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Biomedical subjects

Y Park

Publications and source records attributed to Y Park.

At least 217 records · Page 12Linked to original sources
PubMed1993

A randomized, controlled trial of recombinant alpha-interferon therapy for chronic hepatitis B.

OBJECTIVES: To evaluate the effect of recombinant alpha-interferon in chronic hepatitis B. METHODS: Patients were stratified at entry according to their serum aspartate aminotransferase (AST) values, randomized to receive alpha-interferon (alfa-2b, 10 million units three times weekly) or to be untreated controls for 16 wk. Effect of therapy on levels of hepatitis B viral (HBV) DNA and aminotransferase activities in serum and hepatitis B e antigen (HBeAg) status was monitored. RESULTS: Forty-seven patients entered the trial; 11 of 25 (44%) patients receiving interferon responded by clearing HBeAg and HBV DNA within 6 months, compared to one of 22 (5%) controls (p < 0.05). Among those with serum AST values < 100 U/L, 33% responded and among those with AST values > 100 U/L, 60% responded. Within the 6-month study period, 36% of treated patients had normal serum alanine aminotransferase (ALT) values, and 16% had cleared hepatitis B surface antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg. Interferon was stopped early in three patients (6.5%), and dosage was reduced in a further 16 patients (35%) because of adverse effects. Predictive factors for a response were the pretreatment serum ALT and AST activities. CONCLUSIONS: alpha-Interferon therapy (three times weekly) is relatively well tolerated and is effective in clearing HBeAg and HBV DNA in approximately one-third of treated patients.

Adult↗
PubMed1992

Cloning of a Porphyromonas (Bacteroides) gingivalis protease gene and characterization of its product.

A clone expressing a Porphyromonas gingivalis protease from the recombinant plasmid (pYS307) has been identified in a genomic library of P. gingivalis W83. The cloned gene was localized to a 2.4-kb DNA fragment between BamHI and HindIII sites. When a 3.2-kb HindIII fragment of pYS307 was used as a probe in Southern hybridization, HindIII-digested chromosomal DNA of P. gingivalis W83, as well as those of W50 and W12, showed a single 3.2-kb hybridizing band, while that of P. gingivalis 33277 showed a 5.0-kb band. Colonies of E. coli containing pYS307 showed pronounced proteolytic zones on skim milk agar plates only when incubated in an oxygen-free environment. BSA substrate zymography of whole cell extract of E. coli containing pYS307 revealed a protease of approx. 80 kDa which was active under reducing conditions. These results suggest that the cloned protease is thiol-dependent. Antiserum to P. gingivalis W50 reacted with a single band of 80 kDa when a cell lysate sample of an E. coli JM83 containing pYS307 was prepared for electrophoresis in the absence of beta-mercaptoethanol. When samples were solubilized in the presence of beta-mercaptoethanol prior to electrophoresis, the antiserum reacted with the bands of 50 and 38 kDa, but there was no reaction observed at 80 kDa. The activity of the cloned protease was inhibited by TLCK, TPCK, EDTA, PMSF, iodoacetic acid and ZnCl2.

Cloning, Molecular↗
PubMed1992

A pilot study of ribavirin therapy for chronic hepatitis C.

Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used.

Adult↗
PubMed1992

A pilot study of 2',3'-dideoxyinosine for the treatment of chronic hepatitis B.

The nucleoside analog 2',3'-dideoxyinosine, currently being used to treat patients infected with the human immunodeficiency virus, has been shown to inhibit viral replication in certain cell culture systems of hepatitis B virus and the duck model of chronic hepatitis B infection. We studied the effect of dideoxyinosine on viral replication in patients with chronic hepatitis B. In the initial dose-finding phase, patients received sequential 2-wk courses of dideoxyinosine in escalating doses of 3, 6 and 9 mg/kg/day. In the second, long-term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of dideoxyinosine on hepatitis B were assessed by serial measurements of ALT, hepatitis B virus DNA and DNA polymerase activity in serum. Six patients completed the dose-finding phase, and five patients continued into the long-term treatment phase. No significant differences were seen in serum aminotransferases, hepatitis B virus DNA levels or DNA polymerase activity at any time during treatment when compared with pretreatment levels. All patients remained positive for HBeAg during treatment and during 6 mo of follow-up. Thus at the doses tested, dideoxyinosine had no appreciable effect on viral replication in patients with chronic hepatitis B.

Adult↗
PubMed1992

Drug-food interaction potential of clarithromycin, a new macrolide antimicrobial.

To evaluate the effect of food on bioavailability, clarithromycin and 14-hydroxyclarithromycin (active metabolite) pharmacokinetics were assessed in 26 healthy adult volunteers after ingestion of a single oral 500-mg dose of clarithromycin in a fasting state (2 hours before breakfast after an overnight fast) and a nonfasting state (0.5 hours after the start of breakfast). Clarithromycin and 14-hydroxy metabolite plasma concentrations were measured using a high-performance liquid chromatographic technique. Food intake immediately before dosing increased the extent of absorption from the 500-mg tablet formulation by approximately 25%. The mean increase in metabolite area under the plasma concentration-time curve was approximately 9%. These results suggest that clarithromycin can be taken without regard to timing in relation to meals.

Absorption↗
PubMed1992

A controlled trial of naloxone infusions for the pruritus of chronic cholestasis.

To test the hypothesis that opioid agonist activity contributes to the pruritus of cholestasis, a placebo-controlled single-blinded trial of naloxone, an opioid antagonist, was conducted in eight patients with primary biliary cirrhosis. After discontinuation of all conventional antipruritic medications, one or two continuous (24-hour) IV infusions of naloxone (0.2 micrograms.kg-1.min-1) and placebo solution were administered consecutively in an order that was not predetermined. Pruritus was assessed subjectively by means of four hourly recordings of a visual analogue score. In addition, objective measurements of scratching activity that were independent of gross body movements were continuously recorded using an apparatus specifically designed to measure the frequencies associated with this activity. No side effects associated with naloxone infusions were observed. Only scratching activity data obtained for the same periods of day and night during both naloxone and placebo infusions were compared. Naloxone infusions were consistently associated with a decrease in values of the scratching activity index. In addition, in 50% of the patients the infusions were associated with a decrease in visual analogue score. The mean decrease in scratching activity ranged from 29% to 96% (mean, 50%; P less than 0.001). These findings imply that increased opioid agonist activity contributes to scratching activity in cholestatic patients.

Adult↗
PubMed1992

Postanoxic oxidative injury in rat hepatocytes: lactate-dependent protection against tert-butylhydroperoxide.

Previous studies in this laboratory showed that hypoxia and anoxia enhance the susceptibility of hepatocytes to tert-butylhydroperoxide (TBH)-induced oxidative injury. To determine whether preceding exposure to anoxia affects postanoxic sensitivity to oxidative injury, viability was studied in hepatocytes incubated under anoxic conditions followed by reoxygenation without or with tert-butylhydroperoxide addition. Results showed that a preceding exposure to 60 min of anoxia substantially increased the vulnerability of cells to injury by the oxidant. Because substantial tissue lactate can accumulate during anoxia, the effect of increased lactate on postanoxic injury due to TBH was determined. Results showed that added lactate protected in a concentration-dependent manner. The TBH elimination rate was stimulated by lactate, and the pyruvate production rate approached the rate of TBH elimination. Thus, lactate protects against postanoxic oxidative injury by supplying reducing equivalents for peroxide reduction. This suggests that lactate accumulation during ischemia may be beneficial and that supplementation with lactate could be considered as a means to protect against postischemic injury.

Animals↗
PubMed1992

Protective effect of the dimer of 16,16-diMePGB1 against KCN-induced mitochondrial failure in hepatocytes.

The dimer and trimer of 16,16-dimethyl-15-dehydroprostaglandin B1 (16,16-diMePGB1) previously have been shown to have protective effects on mitochondrial function. To examine the potential mechanisms involved in protection against mitochondrial failure, we have studied the effects of the dimer of 16,16-diMe-PGB1 (dicalciphor) on mitochondrial function in hepatocytes exposed to KCN. Addition of micromolar concentrations of dicalciphor provided substantial protection against KCN-induced toxicity in a concentration- and time-dependent manner. Dicalciphor, however, had no effect on total or mitochondrial ATP losses in KCN-treated cells. The dimer prevented the marked loss of mitochondrial membrane potential (delta psi) and delta pH that occurs as a result of KCN treatment and prevented KCN-induced loading of phosphate in mitochondria. Furthermore, the dimer of 16,16-diMePGB1 also prevented KCN-induced mitochondrial and cellular swelling. These results demonstrate that dicalciphor protects against KCN-induced damage and that this protection is associated with regulation of specific mitochondrial ion transport functions.

Adenosine Triphosphate↗
PubMed1992

Influence of the stopcock on the efficiency of percutaneous drainage catheters: laboratory evaluation.

The effects of stopcocks on percutaneous fluid drainage were tested in a laboratory model by using a standard stopcock (6-French inner diameter) and a prototype stopcock (9-French inner diameter) connected to 8-, 10-, 12-, 14-, and 16-French catheters. Catheters were immersed in water alone or in viscous fluid with particulate matter, and the system was connected to low wall suction or gravity drainage. The average volume of fluid aspirated in a given period with and without a stopcock was compared for each catheter. The standard stopcock decreased drainage efficiency for these catheters by 13-42%. This decreased drainage efficiency was worse with the larger catheters. Particulate fluid blocked the stopcock connection for all catheters. With the prototype stopcock, drainage of water alone was reduced by 0-9% for the catheters of different sizes. Particulate fluid did not obstruct the prototype stopcock with any size catheter. With gravity drainage, the volume of water aspirated was reduced by 12-42% with the standard stopcock and by 3-6% with the prototype stopcock. These data suggest that stopcock connections greatly influence the efficiency of the percutaneous drainage systems. Stopcocks with larger inner diameters may improve drainage over that achievable with the stopcocks that are currently available.

Catheterization↗
PubMed1992

Protective effect of dicalciphor during mitochondrial failure.

Mammalian cells differ considerably in the duration of anoxia which they can tolerate despite the fact that dramatic bioenergetic changes occur rapidly. Previous studies indicate that the ability to tolerate anoxia is at least partly due to an endogenous signal transduction system that senses O2 deficiency and signal altered ion transport functions in the mitochondria. The responses included inhibition of ATP synthase, ADP/ATP exchange, inorganic phosphate uptake, mitochondrial swelling, and loss of the mitochondrial proton-motive force. An important distinction between KCN toxicity and anoxia is that KCN does not elicit these protective mechanisms. Thus, the ability of a compound to elicit these mechanisms in KCN-treated cells provides an assay for potential agonists of the endogenous protective mechanisms.

Animals↗
PubMed1991

Oxidative stress during hypoxia in isolated-perfused rat heart.

These data suggest that oxidative stress occurs at the low oxygen tensions which exist during perfusion of rat heart tissue with hypoxic medium. Importantly, no evidence was found for additional oxidative injury after 4 min reoxygenation when enzyme release is maximal in this system suggesting the oxygen paradox is unrelated to oxidative stress. However, the oxidative changes evident after 10-15 min of hypoxia do support the occurrence of free radical mediated injury at low oxygen tensions, and it is possible this injury is involved in the changes which lead to cell lysis at reoxygenation. The source of this oxidative stress is not known, but appears to be greater in mitochondria and may arise from an increased production of reactive oxygen species by this organelle. Whether the observed oxidative changes are directly injurious to a cell is not yet clear.

Animals↗
PubMed1991

Purity of ruthenium red used in pharmacological research.

The inorganic dye, ruthenium red, is an ammoniated form of ruthenium oxychloride. The purity of commercial samples of ruthenium red has been confused as commercial vendors often provide a "dye content" figure for their product, which some investigators have equated with purity. However, dye content is the same as ruthenium content and is not related to purity, although it will affect the relative molecular weight of this compound. As a result, concentrations of ruthenium red used in various biochemical studies have been calculated based on the supposed impurity of the commercial product, a product purified in the laboratory of the investigator, or by simply ignoring this purity question. Purity of four different commercial products as well as two different "purified" materials was determined by comparison of absorbance spectra and extinction coefficients. Taking into account differences in the relative ruthenium content of each preparation of ruthenium red, the results demonstrate no significant differences between these materials indicating that commercially available samples of ruthenium red are essentially pure.

Ruthenium Red↗
PubMed1991

Oxidative changes in hypoxic rat heart tissue.

Reactive O2 species appear to be generated both during hypoxia and at reoxygenation, but it has not been established whether these species interact with heart tissue and cause injury. Oxidative changes were evaluated in isolated rat heart perfused with Krebs-Henseleit medium containing 10 mM glucose and 2.5 mM calcium. After 5-10 min hypoxia, tissue glutathione (GSH) decreased while glutathione disulfide (GSSG), protein carbonyls, and thiobarbituric acid reactive substances (TBARS) increased compared with controls. Similarly, sarcolemmal and sarcoplasmic reticular Ca-ATPase activity (an enzyme susceptible to oxidative inactivation) decreased in response to 10 min hypoxia. These changes were more pronounced after 60 min of hypoxia when protein-GSH mixed disulfides were also increased. There were no further oxidative changes after 4 min reoxygenation when the release of lactate dehydrogenase (LDH) was maximal. Myocardial protein thiol and alpha-tocopherol contents were not significantly changed by either hypoxia or reoxygenation. Mitochondria also exhibited oxidative changes but with more pronounced increases in GSSG and mixed disulfides. There was no change in GSH or GSSG efflux into the coronary effluent during hypoxia, although, in parallel with LDH release, both increased after reoxygenation. Diamide (200 microM), t-butylhydroperoxide (20 microM), or purine (2.3 mM) + xanthine oxidase (0.01 U/ml) were infused for 10 min. Except for large diamide-induced changes in protein thiols and mixed disulfides, the magnitude of the changes produced by these oxidants was similar to those produced by hypoxia. These data show that changes consistent with oxidative processes occur in whole heart and mitochondria in response to hypoxia. The absence of marked signs of oxidation at reoxygenation suggest that enzyme release at this time is unrelated to oxidative stress.

Animals↗
PubMed1991

Oxidative changes in hypoxic-reoxygenated rabbit heart: a consequence of hypoxia rather than reoxygenation.

Tissue changes consistent with oxidative damage in hypoxic/reoxygenated heart tissue have not been well documented. We recently reported that oxidative perturbations were evident in isolated-perfused rat heart tissue subjected to as little as 10 min hypoxia and that these changes were not exacerbated by reoxygenation. The mechanism and species specificity of this finding is not known. Rabbit hearts, which lack measurable xanthine oxidase activity, were examined for evidence of hypoxia-induced injury. The release of lactate dehydrogenase into the coronary effluent gradually increased during the retrograde perfusion of isolated rabbit hearts with hypoxic medium (containing 10 mM glucose and 2.5 mM calcium), and was slightly enhanced upon reoxygenation after 60 min hypoxia. Cardiac glutathione content decreased significantly while glutathione disulfide, protein-glutathione mixed disulfides, thiobaribturic acid reactive substances (TBARS), and protein carbonyl contents increased significantly after 60 min of hypoxia, compared to oxygenated controls. These values were unaltered after 4 min of reoxygenation except for a loss of TBARS. The oxidative changes observed in hypoxic rabbit hearts may be caused by energy deficiency impairing normal reductive processes or by the generation of reactive oxygen species as a result of abnormal cell functions, but cannot be related to xanthine oxidase activity.

Animals↗
PubMed1991

[Management of vesicoureteral reflux in patients with neurogenic bladder dysfunction].

We studied 20 cases of neurogenic bladder with vesico-ureteral reflux retrospectively. Seven patients voided with Valsalva's maneuver and 12 patients were managed with clean intermittent catheterization, but one patient required permanent urinary diversion because of uncontrollable urinary tract infection. The patients were followed by intravenous pyelography, radioisotope renogram, voiding cystourethrography, determination of serum creatinine level and urodynamic study. Anti-reflux surgery was performed in 22 ureters and reflux resolved in 19 ureters. Among 12 ureters not treated by anti-reflux surgery, reflux disappeared in 5 ureters and improved in 2 ureters. Of 5 ureters, reflux resolved after clean intermittent catheterization in 2 ureters, and remained stable without recurrent infection or renal deterioration in the remaining 5 ureters. Regardless whether antireflux surgery was done or not, most of the patients who had high grade reflux and obstructive renal damage on radioisotope examinations had marked low compliance bladders. Our experience suggested the necessity of a suitable treatment to improve bladder compliance before considering anti-reflux surgery.

Adolescent↗
PubMed1990

Therapy of chronic hepatitis B with recombinant human alpha and gamma interferon.

Eight patients with chronic hepatitis B entered a pilot study of gamma interferon and alpha interferon in combination. Gamma interferon alone had minimal inhibitory effects on serum levels of hepatitis B virus as monitored by serum HBV DNA and DNA-polymerase activity. The drug also gave troublesome side effects. In contrast, alpha interferon had more potent inhibitory effects on serum HBV levels and fewer side effects. When combined, the two interferons showed no additive or synergistic effects in inhibiting serum levels of HBV DNA or DNA polymerase. These findings indicate that the addition of gamma interferon to alpha interferon provides no additional antiviral effects but contributes significantly to side effects.

Adult↗
PubMed1990

Safety and long-term benefit of carotid endarterectomy in the asymptomatic patient.

In order to determine the safety and long-term salutary effects of carotid endarterectomy in the asymptomatic patient, we retrospectively reviewed all asymptomatic patients who underwent carotid endarterectomy from 1980 through 1986. There were 60 carotid endarterectomies performed in 54 patients, 53 men and one woman. The mean age was 64 years. Arteriography revealed a high grade stenosis of 70% or greater in 46 carotid arteries (77%), ulceration in five (8%), and both in nine (15%). Risk factors included coronary artery disease in 60% of patients, smoking in 87%, hypertension in 67%, and diabetes in 22%. Perioperative morbidity included three cranial nerve injuries, one myocardial infarction and one contralateral stroke. There were no deaths. Mean follow-up was 47 months with only two patients being lost to follow-up. During follow-up three patients suffered ipsilateral transient ischemic attacks without recurrent carotid stenosis and one patient had a transient ischemic attack secondary to contralateral carotid occlusion. There was one ipsilateral stroke occurring two years after operation secondary to restenosis that required reoperation and four late contralateral strokes. Ten patients died in the follow-up period. Causes of death were stroke (1), cardiac (4), malignancy (2), pulmonary (2), and unknown (1). All surviving patients were evaluated by duplex scan at a mean interval following surgery of 47 months. Restenosis of endarterectomized arteries was seen at the following rates: less than 50% in 41 (87%); 50-75% in four (8.5%); 80% in one (2%); and 90% in one (2%). Life table analysis revealed a 98% ipsilateral stroke-free rate at five and eight years.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗