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Biomedical subjects

H Chung

Publications and source records attributed to H Chung.

At least 109 records · Page 6Linked to original sources

Dermal absorption of niclosamide in rats and minipigs.

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.

Administration, Cutaneous↗

Pharmacokinetics of pyridostigmine in dogs.

The pharmacokinetics of the cholinesterase inhibitor pyridostigmine has been studied in six male Beagle dogs after iv infusion and after oral doses as an immediate-release syrup and as an extended-release tablet, all at a level of approximately 0.6 mg/kg. Pyridostigmine was characterized as a drug of relatively long terminal half-life (8.3 h +/- 2.1 SD), low systemic clearance (13 mL/min/kg +/- 1 SD) and high volumes of distribution (Vd lambda z, 8.7 L/kg +/- 1.9 SD and Vdss, 3.9 L/kg +/- 0.9 SD). The ratio of mean residence times in tissues and plasma was greater than 4, indicating a high affinity of peripheral tissues for the drug. This ratio was about twofold higher in three of the dogs than in the others. Pyridostigmine was slowly and incompletely bioavailable in these dogs; the systemic availability was 44.4% +/- 4.3 SD from the syrup and 33.6% +/- 9.5 SD from the tablet. Pyridostigmine disposition in these dogs was largely determined by distribution processes.

Administration, Oral↗

Cellular components of proliferative vitreoretinal membranes.

To understand the pathogenesis of proliferative vitreoretinal membrane formation which occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), etc., accurate identification of the cellular components of the membrane is needed. This study was performed to identify cellular components of the membranes by means of immunohistochemical technique. 11 proliferative vitreoretinal membranes which were surgically obtained from 7 eyes with PVR and 4 eyes with PDR were stained with monoclonal antibodies against cytokeratin, glial fibrillary acidic protein (GFAP), or vimentin using immunoperoxidase technique (ABC method). In the PVR membranes, mean cell positivities for cytokeratin, GFAP and vimentin were 48%, 1% and 92%, respectively and in the PDR membranes, 0%, 5% and 93%, respectively. The above results suggest that retinal pigment epithelial cells and fibroblasts are major cellular components of PVR membranes, and that mesenchymal cells are major cellular components and glial cells are minor cellular components of PDR membranes.

Adolescent↗

Subchronic oral toxicity of pyridostigmine bromide in rats.

This study evaluated the oral toxicity of pyridostigmine bromide in Sprague-Dawley rats when administered for 13 weeks by daily gavage. Groups of 10 rats/sex received doses of 0, 5, 15, 30, or 60 mg/kg/day. Toxicity was limited to exaggerated cholinergic stimulation at doses of 15 mg/kg/day or greater. Significant findings included tremors and inhibition of RBC acetylcholinesterase. Thus, 5 mg/kg/day of pyridostigmine bromide appears to be the no observed toxic effect level under the conditions of the present investigation.

Administration, Oral↗

Pharmacokinetics of the anti-leishmanian agent WR 6026 in dogs.

The pharmacokinetics of the anti-leishmanial agent WR 6026 (8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride) has been studied after single intravenous infusion and oral doses of 5 mg (base)/kg to 6 Beagle dogs. After single intravenous infusions of 15 min, plasma concentrations of unchanged drug declined bi-exponentially from a mean maximum of 1203 ng/ml +/- 277 SD at the end of infusion to the limit of quantitation during 16 hours. After single oral doses, the mean Cmax of 23 ng/ml +/- 14 SD occurred at a mean Tmax of 2.2 hours +/- 1.3 SD. During 72 hours after the intravenous and oral doses, 0.6% and less than 0.2% of the dose respectively was excreted unchanged in the urine. The mean terminal-life of WR 6026 after the infusion doses was +/- 0.3 SD, but after the oral doses, plasma concentrations of drug were too low to allow estimation of the terminal half-life. The systemic clearance of WR 6026 (43.5 ml/min/kg) greatly exceeded the nomina, plasma flow (ca. 22 ml/min/kg) and indicated considerable extra-hepatic and extra-renal elimination of WR 6026 in dogs. The mean systemic availability of WR 6026 after the oral doses was ca.4%. The mean volumes of distribution of WR 6026 in dogs were 3.3 litres/kg +/- 1.1 SD (V(ss)) and 7.7 litres/kg +/- 2.4 SD (V(area)). These data characterise WR 6026 as a drug of relatively high systemic clearance, large volume of distribution, relatively short half-life and low systemic availability, probably due to presystematic elimination in the liver.

Administration, Oral↗

Pharmacological and toxicological evaluation of orally administered pyridostigmine in dogs.

Pyridostigmine bromide, a reversible cholinesterase inhibitor, was administered orally (capsule gavage) to beagle dogs (10-15 months of age) of both sexes once daily at 5, 10, or 20 mg/kg for 14 days; every 8 hr at 2 or 5 mg/kg for 28 days; or every 8 hr at 0.05, 0.5, or 2 mg/kg for 3 months as part of its preclinical safety assessment. A small portion of the dogs receiving pyridostigmine for 3 months were allowed an untreated recovery period of an additional 3 months. Daily doses of 10 or 20 mg/kg were lethal to some of the dogs when given for up to 14 days and caused severe intestinal distress, including diarrhea, emesis, and reddened feces in all animals. The cause of death was intestinal intussusception. Signs of systemic toxicity apparent at these doses included hypersalivation and tremors. Similar but less severe effects were produced by 5 mg/kg per day; plasma cholinesterase activities were inhibited by all three doses in a dose-related manner. Signs of toxicity in the 28-day and 3-month studies were generally limited to the gastrointestinal tract and included diarrhea or soft stools and reddened or mucoid-containing stools; these signs appeared to reverse upon discontinuation of the drug. A single dog at 2 mg/kg every 8 hr developed an apparent intussusception. There were no pathological changes in clinical chemistry, hematology, or urinalysis parameters associated with doses of 0.05, 0.5, or 2 mg/kg every 8 hr for up to 3 months, nor were any drug-related lesions observed upon gross necropsy and microscopic evaluation of the major tissues and organs. Red blood cell (RBC) acetylcholinesterase (AChE) activities in the 3-month study were inhibited by approximately 10, 50, and 70% in the 0.05, 0.5, and 2 mg/kg every 8-hr dose groups, respectively, and these degrees of inhibition were maintained throughout the period of treatment. These data suggest that prolonged oral administration of pyridostigmine at doses sufficient to cause profound and sustained inhibition of RBC AChE activity (i.e., as high as 70%) cause mainly local, gastrointestinal distress related to altered intestinal motility. At the extreme, this can be manifested as a life-threatening intestinal intussusception. Systemic anticholinesterase effects (other than enzyme inhibition) were observed only at doses of 2 mg/kg and greater, while local (gastrointestinal) effects and inhibition of RBC AChE were observed at doses as low as 0.05 mg/kg.

Administration, Oral↗

[Clinical application of intermaxillary traction for temporomandibular disorders].

Occlusal splint has been usually used for TMJ arthrosis as a conservative treatment, but the range of its application is narrow and less effective. This study is to evaluate the effect of the pivoting splint with intermaxillary rubber traction, to report the results of the pivoting splint with intermaxillary rubber traction which was used 24 patients.

Animals↗

Detection of 3,4-dihydroxyphenylglycolaldehyde in human brain by high-performance liquid chromatography.

The monoamine oxidase A metabolite of noradrenaline, 3,4-dihydroxyphenylglycolaldehyde, is the precursor of 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylglycol, metabolites of noradrenaline. Owing to difficulties in purifying this aldehyde, it has not been previously characterized or identified in biological sources. This paper describes an enzymatic synthesis, purification, and characterization of 3,4-dihydroxyphenylglycolaldehyde. The aldehyde metabolite is identified in postmortem human brain using high-performance liquid chromatography and electrochemical detection. We estimate the concentration in human hippocampus to be 0.164 +/- 0.05 nmol/g. The importance of this aldehyde metabolite of noradrenaline is discussed.

Adsorption↗

Comparative evaluation of caffeine and theophylline for weaning premature infants from the ventilator.

Expedient weaning of infants from the respirator minimizes the risk of complications associated with assisted ventilation. Since theophylline and caffeine decrease apnea and enhance respiratory effort, we conducted a blinded, randomized comparative evaluation of each drug to determine extubation time and incidence of reintubation. Forty-five clinically stable premature infants receiving mechanical ventilation on minimal settings randomly were assigned to receive either theophylline (n = 23) or caffeine (n = 22) at least 1 day before and 5 days after extubation. From study entry to extubation, the mean number of days was 2.7 for both theophylline- and caffeine-treated infants. Three theophylline- and three caffeine-treated infants developed respiratory failure necessitating reintubation (NS). These findings indicate that for premature infants on minimal respiratory settings, the duration of intubation and the incidence of reintubation after treatment with theophylline or caffeine were similar.

Caffeine↗

The effect of cryotherapy on proliferative vitreoretinopathy (PVR).

Cryotherapy is implicated for inducing or aggravating proliferative vitreoretinopathy (PVR) by releasing retinal pigment epithelial (RPE) cells. These are based on the fact that PVR rarely occurs in a non-operated eye, and many of the PVR patients have received cryotherapy during surgery. Nonetheless, eyes with diathermy also developed PVR, and although there have been many experiments, the effect of cryotherapy on inducing PVR has not been proven experimentally in the living eye. We made retinal tears in living rabbit eyes, and applied cryotherapy on one eye of each rabbit. The result was compared histologically with the contralateral noncryothermized control eye. There was no statistically significant difference between the two groups concerning the migration of RPE, and the proliferation of RPE. Although the formation of an epiretinal membrane was more obvious in the cryothermized group, the difference was not statistically significant.

Animals↗

Clinical analysis of uveitis.

Uveitis can be classified in a variety of ways and this fact makes it difficult to compare results. Therefore we classified uveitis by the location with the method of Henderly; anterior-, posterior-, intermediate- and panuveitis. We determined the frequency of occurrence, etiology and clinical characteristics of various forms of uveitis. We conducted a retrospective analysis of 683 patients with uveitis seen at Seoul National University Hospital from January 1978, to December 1987. The results were as follows. 1. 192 cases (28.1%) occurred as anterior uveitis, 218 cases (31.9%) as posterior uveitis, 166 cases (24.3%) as panuveitis and 107 cases (15.7%) as pars planitis. Posterior uveitis was the most common form of uveitis. 2. In cases of anterior uveitis, 142 cases (74.0%) were idiopathic, traumatic uveitis was seen in 18 cases. In posterior-uveitis, 111 cases (50.9%) were idiopathic, retinal vasculitis including Eales' disease in 60 cases (27.5%), toxoplasmosis in 23 cases (10.6%). In cases of panuveitis, idiopathic form occurred in 80 cases (48.2%), Behçet's disease in 41 cases (24.7%). The idiopathic form was the most common entity in all locations of uveitis.

Adolescent↗

[Arthroscopic surgery for habitual dislocation of the temporomandibular joint].

This study is to evaluate the effect of the arthroscopic surgery for habitual dislocation of the temporomandibular joint. Conclusively, it is believed that arthroscopic surgery for habitual dislocation of the temporomandibular joint is easier method, has fewer complications, and lower recurrence rate, when compared with the conventional temporomandibular joint surgery.

Arthroscopy↗

Chorioretinal disease patterns in congenic mice following intraocular inoculation with HSV-1.

Disease patterns and immunologic parameters were studied employing inbred and Igh-1 disparate congenic mice to determine the role of host genetics and Igh-1-linked gene products in the von Szily model of viral chorioretinitis. Following intracameral inoculation of 1.5 x 10(4) PFU HSV-1 (KOS), 100% of BALB/c (Igh-1a), 62% of A/J (Igh-1e) and none of the C57BL/6J (Igh-1b) inbred mice developed contralateral necrotizing chorioretinitis. Multigenic differences between inbred mice prohibit conclusions about the specific role of Igh-1-linked immune regulation in this model. In order to more exactly define Igh-1-specific restriction of HSV-1-mediated chorioretinitis, Igh-1-disparate, congenic BALB/c mice were studied following both anterior chamber and intravitreal inoculation protocols. Anterior chamber inoculation resulted in contralateral retinal necrosis in 75% of BALB/c (Igh-1a) mice, 30% of C.AL-20 (Igh-1d) and 5% of the C.B-17 (Igh-1b) congenic mice; all strains showed ipsilateral retinal sparing. Following intravitreal inoculation of HSV-1 a similar restricted disease pattern was found in contralateral eyes. Contralateral chorioretinitis developed in 30% of BALB/c, 15% of C.AL-20 and 6% of C.B-17 mice. Ipsilateral disease, however, was found in all murine strains. These disease patterns developed despite equivalent suppression of systemic DTH and equivalent RPE permissivity to viral replication. These data demonstrate that host genetics strongly regulates contralateral HSV-1-mediated chorioretinal disease patterns by a mechanism unrelated to the development of systemic suppression of DTH and specifically support a dominant role for gene products linked to the Igh-1 locus in the immunomodulation of ocular disease.

Animals↗

Reevaluation of corneal complications after closed vitrectomy.

Corneal complications after closed vitrectomy were analyzed in patients treated by the same surgeon from January 1980 through December 1986. Of 428 eyes (400 patients), 64 (15%) had corneal complications, 58 (13.6%) had epithelial defects, and 12 (2.8%) had corneal edema. Among 206 diabetic eyes, 41 (19.9%) had corneal complications. Of 222 nondiabetic eyes, only 23 (10.4%) showed complications. Multiple regression analysis of possible contributing factors was performed. Diabetes, intraoperative lensectomy, and history of vitreous surgery were related significantly to the occurrence of all corneal complications combined. Our series showed a significantly decreased complication rate when compared with a previous study. Improved preoperative surgical preparation and intraoperative technique to minimize corneal trauma may have accounted for the decrease.

Cornea↗

Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone.

Risk of withdrawal was investigated in a prospective, double-blind comparison of clorazepate dipotassium, a benzodiazepine with a long half-life, and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious outpatients. Patients were treated with therapeutic doses of clorazepate dipotassium (15 to 60 mg/d) or buspirone hydrochloride (10 to 40 mg/d) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped. There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group. For the clorazepate group, there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects. For the buspirone group, a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population.

Adult↗

Methemoglobin formation resulting from administration of candidate 8-aminoquinoline antiparasitic drugs in the dog.

In vivo methemoglobin (MHb) formation caused by five 8-aminoquinoline compounds was tested in beagle dogs. Male beagle dogs were dosed orally once per day at 0.0116 mmol/kg for 4 consecutive days with primaquine (8-[4-amino-1-methylbutyl)amino]-6-methoxyquinoline, diphosphate), three candidate 8-aminoquinoline antimalarial drugs (WR 225,448 5-(3-trifluoromethyl)phenoxy-4-methyl primaquine, succinate); WR 238,605 2,6-dimethoxy-5-(3-trifluoromethyl)phenoxy-4-methyl primaquine, succinate; or WR 242,511 5-hexoxy-4-methyl primaquine, diphosphate dihydrate), or a candidate 8-aminoquinoline antileishmanial drug WR 6026 (8-[(6-diethylamino)amino]-6-methoxy-4-methyl quinoline, dihydrochloride). MHb and total hemoglobin levels were determined daily prior to dosing and for 29 days after drug administration. All compounds caused prolonged levels of MHb that peaked at Days 4 to 5 with disappearance half-lives of 5 to 9 days. Peak percentage MHb of primaquine, WR 6026, WR 238,605, WR 225,448, and WR 242,511 was 6.3, 20.7, 16.0, 25.3, and 48.1%, respectively. Total MHb as measured by area under the time-concentration curve was highest for WR 242,511, followed by WR 225,448, WR 238,605, WR 6026, and primaquine, respectively. The results of this study, in conjunction with other toxicity and efficacy studies, have been utilized to select one of these compounds for development as a replacement for the antimalarial drug primaquine, and also to characterize the MHb-forming properties of WR 6026.

Aminoquinolines↗

Extraction of retinol and cholesterol by intraocular silicone oils.

According to their solubility parameters, retinol and its derivatives, as well as cholesterol and other lipophilic substances, are predicted to dissolve in intraocular silicone and fluorosilicone oils. Calf retinas were extracted in vitro with these oils and the oils then analyzed spectrophotometrically. The following levels were found after extraction for 4 and 48 hours, respectively: for retinol, silicone oil, 0.5 and 3.7 micrograms/ml, and fluorosilicone oil, 0.5 and 3.3 micrograms/ml; for cholesterol, silicone oil, 0.5 and 6.4 micrograms/ml, and fluorosilicone oil, 0.8 and 3.7 micrograms/ml. In in vivo experiments, intraocular oils were removed from rabbit eyes at 4 days to 10 weeks after injection. The retinol levels were 1.7 to 11.4 micrograms/ml in silicone oil and 2.4 to 7.3 micrograms/ml in fluorosilicone oil; the cholesterol levels were 2.7 to 12.6 micrograms/ml in silicone oil and 7.5 to 15.6 micrograms/ml in fluorosilicone oil. Fluorosilicone and silicone oils (1000 cs) removed from human eyes at 7.3 and 102.0 weeks postoperatively had a retinol content of 5.4 and 2.9 micrograms/ml, respectively. Silicone oil of 1000 cs removed from a patient 51 weeks postoperatively and silicone oil of 12,500 cs removed 96 weeks postoperatively gave reaction characteristics for cholesterol, 230 and 99 micrograms/ml, respectively.

Animals↗