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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 271 records · Page 15Linked to original sources
PubMed1988

Depression of liver drug metabolism and increase in plasma fibrinogen by interleukin 1 and tumor necrosis factor: a comparison with lymphotoxin and interferon.

Different recombinant cytokines were studied for their effects on mouse liver in vivo: interleukin 1-alpha and -beta, tumor necrosis factor, lymphotoxin, interferon-alpha A/D and gamma depressed liver cytochrome P450-dependent drug metabolism (measured by ethoxycoumarin deethylase activity) 24 h after treatment, at doses in the microgram range, while IL-2 had no effect on this enzymatic system. Interleukin 1 (both alpha and beta), tumor necrosis factor and lymphotoxin also increased plasma fibrinogen, a marker of liver acute phase inflammatory response. Interferon-gamma and tumor necrosis factor had an additive effect in depressing liver drug metabolism. When tested in vitro on isolated hepatocytes, only interleukin 1 depressed P450-dependent drug metabolism, while all the other cytokines were inactive, thus suggesting that their effect on the liver in vivo is not a direct effect but is mediated by other mediators.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

Circulating immune complexes in serum and in cerebrospinal fluid of patients with multiple sclerosis. Characterization and correlation with the clinical course.

We studied circulating immune complexes (IC) in the serum and cerebrospinal fluid (CSF) of patients with clinically defined multiple sclerosis (MS), in order to establish a correlation with the clinical course of the disease and to investigate the molecular composition of the IC isolated from patients in active phase of the disease. Serum IC levels were found to be significantly increased in patients from the progressive and active relapsing-remittent subgroups with both the CIC-conglutinin and C1q-binding methods. High levels of IC in CSF were detected only in the subgroup consisting of the relapsing-remittent patients in disease exacerbation when IC were determined by the C1q-binding test. No significant increase in serum or in CSF were found using the mRF-I test. The preliminary results of a qualitative investigation on serum IC in MS indicated that they are heterogeneous in nature, their size is mainly of the intermediate type, and they contain IgG, IgM, complement components and beta 2-microglobulins, the latter presenting an observation both new and interesting for studies on serum IC in MS patients.

Adolescent↗
PubMed1988

Plasma opioids in alcoholics after acute alcohol consumption and withdrawal.

Beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) plasma concentrations were examined in ten chronic alcohol abusers, eight men and two women aged 25-56 years with histories of continuously elevated ethanol consumption dating from 5-30 years. Plasma levels of the two peptides were measured after acute alcohol consumption and then after 3, 6 and 9 days of forced abstinence, during chlordiazepoxide treatment. Beta-EP and beta-LPH concentrations were normal on all four occasions. A reduced sensitivity of opioid receptors to acute alcohol administration due to chronic alcohol consumption is suggested.

Adult↗
PubMed1988

Dopamine-depleting activity of L-3,4-(dioxyphenylacetyl)-phenylalanine.

Dioxyphenylacetyl-L-DOPA was synthesized and shown to be resistant toward oxidative cyclization in the presence of plasma and brain extracts. This new DOPA derivative is slightly inhibitory towards monoamine oxidase (IC50 2.5 mM) and the synaptosomal uptake of dopamine (IC50 0.35 mM) and acts as an antagonist of haloperidol (IC50 0.6 microM) in displacing 3H-spiroperidol from isolated dopamine receptors. The substance, although more hydrophobic than DOPA, overcomes the blood-brain barrier to a lower extent than DOPA and lowers the levels of dopamine and norepinephrine in the left and right hemisphere of mice treated with it for 10 days at a dose of 10 mg/kg/day. Dioxyphenylacetyl-L-DOPA inhibits red cell hypotonic hemolysis and brain Na/K+-ATPase activity in vitro and potentiates the barbiturate-induced sleep.

Animals↗
PubMed1988

Effect of chronic morphine on plasma and brain beta endorphin and methionine enkephalin in pregnant rats and in their fetuses or newborn.

Normal or pregnant rats were treated orally for 21 days or throughout pregnancy with water or increasing doses of morphine and killed on days 7, 14, and 21 of pregnancy and 1 day post partum. At these time intervals, plasma, pituitary, and hypothalamic concentrations of beta-endorphin and methionine enkephalin were measured in normal and pregnant rats. Moreover, pituitary and hypothalamic concentrations of the two peptides were also measured in fetuses and newborn. Plasma beta-endorphin and methionine enkephalin increased significantly during pregnancy without any specific effect of morphine. Pituitary concentrations of beta-endorphin were not modified either by pregnancy or morphine treatment, while methionine enkephalin concentrations increased on days 7 and 11 of pregnancy, in both water- and morphine-treated rats. The pattern of the two peptides in the hypothalamus is completely superimposable to the one present in the pituitary with the exception of an increase of beta-endorphin on day 21 of pregnancy, which is more evident in control animals. Consistently with our observations in human newborn and the neurological dysfunctions we observed in them, the concentrations of both the peptides are significantly increased in the hypothalamus of fetuses and newborn of morphine-treated mothers, while in the pituitary only beta-endorphin concentrations are increased.

Animals↗
PubMed1988

Prognosis and therapy of early acute idiopathic auditory failure.

The prognostic value of some otovestibular parameters was evaluated in 46 cases of acute idiopathic hypoacusis (AIH) and 12 cases of acute idiopathic anacusis (AIA) observed within 7 days of the onset. Recovery in AIH is predicted by some otoneurological parameters as mean pure-tone hearing threshold (PTA) for 500, 1,000 and 2,000 Hz, stapedial reflex and severe vertigo. None of these measures alone seems to have prognostic value. The expected recovery rate also is reflected in the various parameters taken as a whole. Subjects with mean PTA better than 70 dB HL together with stapedius reflex present for 500 and 1,000 Hz, no decay and no vertigo have a very favourable prognosis: 86% had complete or good recovery. On the contrary, subjects with mean PTA worse than 70 dB HL and with pathological stapedius reflex have a generally unfavourable prognosis: 35% had complete or good recovery. Vertigo as a symptom does not seem in itself to have an unfavourable prognostic value. Actually, patients with severe vertigo generally have a poor recovery. Vertigo as a symptom indeed is frequently associated with a more severe sensorineural lesion. Carbogen or heparin-dextran are not an effective treatment: complete-good global recoveries obtained in AIH without any treatment, with carbogen or with heparin-dextran were, respectively, 65, 68 and 62%. As a consequence, an early therapy with these substances has no apparent value. Patients affected with AIA have a very unfavourable prognosis. All of our patients with AIA had poor recovery. For the moment we feel it is easier to reach a satisfactory prognosis rather than to institute an effective or causal therapy in acute idiopathic auditory failure.

Adolescent↗
PubMed1988

Recombinant tumor necrosis factor reduces hepatic drug metabolism in vivo in the rat.

To verify the potential in vivo inhibitory effect on liver function of tumor necrosis factor (TNF), also known as cachectin, antipyrine and diazepam were chosen to probe the hepatic mixed-function oxidase system. A single dose of TNF (30 micrograms/kg) to rats significantly reduced the plasma clearance of antipyrine and diazepam by about 30% and 25%, respectively; this resulted in concomitant prolongation of the elimination half-life (t1/2) of the two drugs, although of borderline significance for the benzodiazepine. This was probably due to a decrease in hepatic cytochrome P-450 activities that are responsible for antipyrine and diazepam metabolism in TNF-treated rats. This could be of clinical relevance if a similar effect occurs in humans after therapeutically effective doses of this biological response modifier.

Animals↗
PubMed1987

Brain and spinal cord neuropeptides in adjuvant induced arthritis in rats.

The concentrations of brain and spinal cord beta-endorphin, met-enkephalin, dynorphin and substance P were measured in rats bearing the Freund adjuvant induced arthritis. Beta-endorphin brain concentrations decreased gradually in time with a nadir on day twenty-one, when arthritis was at its maximum, and were back to normal by day thirty-five, when arthritis was no more evident. Met-enkephalin concentrations increased in brain areas and in the lumbar spinal cord and returned to normal with the same time pattern, while dynorphin and substance P concentrations did not change. These data indicate that peripheral lesions can induce important changes in brain concentrations of some opioid peptides involved in the modulation of pain.

Animals↗
PubMed1987

Effect of a cholecystokinin antagonist on some effects of diazepam.

Dose responses were evaluated for the effects of diazepam alone or together with the cholecystokinin receptor antagonist CR 1409 on pentetrazole-induced convulsions, motor performance and spontaneous motor activity. The results obtained showed that the cholecytokinin antagonist potentiated the effects of diazepam on motor performance and the anticonvulsant activity of diazepam, while it did not affect spontaneous motor activity. The data presented are consistent with a role for cholecystokinin in some effects of diazepam.

Animals↗
PubMed1987

Autotomy and central nervous system neuropeptides after section of the sciatic nerve in rats of different strains.

Autotomy and the concentrations of beta-endorphin and Met-enkephalin in brain areas and the spinal cord were measured in Sprague Dawley, Wistar and Wistar Lewis rats thirty-five days after the section of one sciatic nerve. As expected, autotomy developed in Sprague Dawley and Wistar, but not in Wistar Lewis rats. In the Wistar Lewis, brain and spinal cord concentrations of Met-enkephalin increased, beta-endorphin concentrations were unchanged. In Wistar and Sprague Dawley rats the increase of Met-enkephalin was accompanied by a decrease of beta-endorphin. Administration of chlomipramine, a drug usually employed in the treatment of deafferentiation pain, normalized the concentrations of beta-endorphin in the Sprague Dawley and Wistar rats, and avoided the development of autotomy, while Met-enkephalin concentrations did never change. The data presented suggest a possible correlation between beta-endorphin and autotomy.

Animals↗
PubMed1987

Metabolism of caffeine to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil in the isolated, perfused liver from control or phenobarbital-, beta-naphthoflavone- and 3-methylcholanthrene-pretreated rats.

Caffeine metabolism to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was studied in the isolated, perfused rat liver. The [2-14C]-labelled drug and metabolites were separated by thin-layer chromatography or high-pressure liquid chromatography. The chemical structure of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was confirmed by mass spectrometry and it was quantitatively determined by liquid scintillation counting. 6-Amino-5-[N-methylformylamino]-1,3-dimethyluracil is one of the major metabolites of caffeine found in the perfusion medium. The kinetics of caffeine elimination and of the uracil metabolite formation were studied up to 2 h perfusion time using livers from control rats and rats pretreated with phenobarbital, beta-naphthoflavone or 3-methylcholanthrene. Phenobarbital pretreatment did not modify the rate of caffeine elimination or the extent of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil formation. In contrast, there was a highly significant inducing effect on both drug elimination and formation of the uracil metabolite in perfusions of livers from beta-naphthoflavone- and 3-methylcholanthrene-pretreated animals.

Animals↗
PubMed1987

Analysis of serum immune complexes isolated from patients with essential mixed cryoglobulinemia.

The analysis of the molecular composition of serum immune complexes (IC) in autoimmune diseases has assumed growing importance in the evaluation of their clinical significance and possible pathogenetic role. Essential Mixed Cryoglobulinemia (EMC) is typically a disorder characterized by the presence of high levels of IC with pathogenic action, by reduced serum complement levels and by an antiglobulin activity of the cryoprecipitable IgM. In this report we refer on the preliminary results of a study on the molecular composition of the cryoprecipitable IC isolated from the serum of five patients with EMC. The methodology we adopted involves the solubilization at 37 degrees C of the washed cryoprecipitates and the purification of the IgG-containing IC by affinity chromatography through a Protein A-Sepharose CL4B column. The analysis of the molecular component was carried out by electrophoresis in polyacrylamide gel containing sodium-dodecyl-sulphate (SDS-PAGE) followed by Immun-Blot. Our results, although very preliminary, suggest that this kind of study appears really suitable for the detection of specific antibody or antigenic components in the IC molecules involved in the etiopathogenesis of essential mixed cryoglobulinemia.

Antigen-Antibody Complex↗
PubMed1987

Detection, by an enzyme linked immunoadsorbant assay (ELISA), of IgM, IgG and IgA rheumatoid factors in patients with essential mixed cryoglobulinemia.

In order to investigate on some yet unclear aspects of the relationship between Rheumatoid Factor (RF) activity, cryoprecipitation and clinical features of Essential Mixed Cryoglobulinemia (EMC), we determined, by an ELISA technique, the IgM, IgG and IgA RF in 16 patients with EMC, 16 patients affected with seropositive Rheumatoid Arthritis (AR), taken as a reference, and 16 young, normal controls. For IgM RF a high rate of incidence of positive samples (11/16 = 69%) from the EMC group was found, with mean values significantly higher than controls (p less than 0.001) and quite similar to those of the RA group. The ELISA assay was performed at room temperature (RT) and at 37 degrees C, and only a slight increase of adsorbance values in the latter condition was observed. On the contrary, temperature revealed to be a critical experimental condition for the detection of IgG RF. In fact at 37 degrees C the mean values of EMC patients were similar to those of RA and control groups, while at RT a marked increase of adsorbance values was observed, in spite of the inactivation of IgMRF due to the preliminary pepsin digestion of the samples. More interesting are our results concerning IgA RF. In fact a high incidence of overnormal values (9/16 = 56.2%) were found in the EMC group, similar to those of RA patients, with mean values which significantly differ from the normal subjects (p less than 0.01). No relevant differences derived from the temperature at which the test was carried out. The relationship between IgA RF and clinical course of EMC seems to be a very stimulating aim for further investigations.

Arthritis, Rheumatoid↗