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Biomedical subjects

L Fontana

Publications and source records attributed to L Fontana.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

Mortality from specific causes among silicotic subjects: a historical prospective study.

A historical mortality study was conducted among 520 silicotic subjects diagnosed at the Department of Occupational Health of the San Martino Hospital, Genoa, Italy, between 1961 and 1980. Vital status was ascertained as of 1 January 1982. Age-, sex- and calendar-year-adjusted standardized mortality ratios (SMRs) for specific causes were computed using Italian as well as Genoa County male population death rates. The study shows statistically significant increased mortality from all deaths (SMR = 2.92), all cancers (SMR = 2.38), respiratory tract cancers (SMR = 6.85), respiratory tract diseases (SMR = 13.63), and from 'other diseases' (SMR = 6.81). The excess mortality from respiratory tract diseases and from 'other diseases' are mainly attributable to silicosis and silicotuberculosis, respectively. These findings confirm the existence of a causal association between silicosis and increased mortality from both malignant and non-malignant respiratory tract diseases. The high mortality from respiratory tract cancers was still present even after adjustment for smoking.

Adult

[Thymopentin as adjuvant therapy in the hepatitis B vaccination of non- or hyporesponsive subjects].

The efficacy of thymopentin as adjuvant therapy was assessed in 13 people who did not respond to standard anti-hepatitis B vaccination with Pasteur HEVAC or Merck HV-VAX. Thymopentin (Sindtomodulina, Italfarmaco)--was given in doses of 50 mg 3 times a week for 3 consecutive weeks, a booster dose of the vaccine (40 mcg HB VAX injected into the deltoid muscle, or 10 mcg HEVAC subcutaneous) being given at the start of the second week. In 69.23% of the patients whose anamnesis revealed no immune deficiency, the Merrieux Multitest showed defective cell-mediated immunity. The adjuvant treatment produced an adequate immune response to the vaccine (anti ABc antibody titre 10 mU/ml) in 76.9% of cases and normalised cell-mediated immunity in 66.6% of those found to be hypoanergic at basal screening.

Adjuvants, Immunologic

Complement activation is associated with the presence of specific human immunodeficiency virus (HIV)-anti-HIV immune complexes in patients with acquired immunodeficiency syndrome-related complex or lymphoadenopathy syndrome.

The complement system was examined in a group of eight patients (six with lymphoadenopathy syndrome (LAS); two with acquired immunodeficiency syndrome (AIDS)-related complex (ARC], who were found to be human immunodeficiency virus (HIV)-positive, for the presence of specific HIV-anti-HIV complexes. A significant impairment of the classical and/or alternative pathway was found associated with the presence of cleavage fragments of C3 and/or B and a significant reduction in the complement factors studied. Ultracentrifugation fractions of serum samples obtained from one of the patients were assessed for the detection of specific HIV-anti-HIV (GP41-anti-GP41) complexes and were incubated with normal human serum to determine their complement activation capacity. A clear complement activation was found with the fraction in which a clear peak of HIV-anti-HIV (GP41-anti-GP41) immune complexes was present. The results demonstrate that specific immune complexes and complement activation are sometimes concomitantly present in patients with AIDS-related disease and that specific immune complexes may be one of the causal factors of the pathogenesis of complement activation in these patients. Possible consequences for the severe immune regulation with relevance to the dramatic failure in treating the virus effectively are discussed.

AIDS-Related Complex

Deficiency of lymphocyte lectin-dependent cytotoxicity in myelodysplastic syndromes.

We studied a group of patients with myelodysplastic syndromes (MDS) for surface markers and cytotoxic activities of peripheral blood mononuclear cells (PBMNC). The results indicate a significant increase in the total count of CD11b+, Leu7+ and CD16+ with a percent reduction in CD4+. A reduction in PHA-induced cellular cytotoxicity (PHA-ICC) and NK activity were found. A similar phenotype was found both in refractory anemia (RA) and (RA) with excess of blasts (RAEB/RAEB-t). However, the functional activities reached the normal level only in RA patients; while in RAEB/RAEB-t patients a significant reduction was detected in PHA-ICC and NK activity.

Aged

Natural killer activity from normal peripheral blood lymphocytes against a human T lymphotropic retrovirus type III (HTLV-III)-infected cell line.

An H9-HTLV-III-infected cell line was used as a target in a short-term (3-hr) Cr release assay to assess its sensitivity to lysis by peripheral blood lymphocytes (PBL) from normal donors. The single cell cytotoxicity assay (SCCA) on poly-L-lysine-coated coverslips was used to investigate further the mechanism of binding and killing. Uninfected H9 and K562 cell lines were studied as controls. Our results argue in favour of a natural killer (NK) mechanism being operative on an H9-HTLV-III-infected cell line owing to the following findings: (1) the cell line is sensitive to lysis in a short-term assay; (2) its sensitivity is significantly higher than K562; and (3) the kinetics of lysis, as assessed by SCCA, is similar to that of K562, with a more efficient killing being detectable against H9-HTLV-III. Furthermore, a phenotypic analysis of effector cells suggests that CD4+ lymphocytes are also involved in the lysis of this target. Our data provide evidence for an immune mechanism that may be operative in HTLV-III infection. We then studied, by this method, five groups of patients: one (n = 20) affected by acquired immunodeficiency syndrome (AIDS), one (n = 20) by AIDS-related complex (ARC), one (n = 20) by lymphadenopathy syndrome (LAS), one group (n = 40) of HTLV-III seropositive, apparently healthy people, and one (n = 40) of healthy HTLV-III seronegatives.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex

Surface markers and cytotoxic activities of lymphocytes in monoclonal gammopathy of undetermined significance and untreated multiple myeloma. Increased phytohemagglutinin-induced cellular cytotoxicity and inverted helper/suppressor cell ratio are features common to both diseases.

To determine whether monoclonal gammopathy of undetermined significance (MGUS) resembles multiple myeloma (MM) with regard to phenotype and functional activity, 16 patients with MGUS and 16 with untreated MM were studied for surface markers and cytotoxic activities phytohemagglutinin-induced cellular cytotoxicity (PHA-ICC), antibody-dependent cellular cytotoxicity, natural killer (NK) activity. Our data showed a consistent immunological similarity between the two diseases. An increase in OKT8+ cells was evident in both patient groups and a significant reduction in the T4/T8 ratio, more pronounced in MM, was observed. Alterations in NK activity or ADCC were not found in MGUS or MM. A significant increase in PHA-ICC was demonstrated in the two diseases. The increase in PHA-ICC observed seems to be attributable to an increased frequency and/or lytic efficiency of PHA-ICC lymphoid effector cells. These data suggest that similar immunological alterations are common to the two diseases. The greater helper/suppressor ratio reduction observed in MM seems to be related to the more severe clonal proliferation in these patients.

Antibody-Dependent Cell Cytotoxicity

Modulation of human concanavalin A-induced lymphocyte proliferative response by physiological concentrations of beta-endorphin.

The effects of physiological concentrations of beta-endorphin on the proliferative response to concanavalin A of human peripheral blood mononuclear cells from a large series of healthy donors are reported. These effects are also compared with those obtained employing beta-endorphin and phytohemagglutinin under the same experimental conditions. The donors (32), aged between 20 and 48 years, chosen among military personnel of the Italian Air Force, underwent clinical and laboratory investigations to exclude any detectable disturbance in their psychophysical fitness. Our results show that beta-endorphin is not mitogenic per se and is unable to modify the response of mononuclear cells to phytohemagglutinin irrespective of the concentration of opioid or mitogen used. beta-Endorphin is also unable to alter the PBMC response to low concentrations of concanavalin A, but significantly increases such a response when higher concentrations of concanavalin A and concentrations of beta-endorphin similar to those found in human plasma under physiological conditions are used. The effect is not reverted by naloxone, the specific opiate antagonist. When the activity of beta-endorphin on the mononuclear cell response to concanavalin A is examined at the single donor level, it is noted that some of the donors fail to show the opioid-dependent increase. The baseline levels of the response to concanavalin A of such subjects, compared to those of the donors whose response is augmented by the opioid, are significantly higher, thus demonstrating that beta-endorphin can selectively modulate concanavalin A-induced mitogenesis with a behavior depending on the individual characteristics of the donor's response. The process involves non-opioid cell receptors.

Adult

A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction.

In a double-blind clinical trial, vinpocetine, a synthetic ethyl ester of apovincamine, was shown to effect significant improvement in elderly patients with chronic cerebral dysfunction. Forty-two patients received 10 mg vinpocetine three times a day (tid) for 30 days, then 5 mg tid for 60 days. Matching placebo tablets were given to another 42 patients for the 90 day trial period. Patients on vinpocetine scored consistently better in all evaluations of the effectiveness of treatment including measurements on the Clinical Global Impression (CGI) scale, the Sandoz Clinical Assessment-Geriatric (SCAG) scale, and the Mini-Mental Status Questionnaire (MMSQ). There were no serious side effects related to the treatment drug.

Aged