Search PubMed⌕ Search

Biomedical subjects

A Pinson

Publications and source records attributed to A Pinson.

At least 19 recordsLinked to original sources
PubMed2000

Protection of thrombin receptor expression under hypoxia.

Thrombin receptor (ThR) plays a significant role in myocyte contractility and hypertrophy. Heart myocyte ischemic damage, caused by insufficient blood supply, is the leading cause of heart infarction. Here we demonstrate that when primary myocyte cultures are subjected to hypoxic stress, ThR mRNA levels are reduced markedly. This takes place also in vivo in a model of ischemic pig heart, exhibiting reduced levels of ThR compared with normal heart sections. Prior activation of ThR however, by either thrombin receptor-activating peptide (TRAP) or by alpha-thrombin resulted in full protection of ThR mRNA levels under hypoxia. The effect appeared specific to ThR because the addition of TRAP did not affect the hypoxic damage as shown by the levels of lactic dehydrogenase release and up-regulated GLUT-1, a glucose transporter gene. This protection effect took place not only in primary myocytes but also in NIH3T3 fibroblasts. ThR protection occurs via specific cell signaling events because activation of the receptor by TRAP, following interruption of the signaling cascade by calphostin C, a protein kinase C inhibitor, resulted in loss of ThR mRNA protection. Because Ras and Src are part of the ThR signaling cascade, the introduction of either dominant ras or src oncogenes to NIH3T3 murine fibroblasts gave rise to similar protection of ThR mRNA levels under hypoxic conditions without the exogenous addition of TRAP. Likewise, ThR mRNA protection was obtained after transfection with proto-oncogene vav. The 95-kDa protein Vav undergoes tyrosine phosphorylation after ThR activation, serving thus as part of the receptor machinery cascade. We therefore conclude that the initiation of the signaling cascades either exogenously by TRAP or within the cell via src or ras, as well as via vav oncogene interconnecting G-binding protein to the tyrosine kinase pathway, ultimately results in ThR protection under hypoxia. We present hereby, a novel concept of activated receptors, which under minimal oxygen tension protect their otherwise decaying mRNA. Maintaining the level of ThR that plays an active role in normal myocyte function may provide a significant repair mechanism in ischemic tissue, assisting in the regaining of normal myocyte functions.

3T3 Cells↗
PubMed1998

Both hydroxylamine and nitroxide protect cardiomyocytes from oxidative stress.

The unique anti-oxidative activity of nitroxide radicals protecting against reactive oxygen-derived species (ROS) has been recently demonstrated in several model systems. The present study focuses on the activity of nitroxide and of its reduced form in cultured rat ventricular cardiomyocytes exposed to O2.- and H2O2 generated by hypoxanthine (HX) and xanthine oxidase (XO). To evaluate cell injury, spontaneous beating, leakage of lactate dehydrogenase (LDH), and depletion of cellular ATP were determined. The protective effect of 4-OH-2,2,6,6-tetramethyl-piperidine-N-oxyl (TPL) was compared with that of 4-OH-2,2,6,6-tetramethyl-1-hydroxypiperidine (TPL-H) and of several common anti-oxidants. A rapid exchange between TPL and TPL-H, is mediated by cellular metabolism and through reactions with ROS. In particular, TPL under O2.- flux is oxidized to oxo-ammonium cation (TPL+) which comproportionates with TPL-H yielding two nitroxide radicals. Because this exchange limits the distinction between the biological activities of TPL and TPL-H, NADH which can reduce TPL+ was included in order to maintain the nitroxide in its reduced form. The results demonstrate that both TPL and TPL-H protect cardiomyocytes against beating loss and LDH leakage. Conversely, cellular ATP depletion induced by HX/XO is inhibited by TPL-H, though not by TPL, suggesting that different mechanisms underlie their protective activities. Through a flip-flop between the two forms, which coexist in the system, the levels of TPL-H and TPL are continuously replenished. The conversion, upon reaction, of each antioxidant into the other one enables them, contrary to common antioxidants which operate in a stoichiometric mode, to act catalytically.

Animals↗
PubMed1998

Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells.

Our previous studies in iron-loaded rat heart cells showed that in vitro iron loading results in peroxidative injury, manifested in a marked decrease in rate and amplitude of heart cell contractility and rhythmicity, which is correctable by treatment with deferoxamine (DF). In the present studies we explored the role of mitochondrial damage in myocardial iron toxicity. Iron loading by 24-hour incubation with 0.36 mmol/L ferric ammonium citrate resulted in a decrease in the activity of nicotinamide adenine dinucleotide (NADH)-cytochrome c oxidoreductase (complex I+III) to 35.3%+/-11.2% of the value in untreated controls; of succinate-cytochrome c oxidoreductase (complex II+III) to 57.4%+/-3.1%; and of succinate dehydrogenase to 63.5%+/-12.6% (p < 0.001 in all cases). The decrease in activity of other mitochondrial enzymes, including NADH-ferricyanide reductase, succinate ubiquinone oxidoreductase (complex II), cytochrome c oxidase (complex IV), and ubiquinol cytochrome c oxidoreductase (complex III), was less impressive and ranged from 71.5%+/-15.8% to 91.5%+/-14.6% of controls. That the observed loss of respiratory enzyme activity was a specific effect of iron toxicity was clearly demonstrated by the complete restoration of enzyme activities by in vitro iron chelation therapy. Sequential treatment with iron and doxorubicin caused a loss of complex I+III and complex II+III activity that was greater than that seen with either agent alone but was only partially correctable by DF treatment. Alterations in cellular adenosine triphosphate measurements paralleled very closely the changes observed in respiratory complex activity. These findings demonstrate for the first time the impairment of cardiac mitochondrial respiratory enzyme activity caused by iron loading at conditions formerly shown to produce severe abnormalities in contractility and rhythmicity.

Adenosine Triphosphate↗
PubMed1996

Glucose is essential for the initiation of fatty acid oxidation in ATP-depleted cultured ventricular myocytes.

Cultured cardiac myocytes were depleted of ATP by incubation with oligomycin (1 mg/ml). Then the ability of the cells to oxidize various substrates and to restore ATP levels was studied. Following ATP depletion, the cells were found to be able to oxidize glucose given alone, but not palmitate. However, with both substrates, palmitate was oxidized in the presence of glucose and ATP recovery was enhanced. Pyruvate had a minor effect on palmitate oxidation, while acetate given alone was oxidized, but did not enhance cellular ATP content. These results show that glucose is essential for restoration of mitochondrial function and the coupling between oxidation and ATP synthesis.

Adenosine Triphosphate↗
PubMed1996

Role of iron in the potentiation of anthracycline cardiotoxicity: identification of heart cell mitochondria as a major site of iron-anthracycline interaction.

The role of iron in anthracycline toxicity was studied in rats in vivo in intact animals and in vitro in heart cell cultures. In animals treated with 8 mg/kg doxorubicin, iron loading resulted in severe weight loss and a twofold increase in rate of mortality. Studies in cultured heart cells aimed at defining the subcellular target of interaction between iron and anthracycline toxicity showed no evidence of anthracycline-induced damage to sarcolemmal thiolic enzymes represented by 5'-nucleotidase and only a limited increase in lysosomal fragility as monitored by an increase in beta-hexosaminidase activity in cell homogenates and its release into the culture medium. By contrast, doxorubicin treatment resulted in a marked inhibition of mitochondrial function as monitored by a decrease in carbon 14-labeled palmitate utilization, to 33% +/- 4% of controls, and prior iron loading resulted in a further decrease in palmitate utilization, to 18% +/- 3% of controls. Conversely, iron-chelation treatment by either deferoxamine or deferiprone (L1) eliminated the harmful effects of iron loading and resulted in a partial inhibition of doxorubicin toxicity in both normal and iron-loaded cells. Our studies represent the first demonstration in intact animals of the potentiation of anthracycline toxicity by iron overload. They also indicate that mitochondria represent an important target of combined iron-anthracycline toxicity. These observations provide new insights into the mechanism of anthracycline cardiotoxicity and may be useful in developing better strategies for tumor therapy.

Animals↗
PubMed1996

Oxygen deprivation and reoxygenation augment prostacyclin synthesis in cultured ventricular myocytes.

Prostacyclin production in cultured cardiomyocytes is not induced by cellular ATP depletion per se, suggesting that the mechanism of ischemic injury is more complex. In the present study we subjected cultured ventricular myocytes to 'simulated ischemia' followed by reoxygenation. A slight increase in 6-keto-PGF(1 alpha) (the stable metabolite of PGI(2)) was found during 'ischemia', which continued to increase markedly during reoxygenation. PGE(2) levels were pronouncedly enhanced during ischemia but decreased during reoxygenation, and TXB(2) levels remained undetectable throughout. These findings reflect a cardiomyocyte response to anoxic injury, suggesting that they act to protect against cardiac injury by producing the potent vasodilators PGI(2) and PGE(2) during ischemia and reoxygenation.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Prevention of anthracycline cardiotoxicity by iron chelation.

The use of anthracycline antineoplastic drugs is limited by a cumulative, dose-dependent toxicity to the heart. Of the cellular organelles proposed as possible primary sites of anthracycline toxicity, the mitochondrial membrane appears to be most likely target. Cardiolipin, a major phospholipid component of the inner mitochondrial membrane is rich in polyunsaturated fatty acids and is particularly susceptible to peroxidative injury by harmful radicals produced by redox cycling of anthracyclines. This, in turn, leads to the inactivation of key enzymes in the mitochondrial respiratory chain. Since the formation of free radicals is catalyzed by iron through the Haber-Weiss reaction, it was hypothesized that iron depletion by deferoxamine (DFO) may limit anthracycline cardiotoxicity. Recent studies indicate that iron-loading aggravates doxorubicin cardiotoxicity by enhancing mitochondrial damage, and this can be prevented by prior DFO treatment. Although these observations are intriguing, further studies are required to show that the cardioprotective effects of DFO do not interfere with the therapeutic, antitumoral action of anthracyclines.

Antibiotics, Antineoplastic↗
PubMed1995

Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide?

The aim of the research was to study the role played by extracellular O2-radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when > 80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H2O2 is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Ability of the orally effective iron chelators dimethyl- and diethyl-hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells.

In view of the profound functional and structural abnormalities shown in our previous studies in cultured, iron-loaded rat heart cells, we have examined the ability of the orally effective iron chelators dimethyl-3-hydroxypyrid-4-one (DMHP or L1) and diethyl-3-hydroxy-pyrid-4-one (DEHP or CP94) and of deferoxamine (DF) to reverse the damage caused by iron loading to heart cell organelles. At a concentration of 1.0 mmol/L, all three iron chelators were equally efficient in removing iron and restoring the activity of the thiolic sarcolemmal enzymes 5'-nucleotidase and Na,K,ATPase. However, at 0.1 mmol/L DMHP and DEHP were less effective than DF both in their iron-mobilizing effect and in promoting thiolic enzyme recovery. The superior efficiency of DF at low concentrations illustrates the advantage of the hexadentate chelating action of DF as compared with bidentate chelators such as DMHP and DEHP requiring a 3 to 1 molar ratio to iron for optimal effect. In contrast to its beneficial effect on sarcolemmal enzyme activity, iron chelation was unable to reverse the increase in beta-hexosaminidase activity caused by abnormal lysosomal fragility. Our study demonstrates for the first time that iron-induced peroxidative damage to the myocardial cell is associated with a marked loss of Na,K,ATPase activity, an enzyme with a major role in the maintenance of cellular resting potential. The timing of this damage and the restoration of Na,K,ATPase function by iron-chelating treatment suggest a cause-and-effect relationship between the observed injury to the sarcolemmal enzyme and the reversible electrophysiologic abnormalities observed in the same heart culture system in our previous studies.

5'-Nucleotidase↗
PubMed1994

High oligomycin concentrations augment 6-keto-PGF1 alpha production in ventricular cardiomyocytes.

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 micrograms/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF1 alpha production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF1 alpha was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP2-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis.

OBJECTIVE: The process of coronary collateral development is poorly understood. It is assumed that particular angiogenic factors are upregulated during episodes of myocardial ischaemia and act as a trigger for neovascularisation. However, the identity of these factors is unknown. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be hypoxia inducible, so this factor may mediate ischaemia induced angiogenesis in the heart. The aim of this study was to examine hypoxia inducibility of VEGF in cultured myocardial cells as well as in normally perfused and ischaemic porcine myocardium. METHODS: (1) In vitro experiment: cultured rat myocardial cells were subjected to hypoxia, and steady state levels of VEGF mRNA were measured after 2 and 4 h of hypoxia. (2) In vivo experiment: myocardial ischaemia in pigs hearts was induced by repeated 2-10 min left anterior descending coronary artery occlusions, separated by 20 min of reperfusion. Hearts were retrieved after 6 h of intermittent ischaemia. Total RNA was extracted from normal and ischaemic zones of the heart and processed for RNA blot hybridisation analysis. RESULTS: In vitro experiment: as soon as 2-4 h after exposure of cultures to hypoxia, VEGF mRNA levels were significantly raised (6-10-fold). In vivo experiment: VEGF expression was significantly augmented in the ischaemic territory of the myocardium (three- to fivefold induction). Furthermore, polymerase chain reaction amplification of the reverse transcribed mRNA showed increased production of multiple forms of differentially spliced VEGF mRNA in the ischaemic myocardium. CONCLUSIONS: VEGF production in the myocardium is significantly upregulated by hypoxia in vitro and by ischaemia in vivo. These results suggest that VEGF is a likely mediator in the natural process of ischaemia induced myocardial neovascularisation.

Animals↗
PubMed1993

Alpha- and beta-adrenergic stimulation of protein synthesis in cultured adult ventricular cardiomyocytes.

The effect of the alpha 1-adrenoceptor agonist phenylephrine (PE, 1-10 microM) and the beta-adrenoceptor agonist isoprenaline (ISO, 1-10 microM) on protein synthesis and ultrastructure of ventricular cardiomyocytes from adult rat in culture (6 days in medium 199 plus 20% fetal calf serum) was studied. In these cultures cardiomyocytes were spread, but not spontaneously contractile. ISO and PE significantly increased total cell protein and incorporation of (14C)-phenylalanine within 24 h of exposure. These effects were inhibited by the antagonists propranolol and prazosin, respectively. The incorporation of (14C)-uridine was stimulated only by PE but not ISO. Induction of fetal BB-isoform of cytosolic creatine kinase was also caused only by PE but not ISO. The ultrastructure of PE-treated cardiomyocytes was altered as compared to controls, by a greater number of Golgi complexes, denser myofibrillar structures and the appearance of paracrystalline bands in mitochondrial matrices. In conclusion, in this culture model the protein synthesis of cardiomyocytes can be stimulated, independently of the contractility, by either alpha 1- or beta-adrenoceptor agonists. Catecholamines differ, however, in their effects on specific cellular proteins and structures. Only alpha 1-adrenergic stimulation leads to a "fetal shift" in the expression of CK-isoforms.

Animals↗
PubMed1993

The role of iron and iron chelators in anthracycline cardiotoxicity.

The redox cycling of anthracyclines promotes the formation of free radicals which are believed to play a central role in their cardiotoxicity. A number of observations indicate that the mechanism of the antineoplastic effect of anthracyclines is independent of their cardiotoxic effect and that it may be possible to prevent toxicity without interfering with therapeutic effect. Iron plays an important role in anthracycline toxicity by promoting the conversion of superoxide into highly toxic hydroxyl radicals through the Haber-Weiss reaction. Conversely, iron deprivation by its high-affinity binding to iron chelating compounds may inhibit anthracycline toxicity by interfering with free radical formation. ICRF-187, a bispiperazonedione which is hydrolyzed intracellularly into a bidentate chelator resembling EDTA, is able to decrease adriamycin-induced free hydroxyl radical formation and to prevent the development of clinical cardiac toxicity in patients receiving long-term anthracycline therapy. Our studies in rat heart cell cultures have shown that iron overload aggravates anthracycline toxicity and that this interaction can be prevented by prior iron chelating treatment. Since iron overload caused by multiple blood transfusions and bone marrow failure is a common condition in patients requiring anthracycline therapy, these observations may have significant clinical implications to the prevention of anthracycline cardiotoxicity.

Animals↗
PubMed1993

Anthracycline toxicity is potentiated by iron and inhibited by deferoxamine: studies in rat heart cells in culture.

The interrelation between iron, iron chelation, and anthracycline toxicity was investigated in a heart cell culture system. Two indicators of cellular damage have been used, lactate dehydrogenase (LDH) release and cell contractility. Both of these indicators have shown a marked increase in doxorubicin toxicity by prior iron loading. This was not a simple additive effect, because at the concentrations used, iron had only a minimal effect on LDH release and no effect at all on contractility, whereas doxorubicin had only a minor effect on contractility. Deferoxamine (DF) treatment of iron-loaded heart cells resulted in a marked decrease in anthracycline toxicity as judged both by LDH leakage and cell contractility. However, DF treatment of normal heart cells had no measurable protective effect against doxorubicin toxicity, whether DF was administered before or simultaneously with doxorubicin. Doxorubicin treatment did not alter cellular malondialdehyde (MDA) concentrations in either normal or iron-loaded cells. Conversely, the protective effect of DF in iron-loaded cells and its failure to prevent anthracycline toxicity in normal cells were both associated with a significant decrease in MDA measurements. Our data indicate that iron overload aggravates anthracycline toxicity and that this interaction may be prevented by effective iron chelating therapy. Because patients requiring anthracycline therapy often have increased tissue iron stores caused by multiple blood transfusions and bone marrow suppression, our observations may have important implications for the prevention of anthracycline toxicity.

Animals↗
PubMed1993

Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility.

The mechanism of damage to myocardial subcellular organelles was studied in iron-loaded rat myocardial cells in culture in an attempt to identify the primary target of iron's toxic effects. Lysosomes and sarcolemmal membranes were purified by fractionation of the postnuclear supernatant on a 6.7% colloidal polyvinylpyrrolidone-coated silica gradient. After 24-hour incubation with ferric ammonium citrate at a concentration of 20 micrograms/ml (0.36 mmol/L) iron, a selective depletion of polyunsaturated fatty acids was found in whole-cell homogenates, as well as in the postnuclear supernatant and sediment. Iron loading resulted in a sharp increase in the total activity of the lysosomal enzyme beta-hexosaminidase in unfractionated whole-cell homogenates, increased free enzyme activity, and loss of latent activity indicating increased lysosomal fragility. Conversely, iron loading resulted in a marked decrease in the activity of the sarcolemmal enzyme 5'-nucleotidase and a significant loss of total protein sulfhydryl group content. These studies in cultured heart cells are in agreement with previous observations indicating increased lysosomal fragility in iron-loaded hepatic and splenic tissues, attributed to increased membrane lipid peroxidation. In addition, the marked decrease in sarcolemmal 5'-nucleotidase activity and in total protein sulfhydryl group content imply that iron-induced peroxidative damage to membrane proteins may be a more important mechanism in the pathogenesis of altered myocardial function in the iron-loaded heart than formerly was recognized.

5'-Nucleotidase↗
PubMed1992

Anoxic injury accelerates phosphatidylcholine degradation in cultured cardiac myocytes by phospholipase C.

In neonatal cultured cardiac myocytes under normoxic conditions, 32Pi incorporation pattern into various phospholipids, and double-labeling experiments with 32Pi and [3H]methyl choline, suggest that phosphatidylcholine and phosphatidylinositol are turned over rapidly, whereas the turnover of phosphatidylethanolamine is probably much slower. While increased levels of the corresponding lysophospholipids were not found under anoxia, release of diacylglycerol and phosphorylcholine was observed. These data strongly suggest that phospholipase C, and not phospholipase A2, is involved in phospholipid degradation in cultured cardiomyocytes under anoxic conditions.

Animals↗
PubMed1992

Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines.

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.

Animals↗