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Biomedical subjects

K Huh

Publications and source records attributed to K Huh.

At least 55 records · Page 3Linked to original sources

Disposition and metabolism of rifapentine, a rifamycin antibiotic, in mice, rats, and monkeys.

Rifapentine is a cyclopentyl derivative of rifampin under development for the treatment of Mycobacterium tuberculosis and Mycobacterium avium complex infections. These studies were designed to investigate the disposition and biotransformation of single iv and oral doses of 14C-rifapentine in mice, bile duct-cannulated and uncannulated rats, and monkeys. Mass balance studies included 14C analyses of urine, feces, bile, cage wash, carcasses, and cage air collected for up to 120 hr postdose. Separation of radioactive compounds extracted from urine, bile, and feces was conducted using high-performance liquid chromatography and radioisotope detection. The mass spectra of selected chromatographic peaks were obtained. Disposition results were similar for all three species. Less than 5% of the radioactive dose of 14C-rifapentine was recovered in urine, indicating that renal excretion is a minor route of elimination in these species. The major route of elimination of radioactivity was into the feces, where more than 75% of the radioactivity was recovered. Biliary excretion was the major route of elimination of radioactivity in bile duct-cannulated rats dosed either po or IV. Radiochromatograms were similar for fecal samples from animals dosed by IV or orally. Ten regions of radioactivity were observed in mouse and rat fecal sample radiochromatograms, and seven regions of radioactivity were observed in monkey fecal sample radiochromatograms. The most abundant compound identified in feces was usually intact rifapentine (27%-41% of dose in mouse, 3%-35% of dose in rat, and 17%-29% of dose in monkey). Other peaks identified or characterized in feces based on liquid chromatography/ultraviolet/14C and/or liquid chromatography/mass spectrometry methods included 25-desacetyl-rifapentine, 3-formyl-25-desacetyl-rifapentine, and 3-formyl-rifapentine. The compounds rifapentine, 25-desacetyl-rifapentine, and 3-formyl-rifapentine were present in rat bile samples. These studies show that the metabolism and disposition of rifapentine in mice, rats, and monkeys were similar.

Animals↗

Estrogen blocks neurotoxic effects of beta-amyloid (1-42) and induces neurite extension on B103 cells.

Clinical studies have shown that estrogen replacement therapy is associated with reduced risk of Alzheimer's disease (AD). We tested whether or not estrogen blocks neurotoxic effects of beta-amyloid (1-42) (A beta1-42) on cultured B103 cells. A beta1-42 (1 microM) induced typical necrotic cell death, as revealed by light and electron microscopic examinations. Co-administration of estrogen not only blocked A beta1-42 toxicity to a large degree, but also enhanced neurite extension. Pretreatment with estrogen was even more effective in blocking A beta1-42 toxicity. When added 18 h after the beginning of A beta1-42 treatment, estrogen was still effective in halting the progress of cell death and enhancing neurite extension. The protection against A beta1-42-induced neuronal death by estrogen was unlikely due to a blockade of lipid peroxidation injury, since estrogen completely failed to attenuate ferrous chloride-induced cell death. These results demonstrate that estrogen blocks A beta1-42-induced neurotoxicity and enhances neurite extension on B103 cells, both of which may well be underlying mechanisms of beneficial effects of estrogen in AD.

Amyloid beta-Peptides↗

HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: possibility of coinfection in these patients must be considered in HBV-high endemic area.

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C-infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV-RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non-A and non-B chronic hepatitis patients without HCC who had the same profiles of anti-HCV, HCV-RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A and non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti-HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non-A non-B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non-A and non-B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viraemia should be considered and molecular analysis for HBV-DNA performed.

Adult↗

Mitochondrial gene transfer ribonucleic acid (tRNA)Leu(UUR) 3243 and tRNA(Lys) 8344 mutations and diabetes mellitus in Korea.

The high prevalence of diabetic patients with a mutation in the mitochondrial gene (the 3243 and 8344 bp mutations) has been identified in Japan. To determine the prevalence of diabetic patients with those mutations in Korea, we randomly screened selected 503 clinical diabetic patients regardless of their diabetes types. We found only 1 patient with the mitochondrial DNA mutation at position 3243 (percent mutation, 32%), and the mitochondrial DNA mutation at position 8344 was not found in any of the patients. The affected subject was a 22-yr-old man with a history of myoclonic epilepsy and mild sensorineural hearing loss, a 1-yr duration of diabetes mellitus, and a low level C peptide response to oral glucose. Because of the low frequency of these mutations in the Korean diabetic population, we concluded that these particular mutations of mitochondrial DNA may not be a common contributor to diabetes mellitus in Korea.

Adult↗

Experiences of epilepsy surgery in intractable seizures with past history of CNS infection.

We studied the clinical characteristics, location of epileptogenic regions, and the surgical outcomes in 18 patients with intractable epilepsy associated with previous CNS infections. All patients underwent an extensive presurgical evaluation and 11 patients had intracranial EEG monitoring. On the basis of presurgical evaluation, epileptic regions were localized to the mesial temporal (n = 12) and the neocortical (n = 6) regions. The age of the time of CNS infection was significantly younger and the latent period of non-febrile seizures after CNS infection was longer in patients with mesial temporal lobe epilepsy (MTLE). MRI showed hippocampal atrophy and hippocampal signal changes in 11 of 12 patients with MTLE. Among 6 patients with neocortical epilepsy (NE) 5 patients had normal MRI and one showed cerebral hemi-atrophy. Surgery was successful (class I & II) in all patients with MTLE, however, in the patients with neocortical epilepsy, seizure-free results were not achieved in any patients after resective surgery (6 patients) and only 2 patients achieved Class II outcomes after a second epilepsy surgery consisting of neocortical resection. Patients with MTLE after CNS infection were differentiated from the group of neocortical epilepsy by an earlier onset of CNS infection, a prolonged latent period and a higher frequency of meningitis. The characteristic pathology in this group was hippocampal sclerosis and the surgical result was excellent. Neocortical epilepsy following CNS infection usually had no focal lesion on MRI and was associated with a relatively poor surgical result. This study suggested that the surgical outcome was influenced by the type of epileptic syndromes rather than the etiology of seizures. The association of MTLE with the younger age of CNS infections and with meningitis more frequently suggested that the neocortical neurons during infancy or early childhood may be more resistant to the epileptogenesis, or that the CNS infections in patients with MTLE might be milder in severity to cause selective injuries to the hippocampal neurons during their vulnerable stage.

Adolescent↗

Role of nitric oxide in penile erection.

The present study was undertaken to investigate the role of nitric oxide (NO) in erectile physiology by correlating its action with the existence and activity of nitric oxide synthase (NOS), which produces NO. We applied Western blot analysis in both human and rat penile tissue. In the rat, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and spectrophotometric assay were also performed, in addition to in vivo electroerection study with pharmacological manipulation. Western blot analysis identified a protein of 155 KDa identical to the neural form of NOS in the human and rat penis. The NOS blot densities in the two species were similar, and both were lower than that in the rat cerebellum. Histochemical staining localized NOS to neurons innervating the corpora cavernosa, including the pelvic plexus, the cavernosal nerves and their terminal fibers within the corporeal erectile tissue, and dorsal penile nerves. NOS activity was also found in the cerebellum, urethra, penis, and urinary bladder, in decreasing order of intensity. Intracavernous injections of NOS inhibitor (L-NOARG or L-NAME in concentrations from 10(-6) M to 10(-3) M suppressed electrostimulation-induced erection in a concentration-dependent manner. Subsequent intracavernous injection of L-Arginine (10(-2) M) partially restored the erection. The neural form of constitutive NOS in the corpora cavernosa synthesizes NO, which mediates penile erection. Determination of cavernosal NOS expression or activity may permit characterization of certain pathological conditions that cause impotence.

Animals↗

The effect of rebamipide on gastric xanthine oxidase activity and type conversion in ethanol-treated rats.

Rebamipide, a novel antipeptic ulcer drug, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4-yl]-propionic acid, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intraperitoneal administration of rebamipide at 60 mg/kg body weight reduced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of rebamipide on alcohol-induced xanthine oxidase-type conversion and enzyme activity. It was also observed that the activity of xanthine oxidase was significantly inhibited by administration of rebamipide at 60 mg/kg body weight, leading to a significant reduction of lipid peroxide content in alcohol-treated rats. The results suggest that alcohol-induced gastric mucosal lesions might be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and the protective effect of rebamipide on gastric mucosal lesions would result from its ability to protect against oxidative stress on gastric mucosal lesions of alcohol-treated rats.

Alanine↗

Deletion of Rb1 gene in late osteosarcoma from survivor of unilateral retinoblastoma--a case report.

It has been well known that the survivors of retinoblastoma are prone to have osteosarcoma. But the secondary tumor usually occurs in bilateral, hereditary type of retinoblastoma. We report one case of osteosarcoma in a survivor of unilateral, sporadic retinoblastoma. A fourteen year old male presented with a painfully swollen distal forearm of 2 month duration. He had enucleated his left eye 10 years ago due to retinoblastoma with no other adjuvant therapy. We managed him with our conventional protocol and identified deletion of Rb gene from his pathological specimen by using the PCR-RFLP method. This result is unusual for unilateral nonhereditable retinoblastoma and may suggest gene level change even in sporadic cases. And Rb gene study may be helpful for unilateral, sporadic retinoblastoma patient in detecting the possibility of late osteosarcoma.

Adolescent↗

Relationship between the auditory P300 and the procedural memory function in drug-naive patients with Parkinson's disease.

We evaluated and compared procedural memory and auditory P300 event-related potential in age-matched normal controls (n = 15) and drug-naive patients with Parkinson's disease (n = 16). We used Gollin's incomplete picture test for visual procedural memory function and Tower of Hanoi puzzle for visuomotor procedural memory function. The mean latency of P300 was significantly prolonged in the Parkinsonian group than in the controls. In the neuropsychology test, the patients group revealed selective impairment of visuomotor procedural memory against preserved visual procedural memory. In the patients group, the latency of P300 was inversely correlated with performance of visuomotor procedural memory. These results suggest that prolonged auditory P300 event-related potential show the dysfunction of visuomotor procedural memory in the basal ganglia, which appears to be more selectively impaired than visual procedural memory in drug-naive patients with Parkinson's disease.

Event-Related Potentials, P300↗

Structures and biological activities of tobramycin-ticarcillin adducts.

Aminoglycosides and penicillins chemically interact when they are combined in vitro or in vivo. The resulting adducts are considered to be biologically inactive. The major adducts formed in he interaction between tobramycin and ticarcillin have been recently isolated in pure form in our laboratory. On the basis of mass, infrared, and proton magnetic resonance spectra, the major adducts appeared 10 be amides formed by an attack of the beta-lactam carbonyl group of ticarcillin by an amino group of tobramycin. All other moieties of ticarcillin were intact except that the beta-lactam ring was opened and was rotated by 120-130 degrees . The minimum inhibitory concentrations (MICs) of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 microg/mL for Staphylococcus aureus and Escherichia coli, and 160.0, 0.5, and 8.0 microg/mL for Pseudomonas aeruginosa. Thus, the major adducts possessed some antimicrobial activity, but not enough to be active in the treatment of infections. As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some cross-reactivity in the assay of tobramycin. However, it was insufficient to cause significant error in the measurement of tobramycin in human serum.

Anti-Bacterial Agents↗

Effect of sex hormones on lipid peroxidation in rat liver.

The role of sex hormones in hepatic lipid peroxidation, and in hepatic aldehyde oxidase and xanthine oxidase activities were investigated using rat liver homogenates. It was observed that male rat had a significantly greater content of malondialdehyde in liver than female. Among the sex hormones tested, estradiol, one of female hormones, markedly inhibited the formation of lipid peroxides in liver tissues in vitro. Especially, the inhibitory effect of estradiol appeared more remarkably in Fe+2-induced lipid peroxidation. The hepatic xanthine oxidase activity was decreased about 15% by 10(-6) M estradiol, whereas, the aldehyde oxidase activity was almost completely disappeared at the same concentration of estradiol. It implies that sex differences in lipid peroxidation is attributed to the suppression of free radical generating system by estradiol.

Aldehyde Oxidase↗

Establishment of pigmented choroidal melanomas in a rabbit model.

PURPOSE: To establish an animal model of pigmented choroidal melanoma. METHODS: Four melanoma cell lines originally isolated from melanotic tumors (B16F10, RPMI 1846, OCM 1, and IIB) were used to establish choroidal melanomas in 105 rabbits; 88 animals were immunosuppressed with cyclosporine. Tumor cells were implanted transclerally and examined with indirect ophthalmoscopy, ultrasound, and photography. RESULTS: Characteristic growth patterns were noted for each cell line. Animal cell lines typically produced choroidal tumors 3 to 4 mm in height within 2 weeks; human cell lines took an additional 7 to 10 days to achieve tumors of similar height. Tumors of heaviest pigmentation were generated consistently with the B16F10 cells, and with the other three cell lines only mild pigmentation was observed. Tumor shape varied depending on the source of implantation: diffuse, flat tumors were observed when cell suspensions were implanted, and nodular tumors were obtained with tumor fragments. Histopathologically, lesions were highly cellular, with rich vascularity and large numbers of mitotic figures. CONCLUSION: As the majority of human uveal melanomas are pigmented, the added feature of pigmentation associated with this model makes it more suitable for evaluating the role of newly developed phototherapies in the management of uveal melanoma.

Animals↗

Effects of neural transplantation on seizures in the immature genetically epilepsy-prone rat.

To study the hypothesis that neural transplantations can alter seizure susceptibility in a genetic animal model of epilepsy, 93 pubescent genetically epilepsy-prone rats with stage 9 seizures received either bilateral inferior colliculi (N = 21) or lateral ventricle (N = 42) transplants or sham transplants (N = 30). The grafts consisted of embryonic locus ceruleus, neocortical, or cerebellar tissue. Starting 2 days after the transplantation the rats were subjected to audiogenic stimulations every other day for 61 days. Latency to the running and tonic phase, seizure severity score, and duration of the tonic and clonic phase were compared in the neural transplant and sham-operated controls. Rats that received transplants had a longer latency to the tonic phase and a shorter duration of the clonic phase than the controls. At age 110 days the rats had electrodes implanted bilaterally into the angular bundle and were kindled. No difference in kindling rate was found between the rats that received neural grafts and the sham-operated controls. Cerebrospinal fluid concentration of norepinephrine was not altered by the transplants. This study demonstrates that the anticonvulsant effects of neural transplants, using the genetically epilepsy-prone model of epilepsy, are mild.

Acoustic Stimulation↗

Can we predict carbamazepine responsiveness in partial epilepsy?

We studied 153 patients with partial epilepsy who were placed on a carbamazepine monotherapy plan in order to evaluate the clinical factors that may determine drug responsiveness to carbamazepine. The subjects were divided into 3 groups based on their therapeutic outcome--complete seizure control (44%), significant seizure reduction (32%) and unsatisfactory control (24%). Fifteen tentative clinical factors were examined in relation to the therapeutic outcomes. Factors such as seizure type, number of generalized tonic-clonic seizures, age of onset, duration of illness, seizure frequency, previous treatment and EEG finding were relevant to drug responsiveness. However, other variables including mental retardation, etiology, febrile convulsion, positive family history and abnormal neurologic examination showed no significant correlation. Our data suggest that a potential success of carbamazepine treatment should not be underestimated even in patients with complicated clinical features.

Adolescent↗

Effect of neural transplants on seizure frequency and kindling in immature rats following kainic acid.

To study the hypothesis that neural transplantations can alter seizure susceptibility in a chronic animal model of epilepsy 260 immature rats (30- to 32-days-old) were administered a convulsant dosage of kainic acid (KA). Ten days later rats that had severe seizures following KA received either bilateral intracerebroventricular transplants of hippocampal (n = 27), neocortical (n = 29), cerebellar (n = 30), or locus ceruleus (n = 32) tissue, or underwent sham transplantation (n = 66). Spontaneous seizure frequency was assessed for 230 days following which the rats underwent entorhinal kindling. The percentage of rats developing spontaneous recurrent seizures was similar in the 4 transplant groups and the sham-operated controls. Rats receiving hippocampal and locus ceruleus transplants had fewer spontaneous seizures than the sham-operated controls or other transplant groups. However, there were no differences in afterdischarge thresholds or kindling rates in the 5 groups. This study demonstrates that the anticonvulsant effects of neural transplants, using this animal model are mild. Tissue type of the graft appears to be an important variable in the alteration of seizure frequency.

Animals↗

RETT's syndrome in Korea--report of two cases.

Rett's syndrome(RS) is a progressive neurodegenerative disorder characterized by exclusive occurrence in females, autistic behavior, dementia, gait ataxia, loss of purposeful use of the hands with stereotypic hand movement, and seizures. Initially RS was considered to be very rare; however, recent reports suggest that the prevalence is considerably higher and occurrence is world-wide. Because the pathophysiological process remains unknown, the diagnosis of RS is based mainly on its characteristic clinical features and course. We experienced two cases of RS which, to our knowledge, are the first reported in Korea. It is quite possible that many patients with RS not yet being diagnosed in Korea.

Child↗

Comparative cognitive effects of anticonvulsants.

We investigated the neuropsychological effects of carbamazepine, phenobarbital, and phenytoin in 15 partial complex epilepsy patients treated with each drug for 3 months, using a randomized double-blind, triple crossover design. Neuropsychological evaluation at the end of each treatment period included Digit Span, Selective Reminding Test, Digit Symbol, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 evoked potential, and Profile of Mood States. Employing anticonvulsant blood levels and seizure frequencies as covariates, the only significant difference was for Digit Symbol. Performance with phenobarbital was significantly worse than with the other 2 anticonvulsants despite phenobarbital's having had the lowest overall blood levels. Our data show that patients receiving carbamazepine, phenobarbital, and phenytoin have comparable neuropsychological performance on most measures. The results suggest that the differential cognitive effects of anticonvulsants may be subtle.

Adult↗

Human hippocampal EEG: effects of behavioral activation.

We studied spectral components of human hippocampal EEG in relation to behavioral status in 19 patients with intractable complex partial seizures who had depth electrodes implanted into the anterior hippocampi as a part of their preoperative evaluations. Behavioral conditions included: eyes closed resting, eyes open resting, eyes open with a verbal task, and eyes open with a visuospatial task. Hippocampal EEG spectral power uniformly decreased during behavioral activation. EEG activation was quantitatively different among the 3 activated conditions, with the most prominent change occurring during the visuospatial task. The degree of EEG activation corresponded inversely with the site of epileptic focus during the verbal task. The results demonstrate the response of human hippocampal EEG to behavioral activation. The magnitude of EEG change may reflect the degree of functional activation of the given hippocampus.

Adult↗