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Biomedical subjects

G Carlin

Publications and source records attributed to G Carlin.

At least 19 recordsLinked to original sources
PubMed1992

Sulphasalazine inhibition of human granulocyte activation by inhibition of second messenger compounds.

The effects of sulphasalazine on the production of second messenger compounds in human granulocytes have been characterised by various stimuli. The increases in cytosolic calcium, inositol trisphosphate, diacylglycerol, and phosphatidic acid (all important mediators of intracellular signal transduction) triggered by stimulation were inhibited by sulphasalazine. The metabolites 5-amino-salicylic acid and sulphapyridine were less potent inhibitors than the mother compound. It is concluded that sulphasalazine inhibits the synthesis of phosphoinositide derived second messenger compounds at the level of phospholipase C or its regulatory guanosine 5'-triphosphate (GTP) binding protein. Inhibition of phosphatidic acid synthesis was either due to the same mechanism, or to interaction with a phospholipase D regulating GTP binding protein.

Aminosalicylic Acids↗
PubMed1991

Spermine: an anti-oxidant and anti-inflammatory agent.

This work demonstrates that spermine is a natural antioxidant and anti-inflammatory agent. It is found that: (1) Spermine inhibits the cytochrome C reduction initiated by FMLP- or PMA-stimulated human granulocytes. (2) Spermine inhibits the Fe(III)/xanthine oxidase stimulated lipid peroxidation of brain phospholipid liposomes. The antioxidative effect disappears at high Fe(III) concentrations. (3) Spermine forms a complex with Fe(II). (4) Spermine inhibits the Fe(II)-induced depolymerization of hyaluronic acid, and EDTA abolishes this effect. (5) Spermine or spermine-Fe(II) has no superoxide mimetic effect. These findings suggest that spermine has at least two antioxidative mechanisms of action: (I) Spermine inhibits the generation of the transport of superoxide radicals from stimulated granulocytes, and (II) Spermine inhibits the Haber-Weiss reaction by forming an unreactive chelate with Fe. Spermine thus prevents generation of destructive hydroxyl radicals.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

The hydroxylamine OXANOH and its reaction product, the nitroxide OXANO., act as complementary inhibitors of lipid peroxidation.

The effects of the nitroxide 2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl (OXANO.) and the corresponding hydroxylamine 2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine (OXANOH) on in vitro lipid peroxidation in rat liver microsomes and reconstituted lipid vesicles were investigated, and compared with those of some commonly used spin trapping agents. OXANO. and OXANOH (10-100 microM) inhibited iron-dependent lipid peroxidation, as did the spin trapping agents (10-100 mM). OXANO. mainly inhibited the rate of peroxidation, but caused only a small delay in the time of onset. OXANOH exerted its effect by delaying the onset of peroxidation in an antioxidant fashion, and also by inhibiting the rate. Higher concentrations of both substances were required to inhibit t-butylhydroperoxide-dependent lipid peroxidation. OXANO. was found to oxidize the ferrous-ADP complex required for initiation of peroxidation, and this is probably the basis of the inhibitory effect of this compound. Since the reaction of OXANO. tends to produce OXANOH and vice versa, either one could inhibit all reactions of lipid peroxidation.

Adenosine Diphosphate↗
PubMed1989

Inhibition of lipid peroxidation by spin labels. Relationships between structure and function.

Inhibition of lipid peroxidation by nitroxide radicals and their corresponding hydroxylamines was investigated. The nitroxides were either oxazolidines or piperidines, differing in substitution of the backbone of the molecule (a five or six-membered ring structure, respectively). Concentration requirements for 50% inhibition of microsomal lipid peroxidation varied from 340 to 6 microM for the nitroxides, and from 120 to 3 microM for the hydroxylamines, correlating with lipophilicity and chemical structure. Intramembrane concentrations required for 50% inhibition was independent of lipophilicity when peroxidation was initiated with ADP-Fe2+ but increased with lipophilicity when peroxidation was initiated with t-butylhydroperoxide. During studies of the kinetics of the inhibition, two modes were seen: a delay or a decreased rate of the process. The former mode was seen with the more lipophilic inhibitors. The mechanism of inhibition was similar for all nitroxides and consisted of the following three major components: blocking of primary initiation, prevention of secondary (peroxide-dependent) initiation, and scavenging of various lipoid radicals in the membrane, the major mode of action of the hydroxylamines. Inhibitory efficiency was interpreted in terms of steric hindrance, diffusibility, regeneration of inhibitor, and ability to interact with hydrophilic sites in a hydrophobic environment.

Adenosine Diphosphate↗
PubMed1989

Genetically engineered polymers of human CuZn superoxide dismutase. Biochemistry and serum half-lives.

CuZn superoxide dismutase is a highly stable dimer of identical subunits with a combined molecular mass of 32,000 daltons. Two human superoxide dismutase genes have been joined in the same translational reading frame, using spacers of different lengths, to encode single chain proteins consisting of two identical human superoxide dismutase subunits. The first construct encodes two directly linked subunits; the terminal glutamine codon of the first gene was changed to a methionine codon and followed immediately by the second gene. The second construct encodes two subunits linked by a 19-amino-acid human immunoglobulin IgA1 hinge sequence. Both constructs produce high levels of catalytically active superoxide dismutase when expressed in Escherichia coli. The protein containing the IgA1 hinge sequence forms polymers up to 750,000 in molecular weight, which are linked together noncovalently by the hydrophobic bonding of the dimer interface. The polymers are soluble, thermostable, and of near normal specific activity. Site-directed in vitro mutagenesis was used to inactivate one of the two human superoxide dismutase subunits. The resulting human superoxide dismutase polymers have approximately 50% activity, thus confirming that the products of both genes are catalytically active. Large amounts of individual polymeric forms have been purified from recombinant yeast and tested for serum stability in rats. The serum half-life is approximately 7 min for both the two-chain wild type human superoxide dismutase dimer (Mr 32,000) and the single chain molecule consisting of a human superoxide dismutase dimer covalently linked by the immunoglobulin hinge region (Mr 34,000), whereas the higher molecular weight polymers (Mr greater than or equal to 68,000) all have half-lives of approximately 145 min.

Amino Acid Sequence↗
PubMed1989

Inhibitory effects of sulfasalazine and related compounds on superoxide production by human polymorphonuclear leukocytes.

The inhibitory effects of sulfasalazine, some sulfasalazine-related compounds and indomethacin on superoxide production by human polymorphonuclear (PMN) leukocytes were studied. The inhibition of the chemotactic peptide (FMLP)-induced superoxide production, which is membrane receptor-mediated, was strongly dependent on the concentration both of the secretory stimulus and of the test compounds, indicating an interaction between the receptor and the test compound. Furthermore, a positive correlation was found between the lipophilicity of the compound and the degree of inhibition. However, when the receptor was by-passed by direct activation of the receptor-linked G protein by the use of fluoride ions as secretory stimuli, the test compounds still inhibited superoxide production. On the other hand, superoxide production by cells stimulated with phorbol ester was not inhibited by the test compounds. Furthermore, the production of phosphatidic acid was decreased in the presence of sulfasalazine, indicating impaired phosphoinositide metabolism. The inhibition of this metabolism was not due to increased intracellular concentrations of cyclic AMP, although sulfasalazine did inhibit cyclic nucleotide phosphodiesterase. We conclude that sulfasalazine attenuates superoxide production by PMN leukocytes at a post-receptor site of action at a step before the activation of protein kinase C, possibly by interfering with the phosphoinositide metabolism but independent of cyclic AMP.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1989

[Infections caused by central venous catheter used in surgery].

The central venous catheters, now usually adopted in surgical patients, present some potential septic risks, and the longer the catheter is in place, the more dangerous it is. The authors report their experience on 130 central venous catheters, out of which 96 were used for TPN administration and 34 for monitoring purposes. The catheters were introduced through subclavian, internal jugular or basilic veins, in accordance with a standardized technique. The observed infection percentage, caused by the catheters, was 7.7%; the infection was easily controlled by the catheter removal and a proper antibiotic therapy. The only death, surely due to sepsis, was caused by Candida fungus in an immunosuppressed female patient. Therefore the authors stress the importance to prevent septic complications in order to avoid fatal ones.

Bacterial Infections↗
PubMed1988

Studies on biosynthesis of alpha 2-antiplasmin in rat liver cells.

Biosynthesis, intracellular processing and secretion of alpha 2-antiplasmin (AP) were studied in primary cultures of rat hepatocytes by the pulse-chase technique. The experiments demonstrated that AP is present intracellularly as a 73 kD form and is secreted as a 79 kD form with affinity for human plasminogen kringles. Addition of human plasmin to the culture medium resulted in the formation of a 141 kD protein, probably a plasmin-AP complex, concomitantly with the disappearance of the 79 kD protein. The presence of tunicamycin, a blocker of N-linked glycosylation in the endoplasmic reticulum, during culture resulted in expression of a 63 kD form in medium and cell lysates. This latter form was unchanged after reduction and displayed affinity for human plasminogen kringles. The 79 kD form in the culture medium was resistant to treatment with endo-beta-N-acetylglucosaminidase-H while the intracellular 73 kD form was degraded to 63 kD, indicating glycosylation in the Golgi complex. It is concluded that rat AP is synthesized in a 63 kD form which is glycosylated in the endoplasmic reticulum to a 73 kD form; and that this in turn is trimmed and glycosylated further in the Golgi complex to the 79 kD form, which is secreted. The glycosylation is apparently not necessary for the secretion or for the affinity for human plasminogen kringles.

Absorption↗
PubMed1988

Increased production of malondialdehyde in patients with HIV infection.

The mean plasma content of malondialdehyde (MDA) in 30 patients in different stages of HIV infection was found to be about 30% higher than that in controls. The phenomenon was not correlated to the degree of immunodeficiency and was noted early in the course of the disease. This indicates a higher degree of basal lipid peroxidation, which might contribute to the tissue damage seen in these patients. A new reverse phase liquid chromatography method was used for quantitative measurements of MDA in plasma after reaction of this compound with thiobarbituric acid.

AIDS-Related Complex↗
PubMed1988

Inhibition of heme-promoted enzymatic lipid peroxidation by desferrioxamine and EDTA.

Oxyhemoglobin, methemoglobin and hematin were found to catalyze xanthine-oxidase-induced peroxidation of phospholipid liposomes, while oxy- and metmyoglobin were inactive in this respect. The peroxidation was inhibited by desferrioxamine and by EDTA. Peroxidation catalyzed by 0.4 microM oxyhemoglobin was decreased by 50% by approximately 2 microM desferrioxamine or 20 microM EDTA and completely inhibited by 10 microM desferrioxamine or 100 microM EDTA. Inhibition of hemoglobin-catalyzed peroxidation was not accompanied by any changes in the absorbance spectra of hemoglobin, indicating that the heme iron was not withdrawn by the inhibitor. Inhibition of hematin-catalyzed peroxidation by desferrioxamine may have been due to iron chelation and removal, as judged from changes in absorbance spectra. The peroxidation was apparently not dependent on hydrogen peroxide since catalase did not inhibit peroxidation but on the contrary promoted it in some cases.

Animals↗
PubMed1988

Peroxidation of phospholipids promoted by myeloperoxidase.

Myeloperoxidase was found to promote peroxidation of phospholipids under acidic conditions in the presence of hydrogen peroxide and iodide ions. The peroxidation was markedly enhanced by pyrophosphate-chelated ferric iron and was inhibited by desferrioxamine and superoxide dismutase. This observation adds lipid peroxidation to the oxidative damage caused by myeloperoxidase, which is a phagocytic cell enzyme involved in phagocyte-mediated cell destruction.

Humans↗
PubMed1987

Two forms of alpha 2-antiplasmin: post-traumatic changes in the rat.

The plasminogen-binding (PB-AP) and non-plasminogen-binding (NPB-AP) forms of alpha 2-antiplasmin (AP), were assayed in rat plasma by a modified rocket immunoelectrophoretic technique before and up to 48 h after turpentine-induced trauma, using an intermediary gel containing kringles 1-3 from plasminogen. The concentration of PB-AP was significantly elevated by 22% 24 h post-traumatically, while NPB-AP was decreased at that point in time, leaving the total AP level unchanged. Total AP increased by 57% during the period 24-48 h after trauma, mainly on account of increases in the NPB-AP form. It is concluded that the plasma level of AP can remain unchanged in spite of increased fibrinolysis inhibition, owing to a relative increase in the functionally more active PB-AP.

Animals↗
PubMed1985

Effect of anti-inflammatory drugs on xanthine oxidase and xanthine oxidase induced depolymerization of hyaluronic acid.

The inhibitory effect of various anti-inflammatory drugs on the xanthine oxidase derived depolymerization of hyaluronic acid was studied. The depolymerization was assayed by repeated viscosity measurements. By using a low xanthine oxidase activity, the decrease in viscosity with time followed first order reaction kinetics and was therefore suitable for kinetic analysis. The xanthine oxidase activity was monitored by assay of O2-consumption with a Clark-electrode and by assay of urate production. We present evidence that salicylic, acetylsalicylic, gentisic and azodisalicylic acid and sulfasalazine inhibit the production of oxygen-derived free radicals by xanthine oxidase. We found that sulfapyridine, 5-aminosalicylic acid, allopurinol, mannitol, glucuronic acid and N-acetylglucosamine in addition to the earlier studied drugs, paracetamol, ibuprofen, benoxaprofen and gentisic acid exert their effect via scavenging of free radicals. These drugs had very little effect on the enzyme activity.

Anti-Inflammatory Agents↗
PubMed1985

Peroxidation of linolenic acid promoted by human polymorphonuclear leucocytes.

Human polymorphonuclear leucocytes were found to promote peroxidation linolenic acid micelles. The peroxidation was markedly enhanced by addition of ferric iron, either in the form of chloride, ADP-complex or EDTA to the phosphate-buffered reaction mixture. The leucocyte oxygen burst was induced by the addition of the lipid micelles, and no other stimulatory agent was therefore required. Pretreatment of the leucocytes with cytochalasin B did not inhibit t.e lipid peroxidation which indicates that phagocytosis was not part of the peroxidative mechanism. Lipid peroxidation was inhibited by alpha-tocopherol acetate, butylated hydroxytoluene, manganese ions and desferrioxamine but not by superoxide dismutase, catalase or the hydroxyl radical scavenger dimethylsulfoxide. Lipid peroxidation promoted by xanthine oxidase, was studied for comparison. This was inhibited by superoxide dismutase, indicating that xanthine oxidase, in contrast to leucocytes, promotes lipid peroxidation via a superoxide-dependent mechanism. Manganese ions and butylated hydroxytoluene, and to a lesser extent alpha-tocopherol, were also inhibitors. The leucocyte promoted lipid peroxidation is similar to the well-known peroxidation promoted by microsomal NADPH-cytochrome P450 reductase, which also is not induced by superoxide radicals. Peroxidation of lipids may be a mechanism whereby granulocytes express tissue damage in for example inflammation and ischaemia.

Catalase↗
PubMed1985

Peroxidation of liposomes promoted by human polymorphonuclear leucocytes.

Human polymorphonuclear leucocytes were found to promote peroxidation of phospholipid liposomes upon stimulation by phorbol myristate acetate. Peroxidation required the presence of either pyrophosphate-chelated or ADP-chelated iron, whereas iron chelated to EDTA or ATP had no effect. Peroxidation was also catalyzed by ferritin, but not by transferrin. Superoxide dismutase abolished the peroxidation, whereas catalase and apparently also the hydroxyl radical scavenger dimethyl sulphoxide were inactive, indicating that the peroxidation was mediated by superoxide radicals but not by hydrogen peroxide or hydroxyl radicals. Xanthine oxidase-promoted peroxidation was studied for comparison and showed similar characteristics except that transferrin catalyzed the peroxidation. Peroxidation of membrane lipids may be a mechanism whereby granulocytes cause tissue damage in inflammation. The drugs paracetamol, gentisic acid and 5-aminosalicylic acid inhibited lipid peroxidation, probably through their ability to react with the superoxide anion.

Cytochrome c Group↗
PubMed1979

Severity and prognosis after early excisions from one to twenty percent of the body surface area.

The authors review 101 small and medium early excisions with immediate grafting. They study several parameters concerning the severity of the burn, the time and the duration of the surgical procedure, the blood losses, the effect on the protidemia during the shock period, the duration of the hospital care, the septicemic risk, the mortality, and the functional and cosmetic results. They come to the conclusion that, under 15% of the body surface area, early excision can be done at one single operation with hardly any risk, and that it is better to perform it as soon as possible (before 12 hours if possible). With a good splinting and a daily rehabilitation, the cosmetic and functional results are very satisfactory.

Blood Volume↗
PubMed1979

Effect of infusion of dextran 70 on fibrinolysis inhibition activity in human serum.

The effect of dextran on fibrinolysis inhibition activity was studied in the serum of normal (uninjured) persons and of post-traumatic patients. An intravenous infusion of 500 ml dextran 70 significantly decreased the fibrinolysis inhibition activity in the serum in both groups. The decrease was greater in the trauma group. Treatment with dextran in the post-traumatic phase may therefore diminish the risk of development of complication due to thromboembolism.

Adolescent↗