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Biomedical subjects

Y Park

Publications and source records attributed to Y Park.

At least 235 records · Page 13Linked to original sources

Protection against hypoxic injury in isolated-perfused rat heart by ruthenium red.

Changes in intracellular calcium content and energy production during the period of hypoxia appear to be necessary for the development of cellular injury. Ruthenium red, a hexavalent dye which inhibits the active uptake of calcium by mitochondria, might improve a cell's energy status thereby minimizing hypoxic injury. Rat heart tissue was perfused retrogradely with Krebs-Henseleit medium containing 2.5 mM calcium and 10 mM glucose. The infusion of 0.1, 1.0 or 1.24, but not 0.01 microM, ruthenium red throughout 60 min of hypoxia and 30 min of reoxygenation decreased, in a dose-dependent manner, the release of lactate dehydrogenase normally seen at reoxygenation. When the infusion of 1.24 microM ruthenium red was begun after 45 min of hypoxia, lactate dehydrogenase release at reoxygenation after 60 min of hypoxia was decreased, but to a lesser extent than when this agent was present throughout hypoxia. Ruthenium red, 1.24 microM, had no significant effects on coronary flow or function in oxygenated heart tissue. When present throughout hypoxia and reoxygenation, 1.24 microM ruthenium red prevented the decrease in coronary flow normally seen and allowed recovery of heart rate, +dP/dT, -dP/dT and work (defined as the product of developed pressure and heart rate) to normal levels. Significant functional protection was not evident at reoxygenation when ruthenium red was infused after 45 min of hypoxia or in the absence of glucose. Cardiac ATP, creatine phosphate and energy charge were decreased after 60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glomerulonephritis caused by chronic hepatitis B virus infection: treatment with recombinant human alpha-interferon.

STUDY OBJECTIVES: To assess the efficacy of alpha-interferon therapy in patients with hepatitis B virus (HBV)-related glomerulonephritis. DESIGN: Prospective, nonrandomized study. PATIENTS: Five patients with persistence of hepatitis B surface antigen, hepatitis B e antigen (HBeAg) and HBV DNA in serum for at least 6 months and histologic changes of chronic hepatitis on liver biopsy as well as persistent proteinuria of greater than 2 g/d and histologic changes of glomerulonephritis on renal biopsy. INTERVENTIONS: Patients received a 4-month course of recombinant human alpha-interferon (alfa-2b) beginning at a dose of 5 million units administered subcutaneously each day. RESULTS: Serum levels of HBV DNA decreased in all patients and fell to undetectable levels during treatment in four of five patients. In the four responding patients, serum HBeAg disappeared, aminotransferases fell into the normal range, and a follow-up liver biopsy showed an improvement in the hepatocyte necrosis and inflammation. Urine protein excretion also decreased during treatment. In the four responding patients, urine protein excretion gradually fell to less than 1 g/d and serum albumin levels rose into the normal range. Resolution of the biochemical and serologic evidence of chronic hepatitis and glomerulonephritis was accompanied by disappearance of signs and symptoms of liver and kidney disease. CONCLUSIONS: A high proportion of patients with HBV-related glomerulonephritis will respond to a 4-month course of alpha-interferon with a clinical, biochemical, and serologic remission.

Adult↗

Progesterone increases messenger ribonucleic acid (mRNA) encoding luteinizing hormone releasing hormone (LHRH) level in the hypothalamus of ovariectomized estradiol-primed prepubertal rats.

In order to investigate the mechanism underlying ovarian steroid action on gene expression of hypothalamic luteinizing hormone releasing hormone (LHRH), changes in LHRH mRNA level were determined by RNA-blot hybridization assay. Twenty-eight-day-old female rats were ovariectomized (OVX) and implanted with Silastic capsule containing either 17 beta-estradiol (E) or vehicle (V). Two days later (day 30), OVX + E-primed rats were given s.c. progesterone (P, 1 mg) 6 h prior to decapitation. Four experimental groups were studied: (1) intact, (2) OVX + V, (3) OVX + E, and (4) OVX + E + P-treated rats. Poly(A) RNA fractions from hypothalami (40-50/group) were isolated, blotted onto nitrocellulose paper and hybridized with 32P-end-labeled LHRH oligonucleotides (29 mer) which are complementary to rat LHRH mRNA. The hypothalamic LHRH mRNA signal markedly attenuated 2 days following ovariectomy. E replacement to OVX rats slightly increased LHRH mRNA level, which is lower than that of the intact group. However, a single injection of P to OVX + E-treated rats notably augmented the LHRH mRNA level over that observed in the intact group. In addition, LHRH content and release in vitro were examined to correlate with changes in LHRH gene expression. Ovariectomy and the replacement of E and/or P resulted in a similar fashion of changes in LHRH release and content as compared to alteration of LHRH mRNA level. This study clearly demonstrates that P increases LHRH mRNA level in the hypothalamus of OVX + E-primed immature rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevention of acetaminophen-induced hepatotoxicity by dimethyl sulfoxide.

Dimethyl sulfoxide (DMSO) has previously been shown to protect against acetaminophen (APAP)-induced hepatotoxicity, but the mechanism of this effect was not clear. Treatment of mice with 1 mg/kg DMSO 4 h before 250 mg/kg APAP resulted in significantly less hepatotoxicity than with APAP alone, as measured by serum glutamic pyruvic transaminase (SGPT) content 24 h after APAP. Protection was also evident when 1 ml/kg DMSO was given 4, but not 8 h after 250 mg/kg APAP. The APAP-induced depletion of liver glutathione was prevented in mice pretreated with DMSO, although DMSO alone had no effect on liver glutathione levels. The hepatic concentration of cytochrome P-450 (P450) 4 h after treatment of mice with 1 ml/kg DMSO, was significantly decreased compared to saline-treated animals. However, while this DMSO pretreatment significantly decreased the activity of cytochrome P-450-linked aminopyrine-N-demethylase, it increased the activity of aniline hydroxylase. Covalent binding of [14C]APAP to hepatic protein in vivo was significantly decreased in mice pretreated with DMSO. Covalent binding of [14C]APAP to hepatic microsomal protein in vitro was not significantly altered after in vivo treatment with DMSO. However, the presence of DMSO in the in vitro incubation mixture significantly decreased covalent binding of [14C]APAP in a dose-dependent manner compared to microsomal fractions from untreated, saline-treated or DMSO pretreated animals. These data suggest that the DMSO-induced alterations in cytochrome P-450 content and activity may not be the cause of the observed protective action of this chemical. The ability to competitively inhibit APAP bioactivation or to directly scavenge free radicals produced during APAP metabolism, including the activated species which covalently binds to protein, may account for the hepatoprotection afforded by DMSO.

Acetaminophen↗

Testosterone stimulates LH-RH-like mRNA level in the rat hypothalamus.

To elucidate whether testosterone (T) replacement to castrated male rats may promote luteinizing hormone-releasing hormone (LH-RH) biosynthesis in the hypothalamus, an RNA-blot hybridization assay was employed. Poly(A) mRNA fractions from hypothalami (40-50) of intact, castrated plus vehicle, and castrated plus T group were isolated, blotted on nitrocellulose paper and hybridized with 32P-end labelled LH-RH oligonucleotides (29 mer) which is complementary to the rat LH-RH mRNA. LH-RH-like mRNA level markedly attenuated 2 weeks following castration and T replacement significantly increased LH-RH-like mRNA level, comparable to about 80% of that observed in intact male rats. In addition, LH-RH contents and release from hypothalami were studied, to examine the correlation with LH-RH gene expression and secretory activity of LH-RH. Castration significantly reduced LH-RH contents and LH-RH release in vitro. T replacement restored LH-RH contents and release comparable to those shown in the intact group. This study demonstrates for the first time that T replacement increases LH-RH-like mRNA level in the hypothalami of castrated rats suggesting that T may act at the pretranslational level. This change in LH-RH gene expression is parallel with alteration of LH-RH content and release.

Animals↗

Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B.

Forty-five patients with chronic hepatitis B were entered into a randomized controlled trial of recombinant human alpha-interferon therapy. All patients had hepatitis B surface antigen in serum for at least 1 yr and had stable serum levels of both hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen. During the 4-mo period of therapy, 10 of 31 (32%) treated patients and only 1 of 14 (7%) control patients became negative for serum hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase. All 10 patients who became negative for serum hepatitis B virus deoxyribonucleic acid subsequently had a marked improvement in serum aminotransferase activities and lost hepatitis B e antigen from serum, and 9 of them had improvement in liver histology. Comparison of responders to nonresponders indicated that female sex and a high initial level of serum aspartate aminotransferase correlated best with response to interferon therapy. These findings indicate that a 4-mo course of recombinant alpha-interferon can induce a remission in disease in approximately one-third of patients with chronic hepatitis B.

Adolescent↗

Arteriovenous malformation of the maxillary sinus: an unusual clinical presentation.

Arteriovenous (AV) malformation is a rare vascular lesion of the jaws with a benign clinical presentation. As a result, AV malformation may be excluded from a presurgical differential diagnosis, with catastrophic results. Review of the pertinent literature showed no documentation of AV malformation in the maxillary sinus, and therefore we present the case of a 43-year-old white man with a history of blunt trauma to the paranasal region, whose differential diagnosis included a vascular lesion.

Adult↗

Effect of coix on plasma, liver, and fecal lipid components in the rat fed on lard- or soybean oil-cholesterol diet.

To determine the influence of dietary coix on lipid metabolism, the effect of coix on plasma, liver, and fecal lipid components was studied using Sprague-Dawley male rats. All rats were divided into four groups, and the rats of each group were fed the coix-lard diet, coix-soybean oil diet, or the respective control diets (containing 1% cholesterol each) for 27 days. Plasma and liver cholesterol levels in the coix-lard diet group significantly decreased as compared with those in the control group, whereas there was no effect on the fecal excretion of cholesterol. The decreases in the concentrated liver triglyceride and the increases in the fecal excretion of triglyceride were found in coix-soybean oil diet group. Moreover, liver and fecal phospholipid levels in both coix diet groups significantly increased. But there were no significant changes in plasma and fecal bile acids in either coix diet group. These results suggest the possibilities that coix may have an inhibitory action on cholesterol synthesis in liver, a facilitating effect on biliary excretion of triglyceride, and an acceleratory action on phospholipid synthesis in liver.

Animals↗

Medical adrenalectomy for advanced prostatic cancer: clinical and hormonal effects.

We examined the effect of medical adrenalectomy on the clinical and hormonal responses in 50 men with disseminated prostatic carcinoma. Patients refractory to initial hormonal therapy were treated with aminoglutethimide and hydrocortisone (AG-HC) and evaluated by the criteria of the National Prostatic Cancer Project. Eight patients showed a partial response (PR), and 17 remained stable while receiving these medications. Survival times for these two groups averaged 87.8 and 38 weeks, respectively. In contrast, 17 men were unresponsive to this therapy, exhibiting progressive disease with a mean survival time of 18 weeks. Eight patients could not tolerate the drug regimen or were lost to follow-up. Serum and urinary hormone profiles determined serially during AG-HC therapy revealed that all measured serum androgens and estrogens were significantly lowered by AG-HC treatment; however, specific hormones, including free testosterone, dihydrotestosterone, estrone, and estradiol were suppressed to a greater degree in responders (R) as compared with nonresponders (NR). Urinary excretion of 17-ketosteroids did not change during AG-HC therapy, but specific androgen metabolites, including testosterone glucuronide and androstanediol glucuronide, were suppressed by 50% during AG-HC therapy. We showed modest clinical benefit of AG-HC therapy in advanced prostatic cancer. That greater hormonal suppression was associated with greater responsiveness to this therapy raises the hope that further manipulations directed against suppression of extratesticular androgens may be a useful approach as second-line treatment of advanced prostatic cancer.

Aged↗

Energy dependence of enzyme release from hypoxic isolated perfused rat heart tissue.

There is a sudden release of intracellular constituents upon reoxygenation of isolated perfused hypoxic heart tissue (O2 paradox) or on perfusion with calcium-free medium after a period of hypoxia. Rat hearts were perfused by the method of Langendorff (Pfluegers Arch. 61: 291-332, 1895) with Krebs-Henseleit medium containing 10 mM glucose. Hearts were equilibrated for 30 min, followed by 90 min of hypoxia or 60 min of hypoxia and 30 min of reoxygenation. The massive enzyme release observed upon reoxygenation after 60 min of hypoxia was prevented by infusing 0.5 or 5 mM cyanide 5 min before reoxygenation. Lactate dehydrogenase (LDH) release commenced immediately upon withdrawal of cyanide. Hearts perfused with calcium-free medium throughout hypoxia did not release increased amounts of LDH at reoxygenation. Perfusing heart tissue with medium containing 0 or 25 microM calcium, but not 0.25 or 2.5 mM, after 50 min of hypoxia initiated a release of cardiac LDH, which was not further enhanced by reoxygenation. Enzyme release was significantly inhibited when the calcium-free perfusion medium included 10 mM 2-deoxyglucose (replacing glucose), 0.5 mM dinitrophenol, or 2.5 mM cyanide. Histologically, hearts perfused with calcium-free medium after 50 min of hypoxia showed areas of severe necrosis and contracture without any evidence of the contraction bands that were seen in hearts reoxygenated in the presence of calcium. Cardiac ATP and creatine phosphate (PCr) levels were significantly decreased after 50-60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Psychiatric complications of long-term interferon alfa therapy.

Ten (17%) of 58 patients with chronic viral hepatitis treated with a four- to 12-month course of recombinant human interferon alfa developed psychiatric side effects. The psychiatric side effects fell into three categories: an organic personality syndrome characterized by irritability and short temper; an organic affective syndrome marked by extreme emotional lability, depression, and tearfulness; and a delirium marked by clouding of consciousness, agitation, paranoia, and suicidal potential. These psychiatric side effects appeared after one to three months of therapy, usually improved within three to four days of decreasing the dose of interferon alfa, and invariably resolved once therapy was stopped. The organic personality and affective syndromes tended to occur in patients who received the highest dose of interferon alfa, who had relatively mild hepatitis, and who lost weight during interferon treatment. Delirium tended to occur in patients with severe hepatitis who had previous evidence of organic brain injury or dysfunction or previous drug and alcohol abuse. Failure to recognize these side effects quickly and to treat them with supportive therapy and modification of the dose of interferon alfa could result in limitation of therapy and serious personal and interpersonal consequences.

Adult↗

Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report.

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.

Adult↗