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At least 703 records · Page 39Linked to original sources
PubMed1990

Effects of platelet-activating factor on rat mesenteric microcirculation.

The actions of platelet-activating factor (PAF) on rat mesenteric microcirculation were studied by laser Doppler microscopy in vivo. PAF 0.2 -0.6 micrograms/kg iv produced a dose-related decrease in the blood flow velocity and an increase in the diameters of the mesenteric arterioles and venules. These responses were completely reversed by pretreatment with PAF receptor antagonist SRI 63441. The results suggest that PAF may be a mediator of microcirculatory disturbances in the disease conditions associated with excessive PAF release.

Animals↗
PubMed1990

Interaction of DNA intercalator 3-nitrobenzothiazolo (3,2-a)quinolinium with DNA topoisomerases: a possible-mechanism for its biological activity.

There is multiple evidence linking the inhibition of DNA topoisomerases I and II with the cytotoxic effects of antitumor drugs such as camptothecin and the DNA intercalators, 4-(9-acridinylamino)methanesulfon-m-anisidine) (mAMSA) and Adriamycin. We have assessed the effect of the DNA intercalator 3-nitrobenzothiazolo(3,2-a)quinolinium (NBQ) on the DNA topoisomerase I and II activities. NBQ has no effect on the activity of purified topoisomerase I, whereas it induced purified topoisomerase II binding to DNA without inducing DNA scission. Above 30 microM, NBQ stimulated formation of double- and single-strand breaks mediated by topoisomerase II in plasmid DNA. Using the alkaline elution technique we determined that NBQ induced single-strand and DNA-protein-associated breaks in the human promyelocytic leukemia cell line HL-60. At sublethal concentrations (less than or equal to 1 microM), NBQ induce HL-60 cells to differentiate. Topoisomerase II-mediated DNA cleavage induced by mAMSA was substantially reduced in NBQ-differentiated cells. Our data suggest that topoisomerase II could play a major role in the biological activity of NBQ in vivo.

Cell Differentiation↗
PubMed1990

Reconstitution of the uncoupling protein of brown adipose tissue mitochondria. Demonstration of GDP-sensitive halide anion uniport.

The fluorescent anion indicator 6-methoxy-N-(3-sulfopropyl)quinolinium was trapped in proteoliposomes reconstituted with purified 32-kDa uncoupling protein and used to detect GDP-sensitive uniports of Cl-, Br-, and I-. Transport of these halide anions was rapid and potential-dependent. F- and nitrate were found to inhibit Cl- uptake competitively, suggesting that these anions are also substrates for transport. This preparation also exhibited H+(OH-) transport, showing that the reconstituted uncoupling protein possesses both halide and H+ transport functions, as is observed in intact brown adipose tissue mitochondria. Cl- transport was inhibited to the residual level observed in liposomes without protein when GDP was present on both sides of the membrane. Cl- transport was inhibited by about 50% when GDP was present only on one side of the membrane. We infer that uncoupling protein reconstitutes into proteoliposomes with a 1:1 ratio of sidedness orientation. The Km values for Cl- uniport were 100 and 65 mM, respectively, in GDP-loaded and non-GDP-loaded vesicles. Participation of the inner membrane anion channel in the observed transport is rendered unlikely by the fact that this carrier is insensitive to GDP. A variety of additional experiments probing for inner membrane anion channel yielded uniformly negative results, confirming the absence of contamination by this protein. Our results therefore demonstrate that the uncoupling protein mediates anion translocation, a function previously reported as lacking in the reconstituted system.

Adipose Tissue, Brown↗
PubMed1990

Improved preservation of the rat liver for orthotopic liver transplantation: use of University of Wisconsin-lactobionate solution and retrograde reflushing.

This study investigated cold preservation and reflushing before orthotopic liver transplantation by examining (1) new University of Wisconsin solution (UW) versus Euro-Collins solution (EC), (2) retrograde reflushing (RR) versus antegrade reflushing (AR), and (3) the addition of a platelet-activating inhibitor (PAF), superoxide disumatase (SOD), or SOD + catalase to UW. Syngeneic, male Lewis rats (200 to 400 gm) were used. Preservation for 9, 12, 18, or 24 hours in UW or EC with RR (through the inferior vena cava) was used. The 9- and 12-hour groups experienced a significant decrease in the weight of the grafts preserved in UW. The 3-week survival rate after 9 hours of preservation (n = 6) in UW was 66%, and the survival rate with EC was 0% (p less than 0.025). After 12 hours of preservation, recipient survival rate was 70% (n = 10) with UW versus 0% (n = 4) with EC (p less than 0.025). RR of the graft with cold lactated Ringer's solution immediately before reimplantation significantly improved 3-week survival in the 12-hour group to the level of the control group (no preservation time, 69%). Preservation for 12 hours in UW followed by AR yielded a 3-week survival of 14%; 3-week survival for the RR group was 70% (p less than 0.025). Furthermore, RR allowed a 3-week survival of 33% and 20% after 18 and 24 hours of UW preservation, respectively. In the 24-hour RR/UW group, donor pretreatment with SRI 63-441 (20 mg/kg, intravenously) and recipient treatment with SOD (15 mg/kg, intravenously) or SOD + catalase (15 mg/kg and 5000 units/kg, intravenously) produced a 3-week survival comparable to preservation in UW followed by RR alone. These studies show that UW is a profound improvement over EC for cold preservation of liver and that the new application of RR to rat orthotopic liver transplantation improves survival. However, the addition of free-radical scavengers or PAF does not improve organ function or recipient survival in this model.

Adenosine↗
PubMed1990

Comparison of the efficacy of a phenothiazine and a bisquinaldinium calmodulin antagonist against multidrug-resistant P388 cell lines.

Dequalinium belongs to a group of cationic lipophilic drugs believed to be selectively cytotoxic to malignant cells of epithelial origin by virtue of their accumulation in mitochondria. In addition, they are potent inhibitors of calmodulin and, therefore, might sensitize multidrug-resistant cells to chemotherapeutic agents. We compared the responsiveness of multidrug-resistant cells to the effect of dequalinium with that to trifluoperazine, a potent phenothiazine inhibitor of calmodulin. In addition, we studied the effect of these drugs on the responsiveness of multidrug-resistant cell lines to doxorubicin. The effect of drugs on P388 murine leukemic cells was determined by cell counting, [3H]thymidine incorporation into DNA, or soft agar cloning. Drug accumulation was measured by fluorescence spectrophotometry. We found that multidrug-resistant lines were less sensitive than parental cell lines to the intrinsic growth inhibitory effects of dequalinium (IC50, 4.4 versus 0.3 microM in multidrug-resistant and sensitive P388 cells, respectively), whereas they were equally sensitive as the parental line to the effects of trifluoperazine. Following a 3-h exposure of P388/doxorubicin-resistant cells to 0-100 microM doxorubicin with or without either 10 microM dequalinium or 10 microM trifluoperazine, the latter increased the sensitivity to doxorubicin whereas the former had little effect (IC50 values were doxorubicin, 30 microM; doxorubicin plus dequalinium, 25 microM; doxorubicin plus trifluoperazine, 4 microM). Calmodulin prepared from resistant cells were equally sensitive to inhibition by dequalinium and trifluoperazine. P388/doxorubicin-resistant cells accumulated 4.5-fold less dequalinium than P388 cells whereas trifluoperazine was accumulated equally in both. The addition of 4 microM trifluoperazine to resistant cells exposed to 0-100 microM dequalinium completely reversed the alteration in accumulation and resistance to the dequalinium. These studies demonstrate that certain multidrug-resistant lines are cross-resistant to dequalinium and that sensitivity can be completely restored by nontoxic concentrations of trifluoperazine. The resistance appears to be due to changes in drug accumulation and not to be related to an altered sensitivity of calmodulin.

Animals↗
PubMed1990

Effects of in vivo 'priming' on endotoxin-induced hypotension and tissue injury. The role of PAF and tumor necrosis factor.

Exogenously administered tumor necrosis factor-alpha (TNF) and bacterial endotoxin (LPS) induce shock and tissue injury. Here, the authors studied the effect of endogenous TNF on LPS-induced hypotension and tissue injury and investigated the role of PAF in these responses. Rats were primed with intraperitoneal injection of zymosan 24 hours before, or Bacillus Calmette-Guérin (BCG) 12 to 15 days before intravenous injection of low dose (0.5 mg/kg) LPS. It was found that nonprimed animals showed mild hypotension and moderate leukopenia in response to LPS. In contrast, zymosanprimed rats developed shock and marked leukopenia, and more severe bowel injury than nonprimed rats. The authors then showed that, following LPS injection, zymosan-primed animals had higher TNF and platelet-activating factor (PAF) levels than nonprimed rats. Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury. Interestingly, BCG-primed rats did not show aggravation of LPS-induced hypotension. Only TNF (but not PAF) level in these animals was increased. Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension. However, most of the BCG-primed animals showed tissue injury, which could be prevented by pretreatment with PAF antagonist. The authors discuss the possible mechanisms of this discrepancy between systemic and local responses in BCG-primed animals.

Animals↗
PubMedDate not supplied

[Antimicrobial characteristics of a tincture of dequalinium chloride].

Dequalinium is a quaternary ammonium salt. From about 30 years Dequalinium (D.C.) was used in the treatment of the initial respiratory organs infections. It can be given orally and topically yet it cannot be given systemically cause its probable systemic toxicity. D.C. has a wide range of antimicrobial activity that is extended to Gram positive, Gram negative bacteria, protozoa and yeast. Its mechanism of action is directed to the cytoplasmatic membrane where D.C. caused its damage and consequently release of cellular components. Our study has been evaluated the antimicrobial activity of D.C. both as commercial product that pure substance. We tested 27 Gram positive bacteria, 49 Gram negative bacteria, 83 strains of fungi, we also tested the antimicrobial activity of D.C. commercial product and pure substance against 8 strains of protozoa; Trichomonas vaginalis. The antimicrobial activity was estimated in some experimental conditions, (cultural and no cultural conditions); in these experiments we can observed that the commercial product presents higher activity than pure substance. In cultural condition commercial product presents antimicrobial activity against Gram positive and negative bacteria and yeast; its interesting to evaluate that bacteria, that are resistant to the common antimicrobial agents were inhibited by D.C. tinture and pure substances. Our data exhibit that serum didn't interfere until the 2% concentration with the antimicrobial activity of D.C., moreover this antimicrobial activity is not influenced by the inoculum size until 10(5) cell/ml. D.C. presents higher activity at alkaline pH than acid pH but strains of C. albicans were killed by D.C. at acid pH. In no cultural conditions D.C. has demonstrated a rapid antimicrobial activity in short contact time (15 minute); the cells of some microorganisms were killed in 60 minutes. Against mycelial form, the commercial product demonstrates good activity higher than pure substance. The activity of D.C. against the formation of germ-tube from blastospores of C. albicans in N-acetyl-glucosamine solution (no culture medium) was markedly high; this is very important because in C. albicans the germ-tube production and yeast-mycelial conversion are prominent for pathogenicity and resistance to host defences. Our data demonstrate the good activity of D.C. against Trichomonas vaginalis; we can also observed that the antimicrobial activity of commercial product is higher than pure substance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Equine peritoneal macrophage production of thromboxane and prostacyclin in response to platelet activating factor and its receptor antagonist SRI 63-441.

The formation of eicosanoids may be a primary route through which platelet activating factor (PAF) exerts its effects during endotoxemia. Since endotoxemia is a common cause of death in horses, a study was conducted to determine whether PAF could stimulate equine macrophage release of thromboxane A2 (TxA2) and prostacyclin (PGI2) and whether a PAF-receptor antagonist would alter macrophage eicosanoid synthesis. Equine peritoneal macrophages were cultured from clinically normal horses and exposed to various concentrations of PAF, the PAF-receptor antagonist SRI 63-441, endotoxin, or a combination of these. The supernatant concentrations of TxB2 and 6-keto-prostaglandin F1 alpha were determined after 6 hr incubation. The media concentration of TxB2 was increased significantly above baseline after treatment of macrophages with PAF (10(-7) to 10(-5) M), and the magnitude was similar to that induced by endotoxin. This TxB2 increase was not prevented by prior treatment of macrophages with SRI 63-441. SRI 63-441 (greater than or equal to 5 x 10(-5) M) significantly enhanced macrophage TxA2 synthesis, as well as its production of PGI2, similar to the effects of endotoxin. Media concentrations of 6-keto-prostaglandin F1 alpha were not increased significantly above baseline after treatment of macrophages with PAF (10(-8) to 10(-5) M). These results suggest that PAF may cause increased TxA2 release during endotoxemia, which may not be preventable by use of the PAF-receptor antagonist SRI-63-441, which is capable of inhibiting PAF-induced aggregation of equine platelets.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Determination of the trypanocidal drugs homidium, isometamidium and quinapyramine in bovine serum or plasma using HPLC.

Sensitive HPLC analytical methods for trypanocidal drugs in serum or plasma have been developed. The methods are suitable for the analysis of drugs that are widely used against animal trypanosomiasis at present, including Homidium bromide (Ethidium, Boots Company Ltd.), Homidium chloride (Novidium, May and Baker Ltd.), Isometamidium chloride (Samorin, May and Baker Ltd.), Quinapyramine chloride (Antrycide, ICI) and Quinapyramine sulphate (Trypacide, May and Baker Ltd.). The detection limits for various drugs range between 3 and 20 ng per ml of serum, when serum volumes up to 10 ml have been processed. These methods provide a significant improvement of sensitivity for Isometamidium over existing analytical procedures and represent new methods for analysis of Homidium and Quinapyramine.

Animals↗
PubMed1989

Effect of in vitro cultivation on the stability of resistance of Trypanosoma brucei brucei to diminazene, isometamidium, quinapyramine, and Mel B.

A Trypanosoma brucei brucei stock resistant to diminazene aceturate, isometamidium chloride, quinapyramine sulfate, and Mel B was grown in vitro and its response to these drugs compared to that of a drug-sensitive trypanosome stock. There was little if any change of drug sensitivity after in vitro propagation as bloodstream forms for 120, 177, and 275 days and after in vitro transformation of bloodstream forms into procyclic, epimastigote, and finally metacyclic forms. Drug resistance was stable during in vitro maintenance in the absence of drugs in both culture systems. The response of resistant and sensitive T. b. brucei to diminazene in vitro correlated with their sensitivity pattern in vivo. Thus, in vitro techniques can be used to study drug resistance in trypanosomes.

Animals↗
PubMed1987

Platelet-activating factor both stimulates and "primes" human polymorphonuclear leukocyte actin filament assembly.

The phospholipid inflammatory mediator, platelet-activating factor (PAF), can stimulate polymorphonuclear leukocyte (PMN) chemotaxis. Conversion of cytoplasmic actin from monomers to filaments is associated with PMN motile functions. Using the fluorescent actin filament stain nitrobenzodiaxole phallicidin, we have investigated PAF's effects on human PMN actin polymerization. Concentrations of PAF between 1 x 10(-11) to 1 x 10(-6) mol/L induced actin filament (F-actin) assembly. An optimal concentration of PAF (1-5 x 10(-8) mol/L) induced a significantly lower rise in relative F-actin content (1.72 +/- 0.07 SEM) than an optimal concentration (5 x 10(-7) mol/L) of the chemotactic peptide FMLP (2.21 +/- 0.06). Unlike FMLP (F-actin content: 1.25 +/- 0.04 at five seconds), PAF stimulation was associated with a delay of more than five seconds (1.04 +/- 0.01 at five seconds) before an increase in F-actin could be detected. F-actin concentration reached maximum levels by 30 to 60 seconds. Prolonged stimulation (20 minutes) with PAF was associated with two phases of polymerization and depolymerization. Like FMLP, the initiation of actin filament assembly by PAF required receptor occupancy, this reaction being totally blocked by the PAF receptor inhibitor, SKI 63-441. As evidenced by the lack of inhibition by nordihydroguaiaretic acid (5 to 20 mumol/L), the production of leukotriene B4 was not required for the PAF-induced changes in F-actin. Like FMLP, PAF's ability to stimulate PMN actin polymerization was inhibited by pertussis toxin (.05 to 2.5 micrograms/mL) but not impaired by the addition of EGTA and/or the calcium ionophore A23187. Preincubation with 1 x 10(-11) to 1 x 10(-8) mol/L PAF for 2 to 60 minutes enhanced the rise in F-actin content induced by low concentrations of FMLP (5 x 10(-12) to 1 x 10(-10) mol/L) indicating that this phospholipid was capable of "priming" the PMN actin polymerization response.

Actin Cytoskeleton↗
PubMed1987

[An evaluation of the antibacterial effectiveness of bisdequalinium acetate and sodium hypochlorite].

The antimicrobial effectiveness of sodium hypochlorite and bis-dequalinium acetate was evaluated in vitro using three different microorganisms. The solutions were prepared in various concentrations and microorganisms were exposed to these solutions for 5, 10, 15 min. then placed into a culture medium, incubated and determined the presence or absence of growth. These results were compared with those obtained with phenol. The following conclusions were drawn from this study: 1. Of the solutions tested Bis-dequalinium acetate was the most effective antimicrobial agent. And 1.25/1000 Bis-dequalinium acetate is appropriate for the clinical use. 2. Sodium Hypochlorite is the least effective compared with Bis-dequalinium acetate and phenol. 2/100 NaOCl is agreeable for the clinical use. 3. Normal saline exhibits no antimicrobial properties.

Bacillus subtilis↗
PubMed1988

The effects of PAF antagonists on ischaemia and reperfusion arrhythmias and ischaemia-induced platelet aggregation.

These studies were performed to investigate a role of PAF in the genesis of life-threatening arrhythmias and platelet aggregation accompanying myocardial ischaemia and reperfusion. Pretreatment with the PAF antagonists SRI 63-441 (10 mgkg-1 iv) and BN 52021 (5 mgkg-1 iv) significantly reduced the number of arrhythmias during a thirty minute coronary artery occlusion period in open-chest anaesthetised greyhounds, particularly ventricular tachycardia. Both drugs also reduce the incidence of ventricular fibrillation resulting from reperfusion of the myocardium. Myocardial ischaemia in control animals resulted in a marked fall in platelet count in blood draining the ischaemic area, which was abolished by both SRI 63-441 and BN 52021. These results suggest a role for PAF in the genesis of ischaemia and reperfusion-induced arrhythmias, possibly by inducing platelet aggregation.

Animals↗