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Biomedical subjects

J Salmon

Publications and source records attributed to J Salmon.

At least 73 records · Page 4Linked to original sources

A small phospholipase inhibitory factor released by cultured cell lines.

Cells of the mouse macrophage-like cell line RAW264 release a dialysable inhibitor of phospholipase activity into their culture medium. This inhibitor can be detected in saline solution, Hanks solution and a variety of tissue culture media in the presence or absence of serum. The inhibitor is stable at 4 degrees C, unaffected by trypsin, nucleases, or boiling, and partially extractable with chloroform/methanol. The release of both arachidonic acid and prostaglandins from mouse macrophages or human monocytes is inhibited by this material. A variety of other cell types release the inhibitor, which is effective against stimulation of arachidonic acid release from cultured macrophages by zymosan, serum, immune complexes and the calcium ionophore A23187.

Animals↗

Macrophage Fc gamma 2b receptor expression and receptor-mediated phospholipase activity: regulation by endogenous eicosanoids.

The expression of Fc gamma 2b receptors and receptor-mediated arachidonic acid metabolism by murine peritoneal macrophages was examined in vitro. The expression of Fc gamma 2b receptors was found to increase progressively with time in culture and this increase was dependent on protein synthesis and glycosylation. The increase in Fc gamma 2b receptor expression was inhibited by hydrocortisone and by BW755C, an inhibitor of both the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism. Inhibition by BW755C was found to be reversed in the presence of exogenous leukotriene D4. In contrast, selective inhibition of the cyclo-oxygenase pathway by indomethacin enhanced the increase in receptor expression. This enhancement was only partially reversed by exogenous prostaglandin (PG)E2. Interaction of the Fc gamma 2b receptor with ligand in the form of erythrocytes specifically sensitized with IgG2b resulted in the release and subsequent metabolism of arachidonic acid. PGE2 was found to be the principal product. Occupation of the Fc gamma 2a receptor did not result in arachidonic acid release. Down regulation of Fc gamma 2b receptor expression produced a commensurate reduction in receptor-mediated phospholipase activity measured by arachidonic acid release. Macrophages cultured for 24 h in the presence of fetal calf serum without additional stimuli produced substantial amounts of eicosanoids. PGI2 was the principal product. Taken together these data demonstrate a potential feedback regulation of receptor-triggered arachidonic acid metabolism by eicosanoids acting at the level of Fc gamma 2b receptor expression.

Animals↗

Heterocyclic analogues of chlorcyclizine with potent hypolipidemic activity.

A series of [alpha-(heterocyclyl)benzyl]piperazines was synthesized and their effect of reducing serum cholesterol and triglyceride levels in the rat was evaluated. A systematic exploration of the structure-activity relationships led to the synthesis of (R,S)-(3,5-dimethylisoxazol-4-yl)[4-(1-methylethyl)phenyl] (4-methylpiperazin-1-yl)methane dihydrochloride (M&B 31 426), which had potent activity in lowering serum lipid levels at a daily oral dose of 2 mg/kg and was 100 times more potent than clofibrate.

Animals↗

Long-term follow-up of intraocular lens implants: the first 127 compared with the latest 100 of the same style in a span of 9 years.

The long-term follow up of the first 127 patients (127 eyes) treated by one surgeon with cataract extraction and Federov I lens implantation is reported. The proportion of patients achieving visual acuity of 6/12 or better had decreased since the one year follow-up. Corneal oedema was the most serious long-term complication. This group of patients is compared with the latest 100 patients (100 eyes) operated on by the same surgeon using the same type of implant. There was a reduction of some operative complications, and improvement in surgical techniques had resulted in a lower sample endothelial cell loss at one month.

Aged↗

Appearance of specific antigenic proteins in the maturing sexual organs of Sinapis flowers.

Three proteins specific to the flowering state were found in Sinapis by immunological techniques. Two of these are specific to the stamen and one to the pistil. By the use of a histoimmunofluorescence technique their localization in the developing flower primordia and in the apex was examined during the transition to flowering. These proteins are not detected in the apex at evocation. They all appear at a relatively late stage of stamen or pistil maturation. The stamen proteins are localized in both the intine and exine layers of pollen grains in stamens 2-3 mm long; at anthesis they are essentially in the exine. The pistil protein is found in the stigma and in the transmitting tissue of the style. All these proteins contain sugar residues. A possible implication of these proteins in the process of male-female recognition is discussed.

Antigens↗

Normal speech for patients with laryngeal webs: an achievable goal.

Normal speech as well as an improved airway is now an achievable goal in the treatment of laryngeal webs. Seven acquired webs and 3 congenital webs were seen at the North Carolina Baptist Hospital/Bowman Gray School of Medicine. The speech of 6 patients was tested preoperatively and again postoperatively: speech was considered normal postoperatively in 5 patients without the need for speech therapy; normal in the sixth patient after 6 sessions of speech therapy. The authors' preferred method of treatment is development of an endolaryngeal mucosal flap with a variable beam CO2 laser under operating microscopic control.

Adolescent↗

Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers.

The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml-1 (range 3.6 to 15.5 ng ml-1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean +/- SD half-life of 7.06 +/- 1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml-1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.

Adult↗

Pharmacokinetics and metabolism of moxestrol in humans.

Moxestrol, the 11 beta-methoxy derivative of ethynyl estradiol and a highly potent estrogen, is rapidly distributed in the body (AIVD = 148.6 +/- 19.71, MCR = 79.9 +/- 10.5 1/h) after i.v. administration because it is not bound by SBP and has low affinity for albumin. Its oral bioavailability is about 33% after administration of 30 or 100 micrograms to healthy volunteers and slightly lower than that of ethynyl estradiol (50%) due to a "first-pass effect". Moxestrol is rapidly metabolized by the liver as shown by the much increased bioavailability (60.5%) in patients with impaired liver function. The radioimmunoassay for moxestrol measures plasma moxestrol levels ranging from 100 pg/ml (maximum) to 10 pg/ml (24 h value) after treatment with a 100 micrograms commercial formulation (Surestryl). Moxestrol metabolism was studied on urine which contained 28% of administered radioactivity after i.v. or oral administration. Hydroxylation was the main transformation pathway as for ethynyl estradiol. Moxestrol yielded metabolites hydroxylated (or methoxylated) at C-2, C-15 and C-16, but not at C-6, and also gave rise to D-homo derivatives. The main difference between moxestrol and ethynyl estradiol lies in the relative importance of these pathways. The presence of the ethynyl group of ethynyl estradiol impedes attack at C-16 and hydroxylation at C-2 to form catechol estrogens becomes a major pathway, whereas the 11 beta-methoxy group of moxestrol impedes hydroxylation at C-2 and ring D hydroxylated products of moxestrol are formed. The low amount of catechol estrogens obtained with moxestrol compared to ethynyl estradiol could have important physiological implications in the human.

Administration, Oral↗

Pharmacokinetics and metabolism of moxestrol in animals--rat, dog and monkey.

The pharmacokinetics and metabolism of moxestrol have been compared in the rat, dog and monkey (rhesus and baboon) and, in some instances, confronted with data simultaneously obtained for ethynl estradiol and previously obtained in humans. The apparent initial volume of distribution (AIVD) of total radioactivity after i.v. administration was of the order of body volume in all species under study; the AIVD of intact moxestrol was even higher. This is in agreement with moxestrol's low binding to specific and non-specific plasma proteins. The half-life of total radioactivity elimination was 14-18 h in the rat and rhesus monkey, but longer (43 and 78 h, i.v. and oral respectively) in the baboon. In the dog, the elimination phase could not be distinguished from the distribution phase and had a half-life of 2 h. The half-life of unchanged moxestrol elimination was shorter and very similar in the rhesus, baboon and human (6.6, 7.5 and 8.2 h respectively) and only 1.4 h in the dog. Regardless of the route of administration or the species under study, the clearance and elimination rate of unchanged moxestrol were higher than of total radioactivity implying that metabolites and/or conjugation products were eliminated more slowly than intact product from plasma. Orally administered moxestrol was rapidly absorbed in all species. Since clearance of total radioactivity and of moxestrol was faster after i.v. than oral administration, but the radioactivity levels excreted in the urine were identical for the two routes, a significant first-pass-effect probably occurred in the liver. Radioactivity distribution in tissues was examined in the rat. Total radioactivity was higher 24 h after administration of labelled moxestrol than of labelled ethynyl estradiol in endocrine tissues; it was equivalent or less in the other tissues. For all tissues, the elimination rate of moxestrol was greater than, or equal to, that of ethynyl estradiol. In dog urine, the only product identified was moxestrol; in rhesus or baboon monkey urine, the principal metabolites were catechol estrogens, which were also present in appreciable amount in rat bile (as methyl ethers) but were minor metabolites in human urine. Hydroxylation in position 16 occurred in rats and humans only, in position 15 alpha in humans and, to a much lesser extent, in rats and monkeys. Thus, the metabolic profile of moxestrol in rats most closely resembles that in humans.

Animals↗

Quantification of the C3 breakdown product C3d by rocket immunoelectrophoresis.

The levels of the C3 breakdown product C3d were measured in plasma, serum, and synovial fluid by the technique of rocket immunoelectrophoresis. Serum and plasma from 22 healthy donors, 4 patients with rheumatoid arthritis, 1 patient with systemic lupus erythematosus, and 1 patient with cryoglobulinemia were used. The synovial fluid was studied in 3 other patients with rheumatoid arthritis. Normal values for the 22 healthy donors in plasma were within a narrow range of 3.25--5.75% as compared to the standard pool that was prepared. Storage of plasma to -80 degrees C during 7--15 days did not modify the results of the test. Significant differences in C3d values were observed between serum and EDTA plasma samples. Patients with immunological diseases showed higher values of C3d in the samples (from 5 to 30% of activity as compared to the standard pool). Measurement of C3d by rocket immunoelectrophoresis showed to be an easy, satisfactory and reliable procedure able to be incorporated to routine immunological evaluations.

Arthritis, Rheumatoid↗

[Platelets, lysosomal enzymes and anaphylactic shock in the rat].

1. Rat serum levels in beta-glucuronidase and beta-galactosidase are higher than plasma levels. Rat platelets release these lysosomial enzymes during blood coagulation in vitro. 2. After anaphylactic shock, in the sensitized rat, there is no increase in beta-galactosidase and beta-glucuronidase plasma levels. The tissues of the sensitized rat do not release these enzymes during the antigen-antibody reaction. The blood platelet level is diminished after anaphylactic shock and the serum levels of the lysosomial enzymes are decreased. 3. In thrombopenic rat, anaphylactic shock is identical as in control animals. Rat platelets do not play a significant role in the anaphylactic shock.

Anaphylaxis↗

Acute parotitis and hyperamylasemia following whole-brain radiation therapy.

Parotitis, an infrequent, previously unreported complication of whole-brain radiation therapy, was observed in 4 patients. The acute symptoms, which include fever, dry mouth, pain, swelling, and tenderness, are accompanied by hyperamylasemia. Among 10 patients receiving whole-brain irradiation, 8 had serum amylase elevations without symptoms. Both acute parotitis and asymptomatic hyperamylasemia result from irradiation of the parotid glands.

Adult↗