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Biomedical subjects

J M Chapman

Publications and source records attributed to J M Chapman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Subconjunctival gentamicin induction of extraocular toxic muscle myopathy.

Subconjunctival injection of commercially available gentamicin, delivered in one of several protocols, caused an acute toxic reaction myopathy of the extraocular muscles. The response began as a small focal infiltrate of polymorphonuclear leukocytes, and as the lesion progressed it assumed a mononuclear cell predominance accompanied by muscle fiber degeneration. The injection of individual components of the commercial preparation (gentamicin, methylparaben, ethylenediaminetetraacetic acid (EDTA) and sodium bisulfite), each at the same concentration as in the parent solution, gave no response except for gentamicin alone. Gentamicin caused acute toxic myopathy when injected away from the muscles and when given as an isotonic solution in saline compared to the hypotonic commercial solution. Solutions at acidic pH not containing gentamicin did not initiate myopathy. Several factors that have been inferred as participating in the toxic response to gentamicin have been eliminated. Gentamicin alone is responsible for the induction of the extraocular muscle myopathy.

Animals↗
PubMed1992

Corneal endothelial toxicity of dapiprazole hydrochloride.

A new adrenergic antagonist designed for topical use to induce pupillary miosis has been tested for direct toxicity on isolated rabbit corneal endothelium. Dapiprazole hydrochloride was perfused across endothelia in the specular microscope at concentrations from 1.25 micrograms/ml to 1000 micrograms/ml. No toxicity was observed, as determined by corneal thickness determinations over a 3 hour perfusion period, until concentrations greater than 125 micrograms/ml were reached. At 250 micrograms/ml a swelling rate of 17.8 microns/hour occurred, and at 500 micrograms/ml the swelling rate was 17.1 microns/hour; with 1000 micrograms/ml inducing a swelling rate of 23.3 microns/hour. It is evident that the drug concentration that reaches the endothelium after topical application has no toxic effect on the cornea, and that the drug should only be used as directed and not used as an anterior chamber perfusate.

Adrenergic alpha-Antagonists↗
PubMed1991

Effects of thymoxamine on corneal endothelium.

We have investigated the effects of 0.02 and 0.2% thymoxamine hydrochloride on the isolated rabbit corneal endothelium. The corneal swelling rate, measured by specular microscopy, indicated that 0.02% thymoxamine caused a swelling rate equal to controls while a 0.2% concentration caused a significantly increased swelling rate (34.1 vs 10.3 microns/h; P less than 0.05). The data suggests that the maximum recommended intracameral concentration of thymoxamine be 0.02% in order to allow a 10-fold safety factor for the corneal endothelium.

Animals↗
PubMed1990

Interactions of benzalkonium chloride with soft and hard contact lenses.

We measured the uptake and washout of benzalkonium chloride, using radioactive tracer, by representative hard and soft contact lenses. Uptake by soft contact lenses after 7 days of continuous exposure is high (30 to 56 micrograms/mg of lens weight), with a low percentage of washout in 24 hours (between 0.2% and 1.5% of total uptake). High-water content lenses absorb greater quantities of benzalkonium than do low-water content lenses. Hard lenses take up a much smaller quantity of benzalkonium but release between 30% and 60% of total uptake during washout for 24 hours. Fluorosilicone-acrylate polymer lenses adsorb and release the most preservative, while polymethylmethacrylate lenses (Paragon Optical Inc, Mesa, Ariz) adsorb and release the least. The released benzalkonium from either soft or hard lenses is of a sufficient concentration to be at or above the upper limits of safety.

Benzalkonium Compounds↗
PubMed1990

Structure activity relationships of imido N-alkyl semicarbazones, thiosemicarbazones and acethydrazones as hypolipidemic agents in rodents.

A series of nitrogen substituted N-butan-3-one derivatives of cyclic imides (phthalimide, substituted phthalimide, o-benzosulfimide, 1,8-naphthalimide, 2,3-dihydrophthalazine-1,4-dione and diphenimide) and their semicarbazone, thiosemicarbazone and acethydrazone derivatives were investigated for hypolipidemic activity in rodents. These compounds were generally potent hypolipidemic agents, lowering serum cholesterol levels on an average of 37% and serum triglyceride levels on an average of 29% after 16 days dosing at 20 mg/kg day intraperitoneally (I.P.) in mice. Several analogs, most notably the semicarbazone and acethydrazone derivatives of 1-N-(1,8-naphthalimido)-butan-3-one, demonstrated improved hypocholesterolemic activity relative to their ketone precursors. Similarly, the acethydrazone derivatives generally resulted in improved hypotriglyceridemic activity in each series of 2-(3-oxobutyl)-2,3-dihydrophthalazone-1,4-dione analogs tested. The thiosemicarbazones in mice generally resulted in a loss in hypolipidemic activity. Select compounds, 1-N-3-methylphthalimido butan-3-semicarbazone (Ig) and 1-(4-methoxyphthalazine-1(2H)-one)yl butan-3(N-acetyl)hydrazone (IVg), at 10 mg/kg/day orally administered to rats demonstrated potent hypolipidemic activity after 14 days. These compounds lowered liver, small intestine mucosa and aorta wall tissue lipids, e.g. cholesterol and triglycerides, and raised fecal excretion of cholesterol moderately and of triglyceride significantly. Rat serum lipoprotein fractions after treatment for 14 days showed that the two agents lowered VLDL cholesterol and raised HDL cholesterol content.

Animals↗
PubMed1990

Affinity purification of retinoic acid-binding proteins using immobilized 4-(2-hydroxyethoxy)retinoic acid.

An affinity chromatographic matrix that purifies cellular retinoic acid-binding protein to near homogeneity from rat testes cytosol has been developed. The three-step procedure includes an acid precipitation, a batch treatment with CM Bio-Gel, and affinity chromatography on 4-(2-hydroxyethoxy)retinoic acid coupled to epoxy-activated Sepharose 6B. The binding protein was purified approximately 8500-fold based on total soluble testicular protein and with a recovery in excess of 80%. In addition, further enhancement of the purity of the protein can be attained by size-exclusion HPLC to increase purification to 21,000-fold. The recovered protein has an apparent M(r) 14,300 as determined by size-exclusion HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein is isolated in the apo-form and retains its ability to bind retinoic acid as evidenced by the binding of [3H]retinoic acid. An apparent retinoic acid-binding protein of M(r) 18,000 has also been isolated from rat testes nuclei by the affinity chromatography step. The affinity phase has been used for 6 months without any detectable loss in its ability to purify cellular retinoic acid-binding protein.

Animals↗
PubMed1990

The anti-inflammatory activity of 5H-dibenz[c,e]azepine-5,7(6H)dione, 6,7-dihydro-5H-dibenz[c,e]azepine, N-benzoylbenzamide and 1H-benz[d,e]isoquinoline-1,3(2H)dione derivatives in rodents.

A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N-benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N-butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline-1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations.

Animals↗
PubMed1990

Morphologic and physiologic effects of thymoxamine on corneal endothelium and ciliary processes.

Either 0.2 or 0.02% thymoxamine hydrochloride was perfused across the endothelium of isolated rabbit corneas in a specular microscope. Treated corneas did not swell, compared to controls, when perfused with 0.02% thymoxamine, but swelled at 34 microns/hr after 0.2% thymoxamine compared to 10 microns/hr of controls. Morphologically, 0.2% thymoxamine caused many intracellular vacuoles, with far fewer changes after 0.02%. Replacement of the aqueous humor with 0.02% thymoxamine caused no effect on either the corneal endothelium or ciliary process, whereas 0.2% caused small, but significant, changes in both tissues.

Animals↗
PubMed1989

Cytotoxic effects of methionine alkyl esters and amides in normal and neoplastic cell lines.

Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma. Cytotoxicity, as determined by [3H]thymidine incorporation, was found to be directly proportional to alkyl chain length and surface tension lowering activity. L-Methionine decyl and dodecyl ester hydrochlorides possessed optimum cytotoxic activity (IC50 = 29, 28 microM) which was not reversible by the addition of L-methionine. Surface tension of a 50 microM solution of the decyl and dodecyl ester hydrochlorides were 35.4 and 32.7 dyn/cm, respectively. The corresponding decyl and dodecyl ester tosylates and amide hydrochlorides were less active. The N-t-butoxycarbonyl analogues were essentially inactive, demonstrating the necessity of an unsubstituted and/or potentially cationic amino group. Methionine dependence characteristics and cytotoxicity were also determined for three human (IMR-90, LX-1, MCF7) and four additional murine (L1210, L5178Y, 3T3, SV-T2) cell lines. The human cell lines Meth A, LX-1, and SV-T2 were found to be methionine independent. The LX-1 tumor cell line and the SV-T2 transformed line exhibited two to four times more sensitivity to the cytotoxic and cytolytic properties of the decyl and dodecyl ester hydrochlorides than their normal counterparts. The dodecyl amide hydrochloride derivative demonstrated enhanced cytotoxic activity in vivo relative to the corresponding ester, possibly due to decreased metabolic hydrolysis.

Animals↗
PubMed1989

Hypolipidemic activity of cyclic imido alkyl ethers, thioethers, sulfoxides, and sulfones.

N-Substituted alkyl ethers, thioethers, sulfoxides, and sulfones of cyclic imides (e.g., phthalimide, saccharin, 1,8-naphthalimide, succinimide, and 2,3-dihydrophthalazine-1,4-dione) were shown to have potent hypolipidemic activity at doses of 10 and 20 mg/kg/d in rodents. These N-substitutions afforded no improvement over other known N-substitutions (e.g., butyl, 3-butanone, or the propionic acid derivatives of phthalimide, saccharin, and 2,3-dihydrophthalazine-1,4-dione) compared with the respective parent compounds. However, 2-(methoxyethyl)-1H-benz[de]isoquinoline-1,3-(2H)dione (3a), 2-[2-methylsulfinyl]ethyl-1H-benz[de]isoquinoline-1,3-(2H)dione (3c), 1-(2-methylsulfinyl)-2,5-pyrrolidenedione (4c), and 1-(2-methoxyethyl-2,5-pyrrolidenedione (4a) significantly improved activity compared with parent compounds, as well as previously reported N-substituted analogues, reducing serum cholesterol levels and serum triglyceride levels by 40%. The thioether of succinimide afforded a 54% reduction of serum cholesterol and a 41% reduction of serum triglyceride levels in mice after 16 d. The alkyl thioethers of 1,8-naphthalimide and succinimide significantly lowered cholesterol levels in serum VLDL and LDL, while the alkyl thioethers of succinimide elevated HDL cholesterol content. Tissue lipids were reduced in the liver and aorta by these selected derivatives. The activities of regulatory enzymes in de novo synthesis of hepatic cholesterol and triglyceride were inhibited by the selected 1,8-naphthalimide derivatives. In situ cholesterol and cholic acid reabsorption from intestines were suppressed by the presence of the agents.

Animals↗
PubMed1989

Affinity chromatographic purification of serum retinol-binding protein using 4-substituted aminoretinoids.

Retinol-binding protein has been purified from rabbit serum by a new affinity chromatographic phase. Human retinol-binding protein has been shown to bind with vitamin A derivatives and certain other terpenoids. Consequently, this affinity method is based upon the ability of the protein to reversibly bind to beta-ionone and employs a derivatized affinity ligand while preserving the integrity of the beta-ionone molecule via substitution of the allylic 4-position. Purification is relatively simple when compared with other known methods and the yield from serum is similar to other schemes. The protein is obtained in the apo-form and retains the ability of the native protein to bind retinol.

Animals↗
PubMed1989

The hypolipidemic activity of 1-N-3-methylphthalimido-butan-3-semicarbazone in rodents.

1-N-(3-Methylphthalimido)butan-3-one semicarbazone demonstrated potent hypolipidemic activity normal rats and mice and hyperlipidemic diet-induced mice. The compound decreased tissue lip levels and increased the fecal excretion of cholesterol and triglycerides. After 2 weeks of administration, serum lipoprotein levels were modulated so that very low-density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol concentrations were reduced and high-density lipoproteins (HDL) cholesterol concentrations were elevated to levels unprecedented by the cyclic imide derivatives previously tested. The VLDL triglyceride content was also reduced. Hepatic in vitro enzymatic studies demonstrated that the compound suppressed the activity of enzymes in the early synthesis of fatty acids and cholesterol and the regulatory enzymes for the de novo synthesis of triglycerides.

Animals↗
PubMed1989

A comparison of the cholinergic activity of selected H2-antagonists and sulfoxide metabolites.

Famotidine and selected H2-antagonists were evaluated with respect to toxicity and selected pharmacological activities. When administered intraperitoneally to mice at a dose equivalent to 10 times their respective H2-antagonist ED50 values, no deaths were observed. Similarly, no alteration in brain ACh concentrations or overt pharmacological effects were noted. However, at 400 mg/kg, ranitidine produced 89% lethality, followed by cimetidine (11%) and famotidine. Only cimetidine and famotidine at this dose significantly elevated brain acetylcholine levels. These results do not correlate with the in vitro data, where ORF-17578 and ranitidine were the most potent entities with respect to acetylcholinesterase inhibition (approximately 1-2 X 10(-6) M), followed by nizatidine greater than cimetidine greater than famotidine. The sulfoxide metabolites of ranitidine and cimetidine were approximately one-tenth as potent as their parent compounds with respect to inhibition of acetylcholinesterase. Direct muscarinic stimulation or potentiation of acetylcholine-induced contraction in ileal tissue was not observed for any of the H2-antagonists.

Acetylcholine↗
PubMed1989

Alfentanil used to supplement propofol infusions for oesophagoscopy and bronchoscopy.

This randomised double-blinded study compared the cardiovascular stability and rate of recovery when propofol infusions with or without alfentanil were used to provide anaesthesia for rigid oesophagoscopy and (or) bronchoscopy. Forty-six patients were allocated randomly to receive either alfentanil 10 micrograms/kg or saline just before a rapid sequence induction with propofol. Suxamethonium 1 mg/kg was given and infusions of suxamethonium 10 mg/minute and propofol (10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for 10 minutes and then 6 mg/kg/hour thereafter) were started. There were 23 patients in each group with no significant demographic differences between the groups. A significantly mean lower induction dose of propofol was needed in the alfentanil group (1.7 mg/kg compared to 2.2 mg/kg). Cardiovascular measurements were made on the ward pre-operatively, just before induction, just after induction, just after intubation, and at 3-minute intervals thereafter. Arterial pressure was significantly lower during the procedure in the patients who received alfentanil and there was a significant incidence of hypotension. There was no significant difference between the groups in respect of heart rate, with a significant increase in both groups just after intubation compared to the baseline values. Recovery from anaesthesia was assessed using the critical flicker fusion threshold. No differences were found between the groups and patients in both groups had returned to baseline values by 60 minutes. No patient had any recall of intra-operative events, and there were no other adverse effects of any significance.

Adjuvants, Anesthesia↗
PubMed1989

Preservative effects on the healing rate of rabbit corneal epithelium.

Benzalkonium chloride (BAK), sodium lauryl sulfate (SLS), chlorhexidine digluconate, thimerosal and polyaminopropyl biguanide were tested for their effects on the rate of corneal epithelial regrowth after mechanical lesions, and BAK and SLS after heptanol-generated lesions in rabbit corneas. Only 1.3% SLS reduced the rate of epithelial healing after three times a day drop application as determined using planar measures of epithelial regrowth. SLS, a common ingredient in soups and shampoos, should be used carefully where a lesion or wound is present in the corneal epithelium.

Animals↗
PubMed1987

Effect of oral or intravenous pentoxifylline on ocular and optic nerve blood flow.

The effect of oral and intravenous pentoxifylline administration on ocular and optic nerve blood flow was studied in phakic rabbit eyes using a radioactive microsphere (85Sr) technique. Blood flow measurements were performed either 30 min after intravenous injection of 20 mg of pentoxifylline, or 2-3 h after oral administration of 20 mg of pentoxifylline. Blood flow measurements were determined for the iris, scraped ciliary processes, choroid, retina, and optic nerve. The only statistically significant difference noted was for blood flow in the optic nerve in the oral- versus intravenous-treated groups. Neither was significantly different from the control group.

Administration, Oral↗