Biomedical subjects

H Salari

Publications and source records attributed to H Salari.

80 records · Page 5Linked to original sources

PubMed1984

Comparative effects of etodolac, indomethacin, and benoxaprofen on icosanoid biosynthesis.

Etodolac (Ultradol) is a new tetrahydropyrano-indole derivative which has shown pronounced analgesic and antiinflammatory properties. Its effects on the different pathways of metabolism of arachidonic acid have been studied and compared to the effects of indomethacin and benoxaprofen. All three drugs tested inhibited the cyclooxygenase activity of the parenchyma as assessed by inhibition of LTB4- and LTD4-induced contraction. However, the activity of human polymorphonuclear leukocyte 5-lipoxygenase and of human platelet 12-lipoxygenase was inhibited only by very high concentrations (1 X 10(-4) M and over) of these compounds, whereas nordihydroguaiaretic acid (NDGA) was active at concentrations 100 times lower. In the Schultz-Dale reaction of the guinea pig trachea, etodolac, benoxaprofen, and indomethacin produced increases of the myotropic contractile activity of the tissues sensitized to ovalbumin. Our results do not lend support to the hypothesis that the mechanism of action of these antiinflammatory drugs is linked to the inhibition of lipoxygenases.

Acetates↗

PubMed1984

Comparative effects of indomethacin, acetylenic acids, 15-HETE, nordihydroguaiaretic acid and BW755C on the metabolism of arachidonic acid in human leukocytes and platelets.

Human leukocytes and platelets were preincubated with inhibitors of the oxidative metabolism of arachidonic acid, viz, indomethacin, BW755C, 5, 8, 11, 14-eicosatetraynoic acid (ETYA), 5, 8, 11-eicosatriynoic acid, 15S-hydroxy-5, 8, 11, 13-(Z, Z, Z, E)-eicosatetraenoic acid (15-HETE) and nordihydroguaiaretic acid (NDGA), prior to stimulation with the ionophore A23187 in the presence or absence of exogenous arachidonic acid. Eleven metabolites of arachidonic acid derived from the cyclooxygenase and the 5-, 12- and 15-lipoxygenases were measured by reversed-phase high pressure liquid chromatography (RP-HPLC). Indomethacin was the best inhibitor of the platelet cyclooxygenase (ID50 less than 10(-7)M) as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT); ETYA was the most potent inhibitor of the 12- and 15-lipoxygenases (ID50 approximately 3 X 10(-7)M) whereas NDGA was the most potent and selective inhibitor of the 5-lipoxygenase (ID50 approximately 3 X 10(-7)M).

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1982

Control mechanisms governing the infectivity of Chlamydia trachomatis for hela cells: modulation by cyclic nucleotides, prostaglandins and calcium.

Chlamydia trachomatis causes common infections of the eyes and genital tract in man. The mechanism by which this obligate intracellular bacterium is taken into epithelial cells is unclear. The results described here support the concept that chlamydial infections of HeLa cells is under bidirectional cyclic nucleotide control, with guanosine 3':5'-cyclic monophosphate (cGMP) acting as a stimulator, and adenosine 3':5'-cyclic monophosphate (cAMP) as an inhibitor. Treatment of the HeLa cells with the divalent cation ionophore A23187, with carbamoylcholine, or with prostaglandins known to increase the concentration of endogenous cGMP, also increased host cell susceptibility to chlamydial infection. Cyclic GMP was only effective if added at or before chlamydial inoculation, suggesting that its main effect was on chlamydial uptake. The stimulatory effect of cGMP, but nt antagonism, by cAMP, was abolished if the cells were first treated with any of four different inhibitors of prostaglandin synthesis, suggesting a critical role for endogenous prostaglandin synthesis. Centrifugation of chlamydiae on to host cells was followed by a rapid increase in the mobility of Ca2+ across the cell membrane. The interrelationships of these observations and the possibility that chlamydiae and other intracellular pathogens might evoke alterations in host cell prostaglandin and cyclic nucleotide concentrations to aid their own uptake are discussed.

Bucladesine↗

PubMed1982

In vitro activity of antibiotics commonly used in the treatment of otitis media against Streptococcus pneumoniae isolates with different susceptibilities to penicillin.

Susceptibilities of 82 clinical isolates of Streptococcus pneumoniae, including 25 from the middle-ear fluid, were evaluated against antibiotics commonly used in the treatment of acute otitis media. Potentially significant resistance occurred in 6% of the isolates to erythromycin and an erythromycin-sulfisoxazole combination. The combination of trimethoprim and sulfamethoxazole was synergistic for 95% of the isolates. Only 2.5% of all of the isolates were resistant to both erythromycin-sulfisoxazole and trimethoprim-sulfamethoxazole. The presently used drug regimens should be effective against the majority of S. pneumoniae isolates in otitis media.

Anti-Bacterial Agents↗

PubMedDate not supplied

1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphocholine inhibits diacylglycerol kinase in WEHI-3B cells.

The effects of 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-16-OCH3-GPC) and its metabolite 1-O-hexadecyl-2-O-methyl-sn-glycerol (AMG) on the activity of diacylglycerol kinase (DGK) in WEHI-3B cells were investigated. Treatment of WEHI-3B cells with 200 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) for 5 min leads to the activation of cytosolic DGK without significant effect on microsomal DGK. When these cells were first exposed to 50 microM ET-16-OCH3-GPC for 30 min prior to activation with TPA, the activity of DGK was inhibited by about 70%, as measured by the ability of enzyme to form [32P]phosphatidic acid ([32P]PA). Addition of either ET-16-OCH3-GPC or AMG to the preparation of enzyme in vitro also inhibited 1,2-dioleoyl-sn-glycerol (DG) phosphorylation in the presence of [gamma-32P]ATP. The IC50 value for inhibition of cytosolic DGK by ET-16-OCH3-GPC and AMG were about 8.5 and 15 microM, respectively. ET-16-OCH3-GPC also inhibited the ability of guanosine 5'-O-(3-thiophosphate) (GTP-gamma S) to activate DGK in vitro. The potency of ET-16-OCH3-GPC at 10 microM in inhibiting DGK was greater than that of sphingosine at 50 microM, but less than that of R59022 (a specific DGK inhibitor) at 10 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

A comparison of the lytic properties of two ether-linked lipids, one with and one without antineoplastic activity.

We have synthesized two ether lipids: 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3(S)-methoxybutanephosphonate (compound 1) with antineoplastic activity and a maltosyl derivative (compound 2) without antineoplastic activity. We have compared the antineoplastic activity of these two compounds against WEHI-3B cells with their ability to disrupt the membranes of erythrocytes or neutrophils. Since ether lipids are highly hydrophobic molecules, it is possible that they may exert their cytotoxic action by inducing the nonspecific perturbation of cellular membranes, causing lysis and cell death. Membrane disruption was monitored by the lysis of cells or the change in erythrocyte membrane microviscocity and compared with the effect of detergents (known nonspecific lytic agents). Both compounds 1 and 2 caused the lysis of erythrocytes and neutrophils. The rate of lysis of erythrocytes was comparable to the rate of change of erythrocyte membrane microviscosity caused by both compounds 1 and 2. Both compounds caused the lysis of erythrocytes via a noncolloid osmotic mechanism that displayed features of the lysis caused by detergents at high concentrations.

Antineoplastic Agents↗

PubMedDate not supplied

Pharmacokinetics of CuDIPS in mice.

Pharmacokinetic evaluation of Cu(II)2(3,5-diisopropylsalicylate)4(H2O)2 (CuDIPS), a copper complex with anticancer activity in mice, showed rapid absorption into the circulation after subcutaneous (SC) injection of a 0.50mumol, 0.75 mumol or 1.0 mumol dose. A direct relationship was observed between peak plasma copper concentration (one or two hours) and dose. Rate of plasma release also appeared to be dose related. The lowest dose of CuDIPS had no effect on plasma zinc levels; higher doses produced significant increases, but only at one hour. Rapid absorption into the blood (apparent peak in concentration, Tmax, at 0.5 hours) was also found in studies to determine distribution of 67Cu after SC injection of 67Cu and 14C double-labeled CuDIPS (50 mumol/kg body weight). Distribution to other tissues and organs occurred less rapidly with apparent peak 67Cu concentrations at three hours after administration in femur (bone marrow) and intestine, and at six hours in spleen and thymus.

Animals↗

PubMedDate not supplied

Disulfiram as a radiation modifier.

The radiation modifying effect and toxicity of tetraethylthiuram disulfide (disulfiram) have been studied. Disulfiram (DSM) inhibits aldehyde dehydrogenase, dopamine-beta-oxygenase, microsomal mixed-function oxidases and cytochrome P-450 enzymes. It is widely used for aversion therapy in alcoholism. Disulfiram also inhibits tumor formation by several known carcinogens. A biphasic toxicity pattern of DSM is reported in the L-929 mouse fibroblast culture system. Disulfiram is 100 percent toxic at 2 X 10(-7) M (0.05 micrograms per ml), 23 percent toxic at 3 X 10(-7) M (0.1 microgram per ml), and 100 percent toxic again at 3.4 X 10(-6) M (1.0 microgram per ml). The pattern is similar to the biphasic toxicity pattern of DMS's major metabolite, sodium diethyldithiocarbamate (DTC). Reports of both radiation protection and radiation enhancement by DTC exist. Previously, a radioprotective effect by 2 X 10(-6) M DTC (dose modifying factor = 1.26) has been demonstrated in the L-929 cell system. To date, no radiation modifying properties of DSM have been reported. Our investigation of DSM as a radiation modifier at 3 X 10(-7) M (0.1 microgram per ml) did not show significant improvement in survival of irradiated cells treated with DSM relative to the irradiated control group, as determined by absence of a difference in the Do of the two groups. Considering DSM's close structural relationship to DTC, it is possible that DSM may exhibit a radioprotective effect when applied in a different concentration than what was used in our research.

Animals↗