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Biomedical subjects

H Chung

Publications and source records attributed to H Chung.

At least 127 records · Page 7Linked to original sources
PubMed1988

BCNU in silicone oil in proliferative vitreoretinopathy: I. Solubility, stability (in vitro and in vivo), and antiproliferative (in vitro) studies.

Various pharmacologic agents have been tried to control proliferative vitreoretinopathy (PVR). However, most are water soluble and cannot be used with silicone oil (SO), a tamponade agent also used in PVR management. We evaluated a lipophilic, antiproliferative drug, BCNU, in regard to its solubility and stability in SO, its release from SO into an aqueous solution, and its effect on cell cultures. BCNU is soluble in SO (peak concentration in micrograms/ml 1020, 750, and 294 at 37 degrees C, 21 degrees C, and 4 degrees C, respectively), and stable (half-life = 6.7 weeks at 37 degrees C, 17.9 weeks at 21 degrees C). At 4 degrees C, no significant decrease in concentration up to eight weeks was noted. BCNU is released from SO to water (partition coefficient = 10.28 +/- 2.16). Its median inhibitory doses (ID50) on bovine retinal pigment epithelial (RPE), rabbit RPE, and subconjunctival fibroblast cells are 13, 1.9, and 15.6 micrograms/ml, respectively. BCNU may be a useful pharmacologic tool to control PVR.

Animals↗
PubMed1987

Analysis of artesunic acid and dihydroqinghaosu in blood by high-performance liquid chromatography with reductive electrochemical detection.

A new high-performance liquid chromatography (HPLC) method using reductive electrochemical detection has been developed for the analysis of the antimalarial drugs artesunic acid (ARTS) and dihydroqinghaosu (DQHS) in blood. Presently, this method has been validated to 4 micrograms/ml for ARTS and 200 ng/ml for DQHS. Pharmacokinetic studies in the rabbit show that after intravenous administration (100 mg/kg) ARTS is metabolized rapidly to DQHS and has a t1/2 of 1.7 min in blood. DQHS data were fit to non-linear regression models consisting of the sum of two exponential terms. For phases 1 and 2, t1/2 values of 3.0 +/- 0.4 and 29 +/- 2 min were calculated, respectively. In vitro studies in which ARTS was incubated with blood from various species show that rabbit blood hydrolyzes ARTS at a much greater rate than rat or human blood. Incubation of ARTS with rabbit blood in the presence or absence of diisopropylfluorophosphate suggested that this hydrolysis reaction is catalyzed by plasma and red blood cell esterases. These results suggest that future pharmacokinetic studies in both animals and man should focus on the measurement of DQHS rather than ARTS.

Animals↗
PubMed1987

Effectiveness of silicone oil removal from rabbit eyes.

Silicone oil (1000 and 12,500 cs) and fluorosilicone oil (1000 and 10,000 cs) were dyed red and injected into a gas-created space in the vitreous cavity of 51 rabbit eyes. Later the oils were removed from the vitreous cavity either by lavage with balanced salt solution (group 1, 27 eyes) or by injecting a sodium hyaluronate solution, followed by lavage with balanced salt solution (group 2, 24 eyes). The average amount of oil retained in the vitreous cavity in group 1 was 0.0675 ml, and occasionally a large amount of oil was found (more than 0.1 ml in 30% of eyes). The average amount of oil retained in group 2 was 0.0114 ml, and no eye retained more than 0.1 ml of oil. The difference between the two groups was statistically significant (p less than 0.02), but there was no significant difference in oil retention within either group between the different kinds of oils, or between different viscosities of oil. The data suggest that residual oil can persist in the vitreous cavity despite thorough lavage, and that removal of silicone oil with the use of a sodium hyaluronate solution significantly lowers the risk of a large amount of residual silicone oil that is occasionally seen with conventional removal methods.

Animals↗
PubMed1987

Glutathione mixed disulfide inhibitors of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase.

Six glutathione-containing inhibitors of the human NADP-linked 15-hydroxyprostaglandin dehydrogenase have been isolated from placental homogenates. Glutathione disulfide is one of these inhibitors. Although the structures of the other five have not been fully elucidated, all are disulfides. Studies with these compounds and with other mixed disulfides have shown that the glutathione mixed disulfides of beta-mercaptopyruvate, mercaptoacetate, and beta-mercaptolactate are more effective inhibitors of the enzyme than are the glutathione-containing mixed disulfides isolated from placental homogenates. beta-Mercaptolactate is particularly noteworthy because of its low Ki (0.13 microM). The results reported here suggest that the activity of the prostaglandin dehydrogenase may be influenced in vivo by various glutathione mixed disulfides.

Disulfides↗
PubMed1987

Irreversible inhibition of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase/9-ketoprostaglandin reductase by glutathione thiosulfonate.

Oxidation of glutathione disulfide by a mixture of performic and hydrochloric acids leads to the formation of several compounds that are stronger inhibitors than glutathione disulfide of the placental enzyme that possess both NADP-linked 15-hydroxyprostaglandin dehydrogenase and 9-ketoprostaglandin reductase activities. The only one of these inhibitors that has been identified is glutathione thiosulfonate. The others are unstable and may include glutathione sulfinyl sulfone and glutathione disulfone. Since the enzyme appears to have a glutathione binding site in close proximity to its active site and glutathione thiosulfonate reacts with free sulfhydryl groups, the effects of this thiosulfonate on the enzyme were examined in more detail. Glutathione thiosulfonate and methyl methanethiosulfonate cause a time-dependent irreversible inhibition of both the hydroxyprostaglandin dehydrogenase and the ketoprostaglandin reductase activities, presumably by reacting with a free sulfhydryl at the prostaglandin binding site. Experiments with PGA1-glutathione show that this sulfhydryl is not necessary for the catalytic activity of the enzyme as long as the substrate can bind at the glutathione site.

Binding Sites↗
PubMed1987

Use of high-density fluorosilicone oil in open-sky vitrectomy.

During prolonged open-sky vitrectomy, fluid accumulates in the suprachoroidal and subretinal spaces and the resultant ballooning of the choroid and of the retina interferes with the surgery. Fluorosilicone oil (polymethyl-3,3,3-trifluoropropylsiloxane) with a specific gravity of 1.28 was tested for use as a temporary vitreous substitute during open-sky vitrectomy. After open-sky vitrectomy and bullous retinal detachment in pigmented rabbits, fluorosilicone oil flattened the retina completely in nine of nine eyes, whereas 1% sodium hyaluronate solution flattened the retina completely in only four of nine eyes. The flattening effect of fluorosilicone oil on the retina was also better than that of 1% sodium hyaluronate in an experiment with retinal detachment and giant retinal tear after open-sky vitrectomy.

Animals↗
PubMed1985

Metabolism of a potential 8-aminoquinoline antileishmanial drug in rat liver microsomes.

The metabolism of the 8-aminoquinoline, 8-(6-diethylaminohexylamino)-6-methoxy-lepidine dihydrochloride (WR 6026 X 2HCl), was studied in a rat hepatic microsomal system. The results show that WR 6026 X 2HCl was metabolized into two more polar compounds. The structures of these metabolites as proven by gas chromatography-mass spectrometry, ultraviolet absorption, and high performance liquid chromatography were: 8-(6-ethylaminohexylamino)-6-methoxy-lepidine (metabolite 1) and 8-(6-diethylaminohexylamino)-6-methoxy-4-hydroxymethyl quinoline (metabolite 2). The formation of both metabolites was NADPH dependent and also linearly dependent on incubation time and microsomal protein concentration at 0.24 mM WR 6026 X 2 HCl. Studies on the effects of pretreatment of animals with either phenobarbital or Aroclor 1254 suggest that cytochrome P-450 isozymes catalyzed both N-deethylation and hydroxylation reactions. N-deethylase activity was induced by either pretreatment: however, hydroxylase activity was unaffected by phenobarbital pretreatment and significantly elevated by Aroclor 1254 pretreatment. These results suggest that these two reactions are catalyzed by different cytochrome P-450 isozymes. The formation of these two metabolites in vivo may play an important role in the antileishmanial activity of WR 6026 X 2HCl.

Aminoquinolines↗
PubMed1985

Structure-activity relationships of putative primaquine metabolites causing methemoglobin formation in canine hemolysates.

A rapid and reproducible in vitro test system was developed to measure the methemoglobin (MHb)-forming properties of various 8-aminoquinoline derivatives. Initial rates and extents of reaction were measured spectrophotometrically with either canine hemolysates from which ferrihemoglobin reductase was removed, or with purified human oxyhemoglobin (Hb). The results demonstrate that primaquine derivatives that can be oxidized to quinones or iminoquinones (5-hydroxy,6-desmethyl primaquine; 5-hydroxyprimaquine; 5,6-dihydroxy-8-aminoquinoline; and 5-hydroxy, 6-methoxy-8-aminoquinoline) are potent MHb-forming compounds. Studies on the extent of reaction in hemolysates and purified oxyhemoglobin suggest that the extent of MHb formation may be limited by the rate at which the corresponding iminoquinones or quinones arylate nucleophiles. The effects of glutathione, mannitol, ascorbate, and superoxide dismutase on the rate and extent of hemoglobin oxidation by 5,6-dihydroxy-8-aminoquinoline suggest that these compounds oxidize Hb similar to the mechanism known for dimethylaminophenol (DMAP), in which Hb oxidizes the quinoline to semiquinone radical and quinone species which are the oxidizing and arylating agents.

Aminoquinolines↗
PubMed1985

Six-week trial with diazepam: some clinical observations.

Side effects, improvement, and predictors of response were examined in 295 patients treated for greater than or equal to 1 week with diazepam; 234 of these patients completed 6 weeks of treatment. The greatest improvement occurred during the first week of treatment. Sedation was the predominant side effect. Predictors of improvement included low educational level, lack of previous treatment, presence of precipitating stress, low occupational and/or family adjustment, low levels of trait anxiety, and high levels of state anxiety.

Adult↗
PubMed1984

High-performance liquid chromatographic method for the analysis of a candidate 8-aminoquinoline antileishmanial drug using oxidative electrochemical detection.

An analytical method was developed for the quantitation of a candidate antileishmanial drug, 6-methoxy-8-(6-diethylaminohexylamino)-4-methylquinoline, dihydrochloride, in canine plasma. The assay utilized internal standard technique with a structural similar 8-aminoquinoline, 6-methoxy-8-(7-diethylaminoheptylamino)-4-methylquinoline, dihydrochloride, as the internal standard. The method employs a liquid-solid extraction procedure with prepackaged silica gel columns upon which the drug and internal standard are adsorbed, then selectively washed and eluted. Reversed-phase chromatography was then employed to analyze the extracted sample by means of oxidative electrochemical detection at +0.75 V. Good accuracy and precision were obtained over the range of concentration tested (10-1500 ng/ml plasma). Analyses of plasma samples from human volunteers given the drug demonstrate the method is also suitable for analysis of human plasma samples. The entire procedure is relatively simple and requires only 1 ml of plasma.

Aminoquinolines↗
PubMed1984

Gentamicin penetration into diseased appendix tissue.

Gentamicin concentrations in appendix tissue, serum, and peritoneal fluid were obtained in suspected cases of gangrenous or perforated appendicitis. Despite widely ranging gentamicin concentrations, no infectious complications developed. Correlations were made between the pathologic state of the tissue and the tissue gentamicin concentrations. Correlations were also made with tissue gentamicin concentrations and the time after the antibiotic dose to the time of sampling.

Adult↗
PubMed1982

The covalent structure of apolipoprotein A-I from canine high density lipoproteins.

The complete amino acid sequence of apolipoprotein A-I (apo-A-I) from canine serum high density lipoproteins (HLD) has been determined by automated Edman degradation of the intact protein and proteolytic fragments derived therefrom. The major strategy involved analysis of overlapping sets of peptides generated by cleavage at lysyl residues with Myxobacter protease and by tryptic hydrolysis at arginines in the citraconylated protein derivative. Canine apo-A-I has 232 residues in its single polypeptide chain and its covalent structure is highly homologous to one of the two reported sequences for human apo-A-I. As in the case for the human apoprotein, predictive analysis of the canine apo-A-I sequence suggests that it comprises a series of amphiphilic alpha helices punctuated by a periodic array of prolyl residues. Human HDL contains a second major protein component, apolipoprotein A-II (apo-A-II) that is lacking in HDL from dog serum. The absence of apo-A-II in canine HDL raised the possibility that the apo-A-I from this source might contain within its primary structure sequences related to apo-A-II and thus perform the dual function of both proteins in one. Our analysis proves that canine apo-A-I has all of the structural features of human apo-A-I and that it is not an A-I: A-II hybrid molecule.

Amino Acid Sequence↗
PubMed1982

Disposition of the diastereoisomer of mefloquine in mice.

The disposition of the diastereoisomer of mefloquine, WR 177,602 . HCl, was examined over a 168-hour period after 10 mg/kg of the 14C-labeled drug was administered orally to female albino ICR mice. This drug was absorbed readily. 2 h after dosing, the drug was distributed throughout the animal body with a large percent of the administered dose found in the eyes, submaxillary salivary glands, lungs, spleen, liver, gallbladder plus bile, kidney and carcasses. The elimination half-life of the unmetabolized WR 177,602 in plasma was estimated to be 16.1 h. The major route of excretion of the drug was via the feces (70%), with 23% in the urine 168 h. The elimination half-lives of the unmetabolized drug in urine and feces were 8.0 and 6.9 h, respectively. The disposition of WR 177,602 . HCl was similar to its erythrodiastereoisomer in female mice.

Animals↗
PubMed1980

Sequence of the N-terminal half of Bacillus amyloliquefaciens alpha-amylase.

Bacillus amyloliquefaciens alpha-amylase (1,4-alpha-D-glucan glucanohydrolase. EC 3.2.1.1), which is commercially supplied as 'Bacillus subtilis alpha-amylase' does not cross-react immunologically with B. subtilis alpha-amylase. This enzyme (from B. amyloliquefaciens) was cleaved by treatment with CNBr into seven fragments. Peptide A was selected for sequence determination. It is the longest one, containing 185 amino acids (i.e. approx. 50% of the total molecule) and connects to the hexapeptide of the N-terminus. Its primary structure was aligned by use of various proteolytic enzymes. The sequence of amino acids 181-184 is identical with that of amino acids 14-17 of the alpha-amylase isolated from B. subtilis (except that amino acid 183 is asparagine rather than aspartic acid).

Amino Acid Sequence↗