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Biomedical subjects

K Long

Publications and source records attributed to K Long.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of CI-930, a novel phosphodiesterase III inhibitor, on platelet aggregation and arachidonic acid metabolism.

In the platelet-rich plasma of rabbits, 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-5-methyl-3(2H)-pyridazinone (CI-930) inhibited platelet aggregation triggered by AA, U-46619, ADP, collagen and PAF, with the IC50 values of 0.91, 0.73, 2.12, 2.35 and 7.15 mumols/L, respectively. The inhibitory effect of CI-930 on AA-induced aggregation was potentiated by PGE1, an adenylate cyclase activator, and antagonized by SQ-22536, an adenylate cyclase inhibitor. The contents of cAMP in washed rabbit platelets were increased by CI-930 5-50 mumols/L. In the concentration range of 0.5-500 mumols/L, CI-930 reduced the synthesis of TXB2 by either washed rat or rabbit platelets or rat pleural neutrophils. At the same time, CI-930 induced a dose-dependent increase of PGE2, PGF2a, and PGD2 biosynthesis by rat platelets and had no significant influence on the formation of 6-keto-PGF1a by the neutrophils. It is showed that CI-930 is an anti-platelet agent with a wide-spectrum activity and its anti-aggregating action may be exerted by dual mechanisms, both increasing cAMP contents and selectively inhibiting TXA2 synthesis in platelets.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

[Selective inhibition of CI-914 on the production of TXA2 and HHT].

The effects of CI-914, a novel cardiotonic agent, on AA metabolism in rat neutrophils and platelets in vitro were investigated. Using washed rat platelets, the formation of HHT (measured by HPLC), a product of AA metabolism via cyclooxygenase and TXA2 synthetase, was found to be inhibited by the agent in a dose-dependent manner, with IC50 value of 78.6 mumol/L. Only at higher concentration (500 mumol/L) of CI-914, was the production of 12-HETE (measured by HPLC), a lipoxygenase product in platelets, shown to be inhibited. These indicate that CI-914 mainly inhibits the metabolism of AA via cyclooxygenase and TXA2 synthetase rather than via lipoxygenase. In rat platelets and A23187-stimulated pleural neutrophils, CI-914 caused a dose-related decrease of TXA2 production (measured by RIA), with IC50 values of 28.6 and 51.3 mumol/L, respectively. Meanwhile, significant increases of PGE2 synthesis in the platelets and 6-keto-PGF1 alpha synthesis in the pleural neutrophils were observed when CI-914 was preincubated with these cells. It is suggested that CI-914 might selectively inhibit the activity of TXA2 synthetase in rat platelets and pleural neutrophils.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

[Effects of imazodan and dazoxiben on cAMP levels and PGI2 production in cultured bovine aortic endothelial cells].

We have investigated the effects of imazodan, a potent inhibitor of phosphodiesterase III (PDE III) and dazoxiben, a selective inhibitor of thromboxane synthetase on cAMP levels and PGI2 production in cultured bovine aortic endothelial cells by radioimmunoassay. When cultured endothelial cells were incubated with imazodan, intracellular levels of cAMP were increased in a dose-dependent manner. PGI2 production induced by arachidonic acid (AA) was not affected by imazodan 0.1-10 mumol/L. But imazodan 100 mumol/L caused a 35% inhibition of PGI2 production. In the presence of AA, dazoxiben could also elevate intracellular levels of cAMP. Furthermore, dazoxiben 1-10 mumol/L caused a marked increase in PGI2 production, but 1000 mumol/L inhibited PGI2 production.

Animals↗
PubMed1989

[Effect of dazoxiben on cerebrovascular resistance in rabbits].

The effects of dazoxiben, a TXA2 synthetase inhibitor, and indomethacin were compared on cerebrovascular resistance (CVR) and levels of serum TXB2, 6-keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2, respectively) and on protection from acute brain ischaemia caused by ia arachidonic acid (AA) in rabbits. The flow represented the cerebral blood flow (CBF) in two internal jugular arteries were measured with electromagnetic flow meter after occlusion of bilateral vertebral arteries and external jugular arteries. CVR was represented as blood pressure/(CBF.100 g brain). Serum TXB2 and 6-keto-PGF1 alpha levels were determined by radioimmunoassay. The results showed that CVR and BP, EEG, ECG were not affected by treatment with iv dazoxiben 2 or 10 mg/kg. The CVR was enhanced by 35.5 and 49.8% at 30 and 40 min, respectively after iv indomethacin 10 mg/kg. The serum TXB2 level (872 +/- 85) was inhibited to 511 +/- 169 pg/ml (n = 5, P less than 0.05) and 6-keto-PGF1 alpha increased from 668 +/- 309 to 890 +/- 357 pg/ml (n = 5, P less than 0.05) at 30 min after iv 2 mg/kg dazoxiben. However, both TXB2 and 6-keto-PGF1 alpha decreased by 26.4 and 32.7%, respectively at 40 min after iv indomethacin 10 mg/kg. In a model of cerebral ischaemia caused by ia AA in rabbits, the EEG change and enhancement of CVR were antagonized by iv dazoxiben 10 mg/kg completely, but only partly antagonized by indomethacin 10 mg/kg. The results suggest that PGI2 and TXA2 may play a minor role in the regulation of CVR in the physiological condition.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

S-antigen in a hereditary visual cell disease. Immunocytochemical and immunological studies.

S-antigen is a photoreceptor-specific and potentially autoantigenic protein. Using light microscopic immunocytochemistry, the localization of S-antigen was studied in the retinas of normal dogs and Irish setters affected with rod-cone dysplasia, a hereditary retinal degeneration characterized by abnormal cGMP metabolism and arrested outer segment differentiation. Normal and affected dogs were also tested for the presence of humoral and cellular immunity to S-antigen. S-antigen was present in both rods and cones during inner and outer segment differentiation, but there was an apparent loss of immunoreactivity in cones as the retina matured. The developmental appearance and localization of S-antigen in affected retinas was similar to that of normals. S-antigen immunoreactivity decreased during the early stages of rod loss (39-57 days), but was still present in photoreceptor somata in the late stages of retinal degeneration. No significant difference was found between normal and affected setters in humoral immunity to S-antigen, indicating that it probably does not stimulate autoimmunity in red 1. Because normal dog lymphocytes failed to respond when sensitized to bovine S-antigen, cellular immunity to S-antigen in this disease cannot be ruled out.

Animals↗
PubMed1987

Light-stimulated protein movement in rod photoreceptor cells of the rat retina.

We examined the intracellular distribution of three proteins involved in the cyclic GMP cascade of visual transduction; cGMP phosphodiesterase, the alpha-subunit of G-protein and arrestin. In adult rats, light-induced changes in the amounts of G and arrestin in the photoreceptor cell outer segments were observed both by polyacrylamide gel analysis of purified ROS and by immunocytochemical localization on retinal sections. In dark conditions, G was concentrated in the outer segments of photoreceptor cells while in the light G alpha was seen in the inner segments and the outer nuclear layer. Arrestin had the opposite distribution, appearing in the inner segments and outer nuclear layer under dark conditions and in the ROS under light conditions. In contrast, PDE, the enzyme which is activated by G and inhibited by arrestin showed no light-stimulated movement. In both light- and dark-adapted retinas, PDE was localized primarily in the outer segments of the photoreceptor cells.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1987

Verapamil inhibits serotonin uptake of endothelial cells in culture by a mechanism unrelated to Ca2+ channel blockade.

Verapamil inhibited Na+-dependent uptake of serotonin (5-HT) by bovine pulmonary artery endothelial cells in culture both exposed to room air and stimulated by prior exposure to anoxia. The effect of verapamil occurred even in the absence of Ca2+ from the assay medium. Although absence of Ca2+ from the medium moderately reduced 5-HT uptake, stimulation of uptake was nevertheless observed for cells previously exposed to anoxia. Verapamil altered the Km, but not the Vmax, of 5-HT uptake. There was no change in 45Ca2+ uptake or release by cells previously exposed to anoxia as compared to those exposed to room air and verapamil did not influence 45Ca2+ fluxes by either set of cells. It is concluded that verapamil inhibits 5-HT uptake by endothelial cells through a mechanism other than Ca2+ channel blockade; the results are consistent with competitive inhibition of a 5-HT carrier. The stimulatory effect of anoxia on 5-HT uptake does not occur through a change in Ca2+ fluxes.

Animals↗
PubMedDate not supplied

The impact of infant feeding patterns on infection and diarrheal disease due to enterotoxigenic Escherichia coli.

OBJECTIVE: Determine the impact of dietary risk factors on patterns of infection by heat labile toxin-producing Escherichia coli (LT-ETEC). MATERIALS AND METHODS: Ninety-eight infants were followed from birth for one year in Guadalajara, Mexico, beginning in august of 1986. Stool and breast milk samples were collected weekly from infants and their mothers, respectively. Mothers were also interviewed on a weekly basis regarding the health of the infants. Parametric hazard models were fit to durations of different LT-ETEC disease states determined through the analysis of stools. The child's consumption of supplemental foods and liquids as well as specific levels of LT-ETEC-specific breast milk antibodies were included in each model as time-varying covariates. RESULTS: The hazard of LT-ETEC asymptomatic infection increased 400 percent among children who received oats gruel (hazard rate = 4.01; 95% CI 2.77-5.24). The duration of infection was reduced if the child had had a previous LT-ETEC diarrheal episode (2.12; 95% CI 1.74-2.49) but was prolonged if the child consumed herbal teas (0.53; 95% CI 0.27-0.7). Herbal teas and high LT-ETEC-specific breast milk antibody levels each reduced the hazard of symptomatic infection by ninety percent. Symptomatic episodes became asymptomatic more rapidly if a child was given rice water. CONCLUSIONS: Specific weaning foods increase the risk of infection. Breastmilk antibodies and liquid infusions reduce diarrheal disease and infection duration.

Breast Feeding↗