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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 253 records · Page 14Linked to original sources
PubMed1989

Some effects of fructose-1,6-diphosphate on rat myocardial tissue related to a membrane-stabilizing action.

This study aims at elucidating the mechanism of action of extracellular fructose-1,6-diphosphate (FDP). FDP is able to inhibit Ca++ entry into the myocardial tissue with an IC50 value of 11.5 mM and in addition, it is bound by rat heart slices, the binding being activated by Zn and conditions of chemical hypoxia induced by KCN and iodoacetate. The overall effect of extracellular FDP includes an increase of frequency and amplitude of contraction of perfused heart at concentration below 1 mM, and, in general, a stimulation of the oxygen consumption of the tissue. The antihaemolytic effect of FDP suggests its action as a membrane stabilizer. The effects of extracellular FDP on the myocardial cell can be interpreted both on the basis of a limited permeability of the cell membrane to it and as a purely extracellular effect transduced through the cell membrane with a final response consisting of an increase in the intracellular FDP.

Animals↗
PubMed1989

Synthesis and some properties of a homologous series of beta-carboline-3-carboxylic esters.

A homologous series of esters of beta-carboline-3-carboxylic acid was prepared by a new synthetic procedure. The first members of the series are convulsant or pro-convulsant agents while those with acyl residues longer than C4 show anticonvulsant activity. The affinity of the members of the series for the benzodiazepine receptor from rat brain decreases with the increasing chain length of the esters. The pentyl ester was studied in particular for its anti-convulsant effect on rats and mice treated with cardiazol. The compound also acts as a membrane stabilizer by inhibiting red cell hypotonic hemolysis and rat brain Na/K ATPase; its LD50 value is 12.5 mg/Kg and of particular interest is its lack of inhibitory effect on memory retention in mice at doses at which diazepam has inhibitory effects.

Animals↗
PubMed1989

Dexamethasone modulation of in vivo effects of endotoxin, tumor necrosis factor, and interleukin-1 on liver cytochrome P-450, plasma fibrinogen, and serum iron.

Treatment of mice with endotoxin (lipopolysaccharide, LPS) and the two LPS-induced monokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), caused a depression of liver cytochrome P-450 and related drug-metabolizing enzymes, as well as other acute-phase changes including increase in plasma fibrinogen levels and hypoferremia. However, only IL-1, not TNF or LPS, depressed cytochrome P-450 in cultured hepatocytes, suggesting that the effect of TNF in vivo might be mediated by a second mediator. TNF- or LPS-stimulated monocytes released a factor capable of depressing cytochrome P-450 in cultured hepatocytes. This factor was inhibited by anti-IL-1 antiserum, and its synthesis, like that of IL-1, was inhibited by dexamethasone (DEX). Pretreatment of mice with DEX protected against the depression of liver cytochrome P-450 by LPS or TNF but not by IL-1, suggesting that IL-1 directly depresses cytochrome P-450 and that DEX acts by inhibiting IL-1 synthesis in vivo induced by LPS or TNF. However, DEX did not inhibit two other effects of LPS and TNF in vivo: increase of plasma fibrinogen levels and decrease of plasma iron, suggesting that these might not be mediated by IL-1. Therefore, the effect of DEX in vivo, although supporting the hypothesis that depression of liver cytochrome P-450 by LPS and TNF is mediated by IL-1, indicates the existence of IL-1-independent pathways in the acute-phase response.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1989

Human red blood cell loading with hexokinase-inactivating antibodies. An in vitro model for enzyme deficiencies.

The primary cause of red cell destruction in enzymopathies of anaerobic remains controversial and difficult to investigate especially because the erythrocyte population in enzymopenic patients is largely heterogeneous. We have shown that loading human erythrocytes with monospecific enzyme-inactivating antibodies could be useful in understanding the biochemical modifications occurring in enzymopenic erythrocytes and the mechanisms leading to red cell destruction. Hexokinase-inactivating antibodies were prepared and loaded in human erythrocytes using a procedure of encapsulation based on hypotonic hemolysis, isotonic resealing and reannealing. Red blood cells loaded with anti-hexokinase IgG showed 20 +/- 3% residual hexokinase activity while all other enzymes were normal. Lactate production by these cells was 30% of controls while the amount of glucose metabolized in the hexose monophosphate pathway (HMP) was unchanged under resting conditions. However, in the presence of methylene blue HMP rates were only 12% of controls. Determination of adenine nucleotide levels suggests that the antihexokinase-loaded red blood cells are not able to maintain, in vitro, their ATP level as well as their 2,3-diphosphoglycerate. Osmotic fragility, methemoglobin, and reduced glutathione content were near normal. These and other properties of the antihexokinase-loaded erythrocytes were similar to those found in cases of hexokinase deficiency. When the antibody-loaded erythrocytes were chromatrographed on immobilized Protein A columns 66-70% of cells were retained by the column against 0-10% of controls suggesting that hexokinase inactivation promotes autologous IgG binding. Since the phenomenon is known to be associated with red cell phagocytosis, it could be concluded that in hexokinase deficiency red cells are mainly removed by phagocytosis, and that hemolysis probably occurs in cases of oxidative stress when the production of a large amount of reducing equivalents (NADPH) is needed but not provided by the hexokinase-deficient erythrocytes.

Animals↗
PubMed1989

2',3'-dideoxycytidine permeation of the human erythrocyte membrane.

The mechanism by which 2,3'-dideoxycytidine, an inhibitor of HIV-I infectivity, permeates the cell membrane was investigated. The influx of ddCyd into human erythrocytes was nonconcentrative. The initial velocity of both ddCyd influx and efflux was, in contrast to compounds that permeate the cell membrane via the nucleoside transporter, a linear function of nucleoside concentration in the 1 microM to 10 mM range and relatively insensitive to temperature. Furthermore, potent inhibitors of nucleoside transporter and other nucleosides were found to inhibit ddCyd influx only partially or not at all suggesting that ddCyd permeates the human erythrocyte membrane predominantly by nonfacilitated diffusion. This unusual characteristic seems to be due to the lack of 3'-hydroxyl moiety of ddCyd which appears to be an important determinant for the nucleoside carrier specificity rather than to lipid solubility itself. As far as permeation of the cell membrane is concerned ddCyd shares these properties with 2',3'-dideoxythymidine and 3'-azido-3'-deoxythymidine.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Fat cell size in various body region. A statistical analysis in Equus caballus.

In 13 horses from both sexes, between 5 months and 18 years of age, in good nutritional state, statistical evaluations of fat cell sizes were performed in 16 body regions. From direct and indirect measurements referred to the cell diameter and cell number in equivalent areas, carried out on sections from paraffin embedded material and on preparations of dissociated whole cells, it emerged that the adipose cells of the subserous fat of the abdominal floor are consistently the largest, whereas those of the orbital fat body and supraorbital fossa are the smallest. In the other regions the cells have intermediate sizes. Statistical elaboration of the data has shown that: 1) in every site the range of variation in cell size is very high; 2) in the same individual the limits of the range of variation in cell size between the fat deposits in different sites are the wider, the higher the mean cell size; 3) the limits of the range of variation in fat cell sizes between corresponding regions in different individuals are closely correlated with the mean cell size. The suggestion is advanced that in the sites with very variable cell sizes, lipids are more readily mobilized; but such hypothesis requires further substantiation.

Abdomen↗
PubMed1989

[Several properties of human red cells subjected to hypotonic dialysis and resealing to use them as vehicles for bioreactors].

The morphological and metabolic properties of red blood cells submitted to the procedure of loading by hypotonic hemolysis and isotonic resealing were compared with the controls. No appreciable differences could be detected concerning glycolytic ability, the amount of glucose metabolized in the hexose monophosphate pathway and the concentrations of glycolytic intermediates of ATP and of 2,3-DPG. Instead the concentration of reduced glutathione and the MCV were slightly reduced. These manipulated erythrocytes can be used as potential bioreactors or as carriers of exogenous substances.

Drug Carriers↗
PubMed1989

Improved stability of 2,3-bisphosphoglycerate during storage of hexokinase-overloaded erythrocytes.

Human red blood cells were overloaded with homogeneous human hexokinase using a procedure of encapsulation based on hypotonic hemolysis and isotonic resealing and reannealing to achieve a final activity that was 15 times higher than that in control cells. Storage for 5 weeks at 4 degrees C of hexokinase-overloaded erythrocytes shows that these cells undergo small K+ leakage and mean cell volume increase compared with control cells. Furthermore, after these 5 weeks of storage the 2,3-bisphosphoglycerate content was normal while the ATP concentration was slightly reduced. These results and other properties suggest that encapsulation of key glycolytic enzymes in erythrocytes can provide a new way to maintain in vitro functionally active red blood cells for at least 5 weeks.

2,3-Diphosphoglycerate↗
PubMed1989

[Treatment of dry skin by the use of a "physiologic" bath oil].

The results obtained by using a bath oil (Idrovel bath) for treating skin dryness, both primary and associated with pathological conditions, are reported. Twenty patients out of 40 considered for treatment were undergoing photochemotherapy. The patients were evaluated both subjectively and, in order to obtain an objective measuring of skin hydratation, by instrumental capacitance method. The results were very encouraging, characterized by a statistically significant increase of capacitance data after treatment. These results seem to be due to the bath oil formulation, i.e. vegetal polyunsaturated oil mixture with little liquid paraffin content. In conclusion, this formulation is very similar to normal epidermal lipids composition, and seems to represent a good compromise between the occlusive and integrative effects of topical emulsions.

Administration, Cutaneous↗
PubMed1989

The thickness, shape and arrangement of elastic fibres within the nuchal ligament from various animal species.

As shown by statistical evaluation carried out within various animal species (e.g. ruminants, equids, carnivores and proboscidates) the thickness of elastic fibres of the nuchal ligament is a specific character, i.e. unrelated to the somatic size of taxonomically different specimens. On the whole, ruminants are characterized by thicker elastic fibres than those from equids and carnivores. Moreover, within ruminants a correlation between the thickness of elastic fibres and body size has consistently been found. However, this condition occurs only when comparison between zoologically related species is drawn. During postnatal growth clearcut structural changes were brought to light, represented by the following phenomena simultaneously taking place: a) increase in thickness and lenght of preexisting elastic fibres; b) a progressive increase in the number of fibre splittings as well as of collaterals given off by individual fibres along their extension; c) neoformation of elastic fibres, and their addition to preexisting ones. In the bovines, already at six months of postnatal life, the elastic fibres of larger caliber have attained their full size.

Animals↗
PubMed1988

Improved metabolic properties of hexokinase-overloaded human erythrocytes.

Human erythrocytes were loaded with homogeneous hexokinase purified from human placenta (an enzyme species apparently identical to the erythrocyte enzyme), using a procedure of encapsulation based on hypotonic hemolysis, isotonic resealing and reannealing. The hexokinase-overloaded erythrocytes contained 4.77 +/- 0.75 IU of hexokinase activity per ml of packed erythrocytes, a value 15-times higher than that of corresponding unloaded or native red cells. The hexokinase-loaded erythrocytes were found to metabolize twice the amount of glucose consumed by the unloaded cells through a nearly doubled glycolytic activity, while the activity of the hexose monophosphate shunt pathway was unmodified. Estimates of glycolytic intermediates showed increased levels of most metabolites with respect to the unloaded erythrocytes, while the intracellular concentrations of adenine nucleotides and 2,3-bisphosphoglycerate were unaffected by entrapment of hexokinase. The new steady-state condition characterized by improved glycolytic function was demonstrated to be directly related to enhanced levels of hexokinase activity and not to the use of a rejuvenation solution during the procedure of entrapment. These results are consistent with suggestions by several investigators that glucose metabolism in human erythrocytes is regulated by hexokinase, and they open new perspectives for manipulating erythrocytes with the ultimate aim of improving their survival under different storage conditions.

Adenine Nucleotides↗
PubMed1988

Role of hexokinase in the regulation of erythrocyte hexose monophosphate pathway under oxidative stress.

Human erythrocytes overloaded with homogeneous human hexokinase (up to 15-times the activity of normal RBC) show almost unmodified rates of glucose metabolized in the HMP, however hexokinase-loaded RBC are able to metabolize 1.5 fold more glucose than controls through the HMP when an oxidizing agent like methylene blue (5 to 100 microM) is present. Similarly, RBC loaded with inactivating anti-hexokinase IgG (12 +/- 3% residual hexokinase activity) show HMP rates unchanged under resting conditions, but only 12% of the HMP rate found in normal controls under oxidative stress. These data provide clear evidence that the HMP rate under conditions of oxidative stress is controlled by hexokinase activity and suggest that RBC from patients with hexokinase deficiency are not able to increase the HMP rate under oxidative stress like erythrocytes from individuals with G6PD deficiency.

Erythrocytes↗
PubMed1988

Incidence and survival of brain tumors: a population-based study.

Since 1976 the Lombardy Cancer Registry (RTL) has recorded all malignant tumors and the benign tumors of the nervous system, bladder and liver occurring in the Varese province. The aims of this report are: to describe age-specific incidence rates of the different oncotypes of primary nervous system tumors (PNSTs) and to analyze the duration of survival of the patients according to the histotype of the neoplasm. From 1976 to 1981, the RTL recorded 498 PNST: 213 tumors of glial origin, 132 tumors of mesodermal tissues, 15 tumors of multipotential cell origin, 37 tumors of nerve roots, 8 of vascular origin, and 54 PNST in which the histotype was not specified. For tumors of glial origin, the 60-69 year age class showed the highest incidence rate: 16 per 100,000/year. The incidence rate of tumors of mesodermal tissues reached the maximum value of 7.9 per 100,000/year in the age group of 75 years and over. Tumors of multipotential cell origin had a maximum incidence of 2.2 in the 60-69 year age class. The probability of survival at 5 years after diagnosis was computed by the method of Kaplan and Meier, and the log rank procedure was used to test statistical differences among survivors. Tumors of glial origin, excluding ependymomas and papillomas of choroid plexus, had a 5-year survival probability of 14%. Age (categorized in less than or equal to 50 and greater than 50 years) and histologic grade (grades I + II and grades III + IV) were analyzed as prognostic factors for tumors of glial origin: a younger age was the most predictive prognostic factor in grade I + II tumors (probability of survival = 53% in the group less than or equal to 50 years vs 0 in the group greater than 50 years; p less than 0.005). In the less differentiated tumors there were no differences between the two age groups. Patients with tumors of mesodermal tissues had a 5-year probability of survival of 83%. Subjects younger than 50 years had a probability of survival of 95%, whereas older patients had a probability of 79%. For the other oncotypes, the 5-year survival probability was: 50% for tumors of multipotential cell origin, 63% for ependymomas and papillomas of the choroid plexus, 64% for tumors of vascular derivation, and 21% for PNST with not specified histotype.

Age Factors↗
PubMed1988

Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor.

To clarify the possible role of TNF and IL-1 in endotoxic shock, the lethality of rTNF (human and murine) and IL-1 in adrenalectomized mice was studied. Adrenalectomy, which has long been known to increase the susceptibility to endotoxin, rendered mice susceptible to TNF and IL-1 in terms of mortality. The lethality of endotoxin, TNF, or IL-1 was totally prevented by pretreatment with dexamethasone (minimal effective dose, 0.3 mg/Kg) but not by ibuprofen (10 mg/Kg).

Adrenal Cortex↗
PubMed1988

Induction of indoleamine dioxygenase by interferon in mice: a study with different recombinant interferons and various cytokines.

Since it is important the availability of a specific marker for interferon induction in vivo, we investigated the effect of different recombinant interferons and various cytokines on indoleamine 2,3-dioxygenase activity. Although with different magnitude, recombinant interferon-alpha A/D (Bgl II) hybrid, interferon-gamma and tumor necrosis factor, all increase the activity of this enzyme, whereas interleukin-1, recombinant interferon-alpha A and interferon-alpha D do not induce this activity in mice lung tissue. Dexamethasone is able to inhibit indoleamine 2,3-dioxygenase induction by lipopolysaccharide or by interferon-alpha A/D but it fails to prevent the induction by interferon-gamma.

Animals↗
PubMed1988

Chronic intrathecal cannulation affects hypothalamic beta-endorphin and met-enkephalin concentrations.

Beta-endorphin concentrations decrease and met-enkephalin concentrations increase in the hypothalamus of rats bearing a chronic intrathecal cannula. The modification of the concentrations of beta-endorphin is already present on day 1 after surgery, whereas met-enkephalin is affected starting on day 6, and both peptides are still modified on day 10. These results indicate that chronically cannulated rats are not to be considered normal animals.

Animals↗