangial cell proliferation, which is an anatomical hallmark of diabetic nephropathy, and slow down the progression to uremia in subtotally nephrectomized rats, a model that shares some pathogenetic key events with diabetic nephropathy. Based on these considerations, we verified the effect of exogenous glycosaminoglycans on renal involvement in streptozotocin diabetic rats. Long-term administration of two glycosaminoglycans (low-molecular weight heparin and dermatan sulphate) prevented glomerular basement membrane thickening, glomerular anionic charge reduction, as well as the onset of albuminuria without affecting glomerular filtration rate and metabolic control of the disease. Our data demonstrate that the long-term administration of glycosaminoglycans has a favorable effect on morphological and functional renal abnormalities in diabetic rats.

Albuminuria↗

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↗

PubMed1990

Protein C deficiency in insulin-dependent diabetes: a hyperglycemia-related phenomenon.

In 30 insulin-dependent diabetic patients protein C (PC) antigen and PC activity were significantly lower than those of matched control healthy subjects. An inverse correlation between fasting plasma glucose and both PC concentration and activity was present in diabetics, while a direct correlation between PC concentration and PC activity was observed. Induced hyperglycemia in diabetic and normal subjects was able to decrease both PC antigen levels and PC activity, and heparin reversed in part this effect. In diabetic patients euglycemia obtained by insulin infusion restored to normal the depressed PC levels. Heparin did not alter both the basal PC concentration and activity in healthy controls. These data stress the major role of hyperglycemia in determining PC decrease in diabetics, and suggest that PC reduction is probably associated to hyperglycemia-enhanced thrombin formation.

Adult↗

PubMed1990

Evidence for a hyperglycaemia-dependent decrease of antithrombin III-thrombin complex formation in humans.

In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus.

Adult↗

PubMed1990

Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.

Antithrombins↗

PubMed1990

The role of hyperglycaemia-induced alterations of antithrombin III and factor X activation in the thrombin hyperactivity of diabetes mellitus.

Factor X concentration and factor X activation, antithrombin III anti-Xa activity and plasma concentration, and fibrinopeptide A were measured in 20 diabetic patients and 20 normal subjects. Although factor X activation (81.3 +/- 2.2 vs 97.3 +/- 2.1%, p less than 0.01; mean +/- SE) and antithrombin III activity (76.5 +/- 2.2 vs 96.3 +/- 1.8%, p less than 0.01) were reduced in the diabetic patients, fibrinopeptide A concentration was increased (3.7 +/- 0.4 vs 1.7 +/- 0.2 ng ml-1, p less than 0.01). The ratio of factor X activation to antithrombin III anti-factor Xa activity was increased in the diabetic patients (1.10 +/- 0.01 vs 1.01 +/- 0.02, p less than 0.01). Induced hyperglycaemia was able to mimic all these abnormalities, without changing factor X or antithrombin III concentration. The results suggest that in vivo hyperglycaemia produces a decrease of factor X activation, but at the same time increases fibrinopeptide A formation due to a greater decrease of antithrombin III anti-Xa activity.

Adult↗

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

Lymphocyte subsets in bronchoalveolar lavage fluid and in circulating blood in epidermoid bronchogenic carcinoma.

Alveolar macrophages, lymphocyte and granulocyte percentages, together with OKT3+, OKT4+, OKT8+ lymphocyte subsets and OKT4+/OKT8+ ratio, were evaluated in bronchoalveolar lavage (BAL) fluid and in peripheral venous blood (PVB) of neoplastic and nonneoplastic subjects, in order to assess these aspects of immunity in neoplastic disease and to find out if the modifications in the bronchoalveolar environment are correlated to the ones in the circulation blood. BAL was performed in 30 patients undergoing fiberoptic bronchoscopy to ascertain the presence of lung cancer. Twelve of them had positive findings for epidermoid bronchogenic carcinoma, while in the remaining subjects the diagnosis was not confirmed. The 30 examined subjects were then grouped according to their smoking habit. In PVB, no significant difference was seen between neoplastic and nonneoplastic subjects, whereas in BAL the neoplastic patients showed a significant increase of lymphocytes OKT3+ and OKT8+. This tends to confirm that PVB is not a good indicator of organ immunity and may justify the reduced activity of alveolar macrophages in subjects affected by bronchogenic neoplasia. Between smokers and nonsmokers, lymphocyte subsets showed more significant differences than between neoplastic and nonneoplastic subjects (decrease of T4+ lymphocytes, increase of T8+ lymphocytes and, therefore, reduction of T4/T8 ratio); there were also scalar variations in the three groups (smokers with cancer, smokers without cancer and nonsmokers without cancer). Thus, the possible autonomous role of cigarette smoke and the presence of neoplasia in the immunity alterations of the alveolar environment with final joint effects were confirmed. These data may indicate a possible correlation between cigarette smoking, immunological alterations in BAL and the onset of bronchogenic carcinoma.

Adult↗

PubMed1990

Evidence for a reduced heparin cofactor II biological activity in diabetes.

A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.

Adult↗

PubMed1990

Comparative efficacy and tolerability of clarithromycin and amoxycillin in the treatment of out-patients with acute maxillary sinusitis.

The efficacy and tolerability of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in an open, Phase III multi-centre study. Sixty-one out-patients (40 males, 21 females) received clarithromycin (two 250 mg tablets twice daily) and 59 (34 males, 25 females) out-patients received amoxycillin (two 500 mg capsules twice daily). Fifty-seven and 47 patients in the clarithromycin group were evaluable for clinical efficacy and bacteriological effectiveness, respectively. In the amoxycillin group, 57 and 40 patients were evaluated for clinical efficacy and bacteriological effectiveness, respectively. Body temperature, bacteriological culture results, blood and urine chemistries, and clinical signs and symptoms were evaluated prior to drug administration, between Days 4 to 6 and between Days 9 to 11 of treatment, and within 48 hours and, if required, 6 weeks after the end of treatment. Clinical signs and symptoms improved significantly (p less than 0.001) in both treatment groups. When evaluated within 48 hours after the end of treatment, there was no significant difference between the clinical success rate for clarithromycin (91%) and amoxycillin (84%) nor in the number of patients whose original pathogen was eradicated (89% clarithromycin, 93% amoxycillin). Six patients reported adverse events, 2 with clarithromycin (urticaria, gastro-intestinal) and 4 with amoxycillin (2 urticaria, 2 gastro-intestinal). Clarithromycin was comparable to amoxycillin with respect to clinical efficacy and tolerability and offers a useful addition to the available therapies for the treatment of acute maxillary sinusitis.

Administration, Oral↗

PubMed1990

Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

Adult↗

PubMed1989

Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

Adult↗

PubMed1989

Hyperglycemia-conditioned increase in alpha-2-macroglobulin in healthy normal subjects: a phenomenon correlated with deficient antithrombin III activity.

Induced hyperglycemia in normal subjects increases alpha 2-macroglobulin (alpha 2M) activity and alpha 2M concentration and reduces antithrombin III (ATIII) activity, while it does not affect ATIII plasma concentration. Hyperglycemia-determined variations in ATIII activity and alpha 2M molecules are correlated in an inverse and parallel fashion. A compensatory role for the increase in alpha 2M in the regulation of the coagulation system may be hypothesized. Moreover, these data provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may influence the levels of some risk factors for the development of complications in diabetes.

Adult↗

PubMed1989

Structure-activity relationships in 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives.

New 4-deoxyhalogenopyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives (V-VIII) have been prepared as an extention of a program which led to the synthesis of analogous pyrido- and alkylpyrido compounds (I-IV) displaying a low level of g.i. absorption. The new compounds give comparatively much lower ED50 p.o./s.c. ratios showing a recovery in the extent of oral absorption. XPS, N.M.R., and HPLC data rationalize this activity in hydrophilicity due to the electron-withdrawing inductive effect of the halogen atoms bound to the pyridoimidazo system. This effect is exerted in particular on the negatively charged N(2'), and is the opposite as that exerted by the alkyl groups present in (I-III).

Bacteria↗

PubMed1989

Synthesis of 2-hydroxyacetyl-7-acetyl-xanthone, a new xanthone derivative endowed with antianaphylactic, analgesic, and antiinflammatory activities.

2-Hydroxyacetyl-7-acetylxanthone (V), a new xanthone derivative, was synthesized in four steps starting from xanthene, by two synthetic approaches. The new compound displayed antianaphylactic activity in the PCA test and in the anaphylaxis shock test in rats. It also displayed analgesic activity in the writhing test in mice, and antiinflammatory activity in the carrageenin edema test in rats. The activity of the new compound has been tentatively interpreted on the basis of its chemical and structural analogy with known drugs.

Anaphylaxis↗

PubMed1987

Sensitivity to rifaximin and rifampicin of Mycobacterium tuberculosis isolated from guinea pigs treated orally with rifaximin.

The in vitro sensitivity of the H 37 RV strain of Mycobacterium tuberculosis to rifaximin and rifampicin was determined by evaluating both the antimycobacterial activity of the two rifamycin derivatives after oral administration to infected guinea pigs and the influence of rifaximin on the susceptibility to rifampicin of the isolated strain from spleen, lungs and liver. The results showed that after oral treatment with rifaximin no changes regarding the sensitivity of the strain to rifaximin and rifampicin were seen.

Animals↗