Biomedical subjects

L Fontana

Publications and source records attributed to L Fontana.

At least 91 records · Page 5Linked to original sources

PubMed1995

Effects of 1,2-dichloroethane intoxication on dolichol levels and glycosyltransferase activities in rat liver microsomes and Golgi apparatus.

Rat intoxication with a single dose of 1,2-dichloroethane (DCE) (50 microliters/100 g b.w) is able to induce a significant modification of protein glycosylation in the liver endoplasmic reticulum and Golgi apparatus. HPLC analysis shows that within 5-60 min after DCE-intoxication, the levels of total dolichol, free dolichol and dolichyl phosphate strongly decreased in the microsomes and Golgi apparatus. Particularly in total microsomes, dolichyl phosphate, which is rate-limiting for the biosynthesis of the N-linked oligosaccharide chains, drops to values significantly lower than in the control group 15 min after DCE poisoning. In the Golgi apparatus, the total dolichol, essential to enhance the fluidity and permeability of these membranes, early and significantly decreases already 5 min after DCE poisoning. Moreover, in the Golgi apparatus galactosyl- and sialyltransferase activities, the main enzymatic activities of terminal protein glycosylation, are significantly reduced, as measured 15 min after DCE intoxication. These data suggest that the impairment of glycoprotein synthesis, maturation and secretion may be involved in the pathogenesis of liver injury induced by acute DCE-intoxication.

Alanine Transaminase↗

PubMed1995

Changes in fatty acid composition of plasma, liver microsomes, and erythrocytes in liver cirrhosis induced by oral intake of thioacetamide in rats.

The aim of this study was to evaluate the changes in fatty acid composition of lipids of plasma, erythrocytes, and liver microsomes in rats with liver cirrhosis induced by oral intake of thioacetamide and to determine to what extent the experimental model reproduces the fatty acid tissue alterations reported in human cirrhosis. Two groups of rats were studied. The control group received water ad libitum, and the experimental group received 0.03% w/v thioacetamide in drinking water for 2, 4, and 6 months. At these times, lipids of plasma, erythrocytes, and liver microsomes were extracted, and their fatty acid compositions were determined. Thioacetamide intake led to macronodular and micronodular cirrhosis at 2 months. These alterations progressed at 4 months and eventuated in liver tumors at 6 months. Thioacetamide-treated rats showed a drop in total plasma fatty acids, higher percentages of palmitic acid in all lipid fractions, and lower levels of stearic acid in erythrocyte lipids and liver microsomal phospholipids. Oleic acid increased in plasma cholesteryl esters and phospholipids, as well as in erythrocyte lipids and liver microsomal phospholipids. In plasma lipids and liver microsomal phospholipids, the percentages of arachidonic and docosahexaenoic acids decreased. The latter also decreased in erythrocyte lipids. In addition, liver microsomes showed a higher cholesterol/lipid phosphorus molar ratio. The experimental model of cirrhosis obtained by intake of thioacetamide in drinking water for 4 months reproduces many of the fatty acid tissue alterations that appear in human cirrhosis and may serve to ascertain the biochemical mechanisms involved in these changes.

Administration, Oral↗

PubMed1995

Oxidized LDL and reduction of the antiaggregating activity of nitric oxide derived from endothelial cells.

Oxidized LDL has been observed to induce abnormalities in endothelial function which may be relevant for the progression of atherosclerotic lesions. We studied in vitro the possible effects of oxidized LDL on the antiaggregating activity of endothelial cells, which is dependent on release of prostacyclin and nitric oxide. We used an experimental model in which cultured human endothelial cells were placed in the aggregometer in contact with human platelets, after blockade of cyclo-oxygenase by adding acetylsalicylic acid. In this way the antiaggregant effect of endothelial cells was dependent on the release of nitric oxide alone; prevention of antiaggregant activity by preincubation of endothelial cells with 300 microM L-NG-mono-methylarginine confirmed this. When this system was used, endothelial cells (2-7.5 x 10(5)/ml) almost completely inhibited thrombin-induced (0.02-0.08 U/ml) platelet aggregation (2 x 10(8) platelets/ml), measured according to Born (11.1% +/- 8.5 vs 68.6% +/- 12.6, M +/- SD). This antiaggregating activity was reduced when slightly oxidized LDL 100 micrograms/ml (35.2% +/- 14.9, p < 0.001), but not native LDL 100 micrograms/ml (7.5% +/- 7.6), was added immediately before aggregation was induced. Incubation of endothelial cells with oxidized LDL 100 micrograms/ml for 1 h did not affect the antiaggregating capacity, unless oxidized LDL was present during aggregation (18.3% +/- 10.2 vs 35.8% +/- 9.6, p < 0.02). No significant direct effect of either oxidized or native LDL on stimulated platelet aggregation was observed. Our results indicate that slightly oxidized LDL can reduce the antiaggregating properties of the endothelium, probably by interaction with NO rather than through inhibition of its synthesis.

Aspirin↗

PubMed1995

[Clinical and capillaroscopic study of Raynaud's phenomenon in retired patients previously exposed to vinyl chloride monomer].

UNLABELLED: The course of Raynaud's phenomenon (RP) after the end of exposure to vinyl chloride monomer (VCM) is not really well known. Fourty four subjects were studied, from 128 retired patients who were exposed to VCM (end of the exposure since 8 years at least): 17 complained of "white finger crisis", and 27 voluntary retired subject without complaints (table II). The aims of this study were to specify capillaroscopic and clinical characteristics of these complaints to define and to assess the role of VCM. Each patient underwent an interview, a clinical examination and a nailfold capillary microscopy examination. RESULTS: 1) The 17 pensioners with complaints suffered from RP. But for 12 of them the onset of RP was in the exposed period (table I). From the clinical interview, the clinical and capillaroscopic examinations in these 12 RP may be attributed to the past exposure to VCM. 2) The majority of 44 subjects showed no capillary abnormalities. For 3 subjects changes consisted in isolated capillary dystrophia (1 with PR, 2 without PR) and for 2 subjects changes consisted in isolated neocapillaries (1 with PR, 1 without PR). The other microvascular changes were not specific (table III). In conclusion, RP secondary to VCM can still persist after the end of exposure in patients who suffered from RP during the exposure, 9% of the population (12/128). In view of discordance of clinical symptoms and capillaroscopic abnormalities, capillary lesions did not appear as the main physiopathologic factor in the persistence of the PR secondary to CVM.

Capillaries↗

PubMed1995

Mortality among silicotics in Genoa, Italy, from 1961 to 1987.

A historical cohort mortality study conducted among 515 silicotic subjects revealed higher than expected risks for all causes [standardized mortality ratio (SMR) 1.89], respiratory tract diseases (SMR 8.89), silicotuberculosis (SMR 27.00), respiratory tract cancers (SMR 3.14), and lung cancer (SMR 3.50). Mortality from cardiovascular diseases was lower than that expected (SMR 0.51). Lung cancer risk increased with duration of occupational exposure (SMR 2.80, 2.99, and 5.02 for 14, 15-29, and 30 years of employment, respectively). Lung cancer risk was higher for the silicotics without tuberculosis (SMR 3.72) than for those with tuberculosis (SMR 2.83). Indirect adjustment for smoking habits, including number of cigarettes smoked per day, showed that smoking would have been responsible for a maximum risk of 1.77. Thus smoking may have explained 50% of the observed excess mortality from lung cancer.

Adult↗

PubMed1994

Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane.

BACKGROUND: 1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum. METHODS: Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. RESULTS: After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars). CONCLUSIONS: Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.

Animals↗

PubMed1993

Regulation of spermidine transport in L1210 cells.

1. 1 mM 2-amino isobutyric acid (AIB), glutamine or asparagine when preincubated for 3 hr with L1210 cells promoted a marked increase in the rate of spermidine uptake. 2. Cycloheximide also increased the transport rate and completely prevented the increase due to AIB. 3. Trifluoperazine and iso-H7 inhibited the uptake of spermidine, much less the uptake of AIB. 4. Adenosine promoted an increase in the uptake of AIB, a decrease in that of spermidine. 5. Hypotonic stress also increased the rate of spermidine transport. This modification was only partially prevented by cycloheximide. 6. Okadaic acid had no effect on this increase, whereas it prevented the increase of ODC activity.

Animals↗

PubMed1993

Complement activation and sensitizing antibodies in Lyme borreliosis. A microbial adherence immobilization assay for Borrelia burgdorferi (MAIA-BB).

A report is presented about the capability of complement to directly clump Borrelia burgdorferi. The new phenomenon which has been termed "microbial adherence", is either antibody-independent or requires the presence of "sensitizing" antibodies depending the strains tested. Microbial adherence is associated with immobilization and killing of borrelias. A microbial adherence immobilization assay for B. burgdorferi (MAIA-BB) was developed to detect sensitizing antibodies in patients with Lyme borreliosis and in B. burgdorferi-infected animals.

Animals↗

PubMed1993

[Changes in lipoglycoprotein metabolism in toxic fatty liver].

BACKGROUND: A number of agents that produce liver injury also cause the accumulation of an abnormal amount of fat, predominantly triglycerides (TGs) in the parenchymal cells. Fatty liver (FL) is the result of an hepatocyte imbalance between the rate of synthesis and output of TGs into the plasma. TGs are not secreted as such, but combined with a glycoprotein moiety, and particularly with the very low density lipoproteins (VLDLs). This fraction is involved in the transport of hepatic TGs to extrahepatic tissues. FL can be induced by either acute or chronic administration of ethanol (EtOH), and/or several haloalkanes (carbon tetrachloride, CCl4; 1.2-dichloroethane, DCE; 1.1.2.2-tetrachloroethane, TTCE), both in laboratory animals and in man. Since the pathogenesis of this disease is a crucial problem, as yet undefined, the purpose of this article is to summarize the studies which have unraveled some of the mechanisms involved in FL, particularly the role played by impaired lipoglycoproteins (LGP) metabolism in rat liver. DISCUSSION: An important element in the pathogenesis of EtOH- and haloalkanes-induced FL is the impairment of hepatic secretion of VLDLs, which occurs soon after poisoning. Various steps of the secretory pathway are probably involved in the expression of such damage. The intoxication of rats with these xenobiotics leads to an early impairment of the hepatocyte system responsible for terminal glycosylation and maturation of LGP at the level of three different subfractions (F1, F2 and F3) of purified Golgi apparatus (GA). The earliest functional change is a block of LGP transit through the GA cisternae and vesicles, both in isolated hepatocyte model and in the whole animal. The glycosylation of LGP is a multistep process which starts in the rough endoplasmic reticulum (RER), and comes to its end in the GA. Dolichols (Dol) are a family of long-chain polyisoprenoid alcohols, present either as neutral free-Dol and dolichyl-phosphate (Dol-P). The latter acts as a glycosyl carrier across the RER membranes in the initial steps of LGP biosynthesis. Nearly all the other reactions occur in GA, where free-Dol have a role either in terminal LGP processing or in their secretion into the blood stream. Several investigations indicated that both EtOH and haloalkanes (CCl4, DCE, and TTCE) may selectively and precociously impair the total microsomes (TM) and GA pool of Dol, particularly in F1. Lipid peroxidation appears to be the fundamental mechanism involved. CONCLUSIONS: Such results, obtained in several works, point out a key role played in FL by selective impairment of MT and GA processes which provide for the synthesis, maturation and release of hepatic LGP.

Animals↗

PubMed1992

Aluminum(III) influences the permeability of the blood-brain barrier to [14C]sucrose in rats.

To determine the influence of the metal coordination sphere on the permeability of the blood-brain barrier (BBB), rats were injected intraperitoneally with aluminum lactate (Al(lact)3), aluminum acetylacetonate (Al(acac)3), aluminum maltolate (Al(malt)3) at pH 7.5, or with physiological saline. Two h after each treatment, [14C]sucrose physiological saline solution was injected in animals, and the radioactivity was measured in 5 brain regions (cerebral cortex, mesencephalon, diencephalon, medulla-pons, cerebellum). Radioactivity was significantly elevated in brains from animals treated with Al(malt)3 (hydrolytically stable and hydrophilic), and with Al(acac)3 (hydrolytically stable and lipophilic) but not with Al(lact)3. Time-course study carried out at 2, 4 and 24 h with different aluminum compounds showed a persistent radioactivity 24 h after treatment only in the brain from animals treated with Al(acac)3. Morin stain localized AlIII only in neurons from animals treated with Al(acac)3. These findings indicate that AlIII alters the BBB function in the rat either permanently or transiently depending on the physiochemical properties of the metal coordination sphere. Implications of these results, in terms of AlIII as a potential toxic factor in humans, are considered and discussed.

Aluminum↗

PubMed1992

Ability of recombinant interferon gamma in vitro to restore the defective polymorphonuclear-cell- but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes.

In this study we analysed the in vitro effect of recombinant interferon gamma on cytotoxic activities mediated by both lymphoid and polymorphonuclear cells from 16 patients with myelodysplastic syndromes. Our results indicate the inability of interferon to restore the defective natural killer activity, natural killer cells and lectin-induced cytotoxicity. On the contrary we detected a boosting effect on the depressed polymorphonuclear cell cytotoxic activities. In our view, the ability of interferon to potentiate polymorphonuclear cell lytic efficiency could support an alternative defensive pathway against either neoplastic or infectious agents.

Aged↗

PubMed1992

Cystic ovaries in women affected with hereditary angioedema.

Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic-pituitary) abnormality, including high plasma beta-endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (HANE) during attacks as well as during symptom-free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HANE who were not on oral contraceptives. We have found PCO in 5/13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.

Adolescent↗

PubMed1992

Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma.

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed.

Complement Activation↗

PubMed1992

Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy.

A collaborative survey was carried out in Italy on a group of 59 subjects with a past history of meningococcal meningitis. The aim was to evaluate the prevalence of complement deficiencies, the serogroup of meningococci responsible for the disease and other possible immune abnormalities associated with the infection. Complement analysis allowed the detection of 10 cases (17%) with deficiencies of the terminal components, and in particular six cases of C8 beta, three of C7 and one of C6 defect. Half of the subjects with complement deficiencies had recurrences of meningitis and developed the infection at an older age in comparison with the control group with normal complement activity. The meningococcal C strain was the most diffuse (68%) and infected all the complement-deficient subjects. Evaluation of the antibody response to meningococcal capsular polysaccharides (PS) showed that only 42.5% of the individuals with group C had antibodies as opposed to 83% and 100% of the patients with meningitis due to group A and B, respectively. In all 59 subjects serum Ig as well as IgG subclasses were present, at normal levels for the age. Vaccination of seven out of the 24 subjects without detectable anti-meningococcal PS antibodies with the sole PS A+C induced a normal response in six of them, including a subject with complement defect. In the subject who did not respond to the antigen, the antibodies against the ubiquitous pneumococcal PS type 14 were also lacking, whereas anti-tetanus toxoid (TT) antibodies were normally present. From these data we may conclude the following: (1) the high prevalence (17%) of late complement components defect among survivors of meningococcal meningitis is also confirmed in the Italian population; (2) the serogroup C, responsible for the infections in all the cases with late complement components defect, is highly recirculating in Italy and apparently less immunogenic; (3) specific vaccination with meningococcal PS is a valid prophylaxis in subjects with lack of specific antibodies as well as in subjects with complement defect.

Adolescent↗

PubMed1991

A long-term toxicological investigation on the effect of tris(maltolate)aluminum(III) in rabbits.

The toxicity of i.v. injected hydrophilic aluminum complex tris(maltolate)aluminum(III) was studied in New Zealand white rabbits for a period of time ranging from 5 to 63 wk. Animals were injected 3-5 times a week with 1 mL of 7.5 mM Al(malt)3 and one rabbit with a dose 10 times higher after 14 wk of treatment. Autopical examination was performed on all animals. Chemoclinical analysis (glucose, urea, creatinine, cholesterol, bilirubin, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, LDH, CK, total protein, triglycerides, and Ca2+) gave no variation in treated animals with respect to the control. The toxicological data show a moderate systemic general toxicity at doses far higher than those used in similar previous experiments using Al(acac)3 (acac = 2,4 pentanedionate), a hydrolytically stable and more lipophilic aluminum(III) complex (1). The diversity of behavior is discussed in terms of metal speciation as well as respect to the thermodynamic and kinetic properties of the two complexes in aqueous solution. The toxicological model presented here emphasizes that neutral, water compatible aluminum(III) complexes are to be considered as promising tools for toxicological experiments providing biological models of human pathologies.

Aluminum↗

PubMed1991

Ultrastructural investigation demonstrating reduced cell adhesion on heparin-surface-modified intraocular lenses.

A major attention is focused at present to the surface characteristics of intraocular lenses (IOLs), which determine the biological response to the prostheses. There is now an overwhelming information on the fact that some cell types adhere to a lesser extent onto heparin-surface-modified (HSM) polymethylmethacrylate (PMMA) IOLs, either in vitro and in vivo. The present work aimed at sheding new insights by applying ultrastructural techniques of analysis. Our results basically confirm that human fibroblasts, platelets and monocytes are less in number when cultured onto HSM PMMA IOLs as compared to untreated PMMA IOLs. In addition: (1) the submicroscopic morphology of the cells cultured onto HSM PMMA IOLs appears to be normal, thus confirming the noncytotoxicity of the material; (2) fibroblasts grown onto PMMA IOLs are confluent and multilayered; they appear to be in a state of intense activity; the cytoskeletal elements are regularly arranged, and several points of contact at the interface are found; the rare cells present on HSM IOLs do not show at all any of these features; (3) the basic forms of resting and activated platelets are seen onto PMMA IOLs while no sign of activation is observed onto HSM IOLs, and (4) the ultrastructural morphology of monocytes does not differ significantly between the different IOLs. However, other studies are still in progress in order to localize and quantitate the specific receptors responsible for the eventual activation of these cells.

Blood Platelets↗

PubMed1991

"Working for Patients": the National Health Service in the 1990s.

The National Health Service in England is on the verge of sweeping changes that would apply free-market methods to the state-financed health care system. The government proposal, WORKING FOR PATIENTS, would bring about the most far-reaching changes in the NHS since it was founded following World War II. This paper examines a number of important issues and questions raised by the White Paper on the NHS. One cannot understand the proposed changes in the NHS in abstraction from the broader context of the basic principles upon which the NHS was originally established: universalism, equality, accessibility, and continuity of care. The so-called reforms contained in the White Paper potentially threaten an internationally unique national health care system.

Economic Competition↗

PubMed1990

Complement, complement activation and anaphylatoxins in human ovarian follicular fluid.

Functionally active complement was sought and detected in human follicular fluids obtained during the pre-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity and alternative pathway activity were present in nine fluids from four different donors with values within the normal serum range. The immunochemical analysis demonstrated the presence of complement factors from C1 to C9, of B and of C1 INH, H, I. Complement anaphylatoxins were found employing RIA techniques in amounts significantly higher than in human plasma, thus demonstrating that follicular fluid complement, at least during the pre-ovulatory period, is partially activated. A possible role for urokinase-like substances in such an activation was indicated by further in vitro experiments. The presence of active complement in follicular fluid can be relevant for the function of the enzymatic multi-factorial mechanism of ovulation.

Anaphylatoxins↗