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Biomedical subjects

M Costanzo

Publications and source records attributed to M Costanzo.

At least 37 records · Page 2Linked to original sources
PubMed1994

Interactions of monoamine oxidase inhibitors, N-acetylenic analogues of tryptamine, with rat liver microsomal cytochrome P450.

Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time-dependent manner. Only tertiary aliphatic amines constituted the substrate for P450-dependent N-demethylase activity, with comparable kinetic parameters. The N-demethylated metabolites were identified by thin-layer chromatography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.

Acetylene↗
PubMed1993

Tumor necrosis factor activation of the sphingomyelin pathway signals nuclear factor kappa B translocation in intact HL-60 cells.

Recent investigations suggest that tumor necrosis factor (TNF)-alpha may utilize the sphingomyelin pathway for signal transduction. Signaling in this system involves hydrolysis of sphingomyelin to ceramide by action of a neutral sphingomyelinase and stimulation of a ceramide-activated protein kinase (Dressler, K. A., Mathias, S., and Kolesnick, R. N. (1992) Science 255, 1715-1718). To clarify the role of this pathway in TNF action, the present studies assessed the effect of the sphingomyelin pathway on activation of nuclear factor kappa B (NF-kappa B), an event considered integral to the transfer of the TNF message to the cell nucleus. As shown previously, TNF (1 nM) induced a marked increase in nuclear NF-kappa B binding in human leukemia (HL-60) cells within 5 min, and elevated binding was detected for as long as 1 h. Addition of a maximally effective concentration of sphingomyelinase, 0.1 units.ml-1, induced a 50% reduction in sphingomyelin content by 5 min from a basal level of 560 pmol.10(6) cells-1 and a quantitative increase in ceramide levels from 89 pmol.10(6) cells-1. Sphingomyelinase 0.1 units.ml-1 also induced an increase in nuclear NF-kappa B binding within 5 min, an effect measurable for as long as 1 h. As little as 1 x 10(-5) units.ml-1 sphingomyelinase was effective and a maximal effect occurred with 1 x 10(-3) units.ml-1. A cell-permeable ceramide analog, C8-ceramide, which mimics biologic effects of TNF-alpha, also enhanced nuclear NF-kappa B activation within minutes. In contrast, addition of a phospholipase C or a synthetic diacylglycerol (DG) analog, 1,2-dioctanoylglycerol, failed to enhance nuclear NF-kappa B binding despite large increases in cellular DG content. Further, TNF-alpha induced elevation in ceramide content by 2 min to 185% of control but did not affect DG levels. These studies provide evidence that stimulation of the sphingomyelin pathway leads to NF-kappa B activation in HL-60 cells.

Arachidonic Acid↗
PubMed1986

Platelet and coagulation functions during triphasic oestrogen-progestogen treatment.

The purpose of this investigation was the longitudinal evaluation of the hemostatic system before and after 1, 3, and 6 months of treatment with a triphasic oestrogen-progestogen combination. No changes of circulating platelet aggregates, as an index of in vivo platelet aggregability, and of megathrombocytes, an indirect evaluation of accelerated thrombocytopoiesis, were observed. A very slight, but significant, increase of Fibrinopeptide A (FPA), a reliable index of thrombin formation, was found only after 1 month of treatment; after 3 and 6 months, the increase of FPA was not homogeneous and not significant. Antithrombin III activity (AT III) showed no modifications after the first month; after 3 months AT III increased to a small extent, and after 6 months it was similar to basal values. Our findings indicate that the triphasic combination does not modify platelet functions and induces a low-degree activation of coagulation counteracted by an increased activity of the physiological inhibitors of blood clotting.

Adolescent↗
PubMed1985

The biochemical and behavioral effects of phospholipase A2 and morphine microinjections in the periaqueductal gray of the rat.

In order to characterize the in vivo action of phospholipase A2 (PLA2) on opiate receptors and opiate-induced behaviors, the effects of injections of PLA2 into the periaqueductal gray region (PAG) of the rat were assessed on free fatty acid (FFA) release, opiate-binding levels, and morphine-induced behaviors. Rats received bilateral PAG injections of 2 micrograms of PLA2 while anesthetized. One hour later, regions around the cannulae tracts in PLA2-treated rats contained over 2.5 times more FFA than saline-injected controls, and 3H-dihydromorphine binding was reduced on average more than 70%. In another series of experiments, conscious rats were given 2 micrograms of PLA2 prior to 10 micrograms of morphine through cannulae chronically implanted into the PAG. PLA2 did not significantly attenuate morphine-induced analgesia as measured by the tail-flick test to radiant heat, but did prevent the explosive motor behavior observed following morphine injections alone. PLA2 by itself did not induce analgesia, but did cause explosive motor behavior 2 hr after the injections. Neither lysophosphatidylcholine nor trypsin resulted in motor seizures following PAG injections. It was concluded that the behavioral effects of PLA2 result from the unique properties of the enzyme, rather than generalized membrane damage, and that the opioid sites and mechanisms that mediate analgesia are different from those associated with explosive motor behavior.

Analgesia↗
PubMed1985

Specific binding and metabolism of (-)- and (+)-[3H]-nicotine in isolated rat hepatocytes and hepatocyte membranes.

The specific binding of (-)- and (+)-[3H]-nicotine, as well as their relative rates of metabolism, were investigated in isolated rat hepatocytes and hepatocyte membranes. A Scatchard plot of both [3H]-enantiomers revealed two components, with the higher affinity site having Kd values of 2 X 10(-10) and 3 X 10(-9) M and Bmax values of 5 X 10(-15) and 4 X 10(-15) moles/mg protein for the (-)- and (+)-enantiomers, respectively. The lower affinity site for both enantiomers had a Kd of 4 X 10(-9) M and Bmax of 5 X 10(-14) moles/mg protein. The pH optimum of binding was in the higher pH range, in contrast to brain membranes where the optimum was 6.5 involving the protonated form of nicotine. A good correlation was observed between the pharmacologic potency of a group of nicotine analogues and their ability to bind to intact and hepatocyte membranes. The rate of conversion of nicotine to cotinine in hepatocytes membranes. The rate of conversion of nicotine to cotinine in hepatocytes is related to the degree of binding and accumulation. The results are discussed in terms of the possible relationship of the nicotine binding and translocation to its metabolism.

Animals↗
PubMed1984

Bacteriophage SPO1 genes 33 and 34. Location and primary structure of genes encoding regulatory subunits of Bacillus subtilis RNA polymerase.

Bacteriophage SPO1 gene 33 and 34 products are required for SPO1 late gene transcription. Both proteins bind to the core RNA polymerase of the Bacillus subtilis host to direct the recognition of SPO1 late gene promoters, whose sequences differ from those of SPO1 early and middle gene promoters. We have located and cloned the genes for these two regulatory proteins, and have engineered their expression in Escherichia coli by placing them under the control of the bacteriophage lambda PL promoter. Nucleotide sequence analysis indicated that genes 33 and 34 overlap by 4 base-pairs and encode highly charged, slightly basic proteins of molecular weight 11,902 and 23,677, respectively.

Amino Acid Sequence↗
PubMed1984

Overproduction and purification of a bacteriophage SPO1-encoded RNA polymerase sigma factor.

Gene 28 of bacteriophage SPO1 encodes an RNA polymerase sigma factor sigma gp28, which replaces the host Bacillus subtilis sigma subunit sigma 55, to alter the promoter recognition specificity of RNA polymerase. A fragment of SPO1 DNA containing gene 28 was placed under the control of the PL promoter of bacteriophage lambda in an Escherichia coli expression vector. When transcription of gene 28 was induced by derepression of PL, the sigma gp28 synthesized constituted several per cent of total cellular protein. Sigma gp28 purified from these cells was able to confer specificity for SPO1 middle gene promoters upon B. subtilis core RNA polymerase, and also enabled E. coli core RNA polymerase to recognize and initiate transcription from an SPO1 middle gene promoter.

Bacillus subtilis↗
PubMed1983

Structure of a Bacillus subtilis bacteriophage SPO1 gene encoding RNA polymerase sigma factor.

Gene 28 of Bacillus subtilis bacteriophage SPO1 codes for a regulatory protein, a sigma factor known as sigma gp28, that binds to the bacterial core RNA polymerase to direct the recognition of phage middle gene promoters. middle promoters exhibit distinctive and conserved nucleotide sequences in two regions centered about 10 and 35 base pairs upstream from the start point of mRNA synthesis. Here we report the cloning of gene 28 and its complete nucleotide sequence. We infer that sigma gp28 is a 25,707-dalton protein of 220 amino acids. Neither the nucleotide sequence of gene 28 nor the inferred amino acid sequence of sigma gp28 exhibits extensive homology to the gene or protein sequence of Escherichia coli sigma factor.

Amino Acid Sequence↗
PubMed1983

Bacteriophage SPO1 gene 27: location and nucleotide sequence.

Bacteriophage SPO1 gene 27, whose product is required for late gene transcription and DNA replication, has been cloned in Escherichia coli, and its complete nucleotide sequence has been determined. We infer that the product of gene 27 is a highly basic 17,518-dalton protein of 155 amino acids. The gene for this regulatory protein is transcribed from two promoters: an early promoter situated before the adjacent upstream gene 28 and a middle promoter located between genes 28 and 27.

Bacillus subtilis↗
PubMedDate not supplied

Deep vein thrombosis of the legs: new therapy by means of low molecular weight heparins.

This open controlled study compared the effects of subcutaneous administration of two types of heparin in two groups of 40 patients each with deep vein thrombosis. One group received calcium heparin and the other received low molecular weight heparin for 40 days in each case. Patients receiving low molecular weight heparin showed a greater increase in inhibition of activated factor X than those receiving calcium heparin. Both drugs slightly reduced activated partial thromboplastin time. No patient experienced pulmonary embolism during the study. At the end of the study, maximum venous outflow was significantly higher in patients given low molecular weight heparin than in those given calcium heparin. No major side-effects were observed. This study showed that: (a) the anti-thrombotic effect of low molecular weight heparin was greater than for calcium heparin; and (b) low molecular weight heparin improved maximum venous outflow in approximately half of the patients, possibly by promoting or accelerating recanalization of the vessel.

Clinical Trials as Topic↗
PubMedDate not supplied

Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo.

The efficacy and tolerability of Serratia peptidase were evaluated in a multicentre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7-8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7-8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflammatory, anti-oedemic and fibrinolytic activity and acts rapidly on localized inflammation.

Acute Disease↗