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Biomedical subjects

A Zambon

Publications and source records attributed to A Zambon.

68 records · Page 4Linked to original sources
PubMed1993

Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.

Hepatic triglyceride lipase (HL) is thought to play a role in the formation of low density lipoproteins (LDLs) from small very low density lipoproteins (VLDLs) and intermediate density lipoproteins (IDLs). To analyze the possible physiological role of HL in determining LDL buoyancy, size, and chemical composition, HL activity and LDL were studied in 21 patients with coronary artery disease (CAD) and 23 normolipidemic subjects. In both groups, LDL buoyancy and size were inversely associated with HL activity levels. The effect of HL on LDL size was comparable in CAD patients and in normolipidemic subjects. HL appeared to influence LDL lipid composition primarily by affecting the surface lipid components. The free cholesterol content of LDL particles was highly correlated with HL activity in both CAD and normolipidemic individuals. The free cholesterol to phospholipid ratio in LDL particles correlated with HL in both CAD and normolipidemic subjects. When the individuals were separated according to their LDL subclass patterns, pattern B subjects had significantly higher HL than pattern A subjects in both CAD and normolipidemic groups. The analysis of the cholesterol distribution profiles across the lipoprotein density gradient confirmed that LDL buoyancy is affected by HL. These data support the hypothesis that HL modulates the physical and compositional properties of LDL and contributes to the expression of the LDL subclass phenotype, suggesting a physiological role for HL in LDL metabolism.

Adult↗
PubMed1993

Plasma triglyceride and LDL heterogeneity in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a genetic disorder characterized by increases in plasma cholesterol and/or triglyceride, elevated apolipoprotein B, and heterogeneous low density lipoprotein (LDL). To examine the relation between plasma triglyceride concentrations and LDL heterogeneity, 13 hypertriglyceridemic FCHL patients with a predominance of small LDL (LDL subclass phenotype B) were treated with gemfibrozil. The distribution of LDL was determined using nondenaturing gradient gel electrophoresis and nonequilibrium density gradient ultracentrifugation. Mean plasma triglyceride levels decreased 55% (p < 0.01) after 3 months of treatment. Mean LDL peak particle size remained small (247 +/- 4 versus 249 +/- 5 A), and the correlation between change in plasma triglyceride concentrations and a change in LDL peak particle size was not significant. Individual changes in LDL flotation rate (Rf) were, however, inversely correlated with changes in triglyceride concentration (R = 0.60, p < 0.05). Although mean LDL Rf increased during treatment (p < 0.005) due to an increase in buoyant LDL, dense LDL remained elevated compared with that of a control population. Thus in FCHL patients, small, dense LDL persists despite decreases in plasma triglyceride concentrations.

Adult↗
PubMed1993

Lipoprotein abnormalities in well-treated type II diabetic patients.

OBJECTIVE: To investigate lipoprotein levels and composition in well-treated type II diabetic patients. RESEARCH DESIGN AND METHODS: Cholesterol and triglyceride levels were measured in plasma, VLDL, LDL, and HDL in 120 type II diabetic patients in good to fair metabolic control (HbA1c, 7.2 +/- 1.6%) and in 30 normal control subjects. ApoAI, AII, B, CII, CIII, and E levels in plasma were also determined. RESULTS: The diabetic patients have significantly higher levels of mean plasma cholesterol (5.85 vs. 5.43 mM, P = 0.03), LDL triglycerides (0.41 vs. 0.31 mM, P = 0.003), and HDL triglycerides (0.24 vs. 0.19 mM, P = 0.02), whereas total triglycerides, VLDL cholesterol and triglycerides, LDL cholesterol, and HDL cholesterol are not significantly different from normal control subjects. ApoB (150 vs. 135 mg/dl, P = 0.02) and apoCIII (10.6 vs. 8.4 mg/dl, P = 0.01) are significantly higher in diabetic patients compared with control subjects. No significant differences are observed in all the parameters among diabetic patients treated with diet only, sulphonylurea, sulphonylurea plus biguanides, or insulin. Body weight is significantly related to VLDL lipids. The VLDL triglycerides are inversely related to the HDL cholesterol in both diabetic patients and control subjects. The VLDL triglycerides are directly related to the HDL triglycerides only in diabetic patients. No other lipid or lipoprotein parameters are significantly related to body weight or metabolic control. CONCLUSIONS: Type II diabetic patients in good to fair metabolic control are characterized by minor alterations of the plasma lipids, but LDL and HDL triglycerides, apoB, and apoCIII are increased, thus indicating that the lipoprotein composition is altered, possibly because of an abnormal triglyceride metabolism and/or lipid transfer activity.

Aged↗
PubMed1993

Analysis of techniques to obtain plasma for measurement of levels of free fatty acids.

Accuracy in measurement of plasma free fatty acids (FFA), and therefore prevention of the in vitro lipolysis, is a crucial step to understand the physiologic role of plasma FFA and their relationships in the pathogenesis of important metabolic disorders such as central obesity, insulin resistance, and diabetes mellitus. As lipoprotein triglyceride-fatty acids are elevated in these states, in vitro lipolysis of triglycerides may artifactually increase FFA. Plasma FFA were measured in subjects before and after heparin administration, under different experimental conditions affecting the in vitro activity of lipoprotein lipase (LPL) and hepatic lipase (HL). Paraoxon, a cholinesterase inhibitor neurotoxin known to block plasma lipolytic activity, and preextraction timing and temperature of collection were tested. Paraoxon was required to prevent triglyceride hydrolysis in: a) preheparin plasma allowed to stand at room temperature (21 degrees C) for 2 h, before being frozen at -20 degrees C (FFA = 1817 +/- 291 vs. 698 +/- 66 microEq/l, P < 0.005, mean +/- SEM, without and with paraoxon, respectively); and b) in postheparin plasma immediately stored at -20 degrees C (FFA = 2682 +/- 357 vs. 1299 +/- 150 microEq/l, P < 0.005, without and with paraoxon, respectively). No difference in the FFA level was found in preheparin plasma collected either with or without paraoxon when: a) the samples were placed in ice and immediately assayed; b) the specimens were immediately frozen at -70 degrees C and assayed 60 days later.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1992

Role of P2z purinergic receptors in ATP-mediated killing of tumor necrosis factor (TNF)-sensitive and TNF-resistant L929 fibroblasts.

Two closely related cell lines were characterized in their responses to extracellular ATP (ATPo): the fibroblast cell line L929 and a TNF-resistant variant L929/R. Both lines showed ATPo-activated increases in intracellular Ca2+, inward current, and sustained depolarization of the plasma membrane, cell responses compatible with activation of purinergic receptors of the P2y, P2x, or P2z subtype; however, only the L929/R variant was susceptible to ATPo-dependent early permeabilization of the plasma membrane to hydrophilic solutes of M(r) below 900, a response uniquely caused by the activation of P2z receptors. Both cell types were susceptible to the cytotoxic effect of ATPo, but killing of the L929/R variant required much shorter incubations in the presence of this nucleotide. Morphologic examination of ATPo-challenged L929 and L929/R cells showed that cell death occurred by two alternative mechanisms: colloido-osmotic lysis or apoptosis. Occurrence of apoptosis was confirmed by agarose gel analysis of cellular DNA. Although ATPo caused a fast mobilization of intracellular Ca2+, neither colloido-osmotic lysis nor apoptosis were Ca2+ dependent. Our results show that the L929/R variant, but not the L929 parental fibroblast cell line, expresses functional purinergic receptors of the P2z subtype. The presence of P2z receptors confers to L929/R cells enhanced susceptibility to ATPo-mediated cytotoxicity.

Adenosine Triphosphate↗
PubMed1992

Lipoprotein sub-fraction levels and composition in obese subjects before and after gastroplasty.

Obesity is frequently associated with several alterations of plasma lipid levels and lipoprotein metabolism. To evaluate the effects of severe obesity and weight loss on plasma lipoprotein sub-class levels and composition 11 grossly obese patients were examined before and six and 12 months after gastroplasty. Plasma lipoproteins were isolated by ultracentrifugation in a zonal rotor under rate flotation conditions. Mean body weight was 121.9 kg before gastroplasty, 97.6 kg after six months, and 90.7 kg after 12 months. Total plasma cholesterol was not affected by the weight reduction. Obese patients were characterized by increased levels of IDL and small dense LDL (LDL3). LDL levels, but not LDL3, were reduced following weight reduction. Plasma apo B levels of obese patients were always higher than in controls and were not affected by the weight reduction. After 12 month's weight loss total HDL cholesterol increased without modification of HDL sub-class cholesterol distribution, which was similar to that of normal controls. Plasma apo AI in obese patients was not affected by changes in body weight, and remained below normal. The percentage protein-lipid composition of LDL2 and HDL3 in obese patients was characterized by a decreased cholesterol ester content before gastroplasty which was normalized 12 months after gastroplasty. The presence of IDL and LDL3 in increased concentrations in severely obese patients may represent a vascular risk factor since similar abnormalities were recently observed in non-obese patients affected with vascular diseases.

Adult↗
PubMed1992

Role of adhesion molecules in the immune reaction to M-MSV-induced tumors.

We have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs.

Animals↗
PubMed1992

The in vivo role of leukocyte function-associated antigen-1 in cytotoxic cell activity against tumors induced by Moloney-murine sarcoma/leukemia retroviral complex.

The in vivo role of LFA-1 molecule in the immune reaction to a murine retrovirus-induced tumor was investigated. Local and systemic treatment with high doses of anti-LFA-1 monoclonal antibody led to tumor progression by blocking CTL interaction with tumor cells without interfering with CTL generation and localization in the tumor mass.

Animals↗
PubMed1985

Involvement of monoaminergic and peptidergic components in cathinone-induced analgesia.

Evidence has been obtained suggesting that cathinone-induced analgesia depends upon stimulation of alpha-adrenoceptors, followed by release of opioid peptides and by activation of serotonergic pathways. This hypothesis is supported by the following. (1) Cathinone potentiated morphine analgesia and the whole effect was antagonized by naloxone whereas onto the cathinone potentiation was counteracted by phenoxybenzamine. (2) Bestatin potentiated cathinone-induced analgesia and this effect was sensitive to both naloxone and phenoxybenzamine blockade. (3) The analgesic effect of cathinone + bestatin was further potentiated by the serotonin uptake inhibitor citalopram.

Alkaloids↗
PubMedDate not supplied

Outcome variables in the evaluation of alcoholics' treatment: lessons from the Italian Assessment of Alcoholism Treatment (ASSALT) Project.

The observational evaluation of alcoholics' treatments requires a combined analysis of alcoholic behaviour during treatment and of adherence to therapeutic programmes. The application of survival analysis techniques in this setting has been explored in this study. Two hundred and seventy alcoholics admitted to 15 Italian treatment units in a 1-year period were followed-up for 2 years, recording date and length of every recurrence episode and of definitive or transitory interruption of the planned treatment. An extensive use of several survival analysis techniques was made. The length of time between the start of the treatment and the first episode of relapse did not give a reliable measure of frequency of failures. Conversely, the length of time between the start of treatment and withdrawal appeared to be unbiased. The cumulative proportions of treatment-compliant patients (and the corresponding 95% confidence intervals) were 71% (66-76%), 63% (57-69%) and 53% (47-60%) after 6 months, 1 year and 2 years respectively from the start of treatment. Cumulative abstinence duration before withdrawal was significantly and positively associated with the risk of first, of definitive, and of every episode of treatment interruption. This first application of survival analysis techniques to the combined study of alcoholic behaviour and of adherence to treatment can improve our knowledge of treatment evaluation. Our results suggest that compliance to treatment is an objective and versatile outcome measure. Long-term follow-up studies aimed to elucidate the determinants of withdrawal should be performed.

Alcoholism↗
PubMedDate not supplied

Meta-analysis of alcohol intake in relation to risk of liver cirrhosis.

The heterogeneity in the results of observational studies that investigated the association between alcohol consumption and risk of liver cirrhosis was analysed by means of a meta-analysis that included 15 articles published from 1978 to 1997. Relative risks associated with low levels of alcohol intake (25 g/day) ranged from 1.5 [95% confidence interval (CI): 1.4-1.5] for a linear model fitting the results of the six studies performed in Mediterranean areas, to 3.6 (95% CI 3.1-4.3) for a quadratic model fitting the results of the nine studies performed in other areas. A strong indication of heterogeneity was observed when combining all studies. Quadratic term of alcohol intake, quality of the study and area in which the study was performed explained most of this heterogeneity. Efforts should be made to explain the strong heterogeneity in the trend estimates. Reproducible methods to collect relevant and valid information on alcohol intake should be developed and the role of drinking patterns and viral and nutritional factors in modifying the effect of alcohol on the risk of liver cirrhosis should be investigated.

Alcohol Drinking↗