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Biomedical subjects

W S Choi

Publications and source records attributed to W S Choi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of dopamine and melatonin on the regulation of the PIT-1 isotype, placental growth hormone and lactogen gene expressions in the rat placenta.

Rat placenta produces several members of the placental prolactin-growth hormone (PRL-GH), including placental lactogen (PL) and placental prolactin like protein (PLP), during pregnancy. It is important to study placental local regulators that control the expression of PRL-GH genes. We have previously reported that dopamine (DA) can regulate Pit-1 and PL-II gene expressions. In this study we aimed to investigate the local expression of melatonin receptor 1a (Mel1a) and the effects of DA and melatonin on the expressions of PL-Iv, PL-II, PLP-C genes and Pit-1 gene that are involved in the expression of PRL-GH genes in the rat pituitary and placenta. According to the Northern blot analysis, DA receptor 2 (D2) was expressed in the rat placenta. We also report on the local expression of Mel1a in the rat placenta for the first time. Injected DA agonist, bromocriptine (in vivo) decreased PL-Iv, PLP-C and Pit-1 mRNA levels in the rat placenta. The melatonin agonist, chloromelatonin in culture media also decreased the levels of PL-Iv, PL-II and PLP-C mRNA. However, melatonin does not affect the Pit-1 mRNA level. These data suggest that D2 and Mel1a may control the expression of PRL-GH genes in the rat placenta and its response to the extracellular changes of DA and melatonin secreted from the maternal organ. However, Pit-1 may not be involved in the Mel1a induced inhibition of PRL-GH gene expressions in the rat placenta.

Animals↗
PubMed1999

Localization of dopamine D1 and D2 receptor mRNAs in the rat systemic and pulmonary vasculatures.

The present study was designed to evaluate the expression of dopamine D1 and D2 receptor mRNAs in systemic and pulmonary vasculatures. Using specific antisense riboprobes for dopamine D1 and D2 receptor cDNAs, in situ hybridization histochemistry was performed in the aorta, common carotid artery, vertebral artery, pulmonary artery, and superior vena cava of the adult male Sprague Dawley rat. In the case of the aorta, common carotid artery, and vertebral artery, dopamine D1 receptor mRNAs localized mainly in the smooth muscle cells of the tunica media. However, the signals of dopamine D2 receptor mRNAs were found in the endothelium and subendothelial layer of tunica intima, and interstitial cells of tunica adventitia. In the case of the pulmonary artery, signals of dopamine D1 receptor mRNAs were detected within the tunica intima, media, and adventitia. Expression of D2 receptor mRNAs was detected in the walls of small blood vessels within the tunica adventitia of the pulmonary artery. There were no detectable signals of dopamine D1 and D2 receptor mRNAs in the vein. The uneven distribution of dopamine D1 and D2 receptor mRNAs in the rat systemic vasculatures and pulmonary artery suggests that dopamine differentially regulates the vasodilation of the systemic and pulmonary arteries through the differential stimulation of dopamine D1 and D2 receptor.

Animals↗
PubMed1999

Two distinct mechanisms are involved in 6-hydroxydopamine- and MPP+-induced dopaminergic neuronal cell death: role of caspases, ROS, and JNK.

In this study, we examined the possibility that MPTP and 6-hydroxydopamine (6-OHDA) act on distinct cell death pathways in a murine dopaminergic neuronal cell line, MN9D. First, we found that cells treated with 6-OHDA accompanied ultrastructural changes typical of apoptosis, whereas MPP+ treatment induced necrotic manifestations. Proteolytic cleavage of poly-(ADP-ribose)polymerase by caspase was induced by 6-OHDA, whereas it remained uncleaved up to 32 h after MPP+ treatment and subsequently disappeared. Accordingly, 6-OHDA- but not MPP(+)-induced cell death was significantly attenuated in the presence of a broad-spectrum caspase inhibitor, N-benzyloxy-carbonyl-Val-Ala-Asp-fluomethylketone (Z-VAD-fmk). As measured by fluorometric probes, the level of reactive oxygen species (ROS) significantly increased after 6-OHDA treatment. In contrast, the level of dihydroethidium-sensitive ROS following MPP+ treatment remained unchanged while a slight increase in dichlorofluorescin-sentive ROS was temporarily observed. As demonstrated by immunoblot analysis, the level of superoxide dismutase was down-regulated following 6-OHDA treatment, whereas it remained unchanged after MPP+ treatment. Cotreatment of cells with antioxidants such as N-acetylcysteine or Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP, cell-permeable superoxide dismutase mimetic) rescued 6-OHDA- but not MPP(+)-induced cell death, whereas inclusion of catalase or N(G)-nitro-L-arginine had no effect in both cases. In addition, 6-OHDA induced ROS-mediated c-Jun N-terminal kinase (JNK) activation that was attenuated in the presence of N-acetylcysteine or MnTBAP but not catalase or Z-VAD-fmk. In contrast, MPP+ has little effect on JNK activity, indicating that ROS and/or ROS-induced cell death signaling pathway seems to play an essential role in 6-OHDA-mediated apoptosis but not in MPP(+)-induced necrosis in a mesencephalon-derived, dopaminergic neuronal cell line.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Characterization of MPP(+)-induced cell death in a dopaminergic neuronal cell line: role of macromolecule synthesis, cytosolic calcium, caspase, and Bcl-2-related proteins.

To further characterize MPP(+)-induced cell death and to explore the role of Bcl-2-related proteins in this death paradigm, we utilized a mesencephalon-derived dopaminergic neuronal cell line (MN9D) stably transfected with human bcl-2 (MN9D/Bcl-2), its C-terminal deletion mutant (MN9D/Bcl-2Delta22), murine bax (MN9D/Bax), or a control vector (MN9D/Neo). As determined by electron microscopy and TUNEL assay, MN9D/Neo cells exposed to MPP(+) underwent a cell death that was characterized by mitochondrial swelling and irregularly scattered heterochromatin without accompanying DNA fragmentation. However, cell swelling typically seen in necrosis did not appear. To examine the biochemical events associated with MPP(+)-induced cell death, various analyses were conducted. Addition of a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (50-400 microM) or Boc-aspartyl(OMe)-fluoromethylketone (50-200 microM) did not attenuate MPP(+)-induced cell death while the same treatment protected MN9D/Neo cells against staurosporine-induced apoptotic cell death. Concurrent treatment with an inhibitor of macromolecule synthesis such as cycloheximide, emetine, or actinomycin D blocked MPP(+)-induced cell death, suggesting that new protein synthesis is required as demonstrated in many apoptotic cell death. The level of cytosolic calcium in MN9D/Neo cells was unchanged over 24 h following MPP(+) treatment, as monitored by means of the fluorescent probe Fura-2. Western blot analysis indicated that expression level of proapoptotic protein, Bax was not significantly altered after MPP(+) treatment. In this death paradigm, overexpression of Bcl-2 but not its C-terminal deletion mutant attenuated MPP(+)-induced cell death whereas overexpression of Bax had no effect. Taken together, these data indicate that (i) MPP(+) induces a distinct form of cell death which resembles both apoptosis and necrosis; and (ii) full-length Bcl-2 counters MPP(+)-induced morphological changes and cell death via a mechanism that is dependent on de novo protein synthesis but independent of cytosolic calcium changes, Bax expression, and/or activation of caspase(s) in MN9D cells.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Does parental smoking cessation discourage adolescent smoking?

BACKGROUND: We examined the relationship of smoking cessation in parents to smoking and uptake and cessation by their adolescent children. METHODS: We analyzed a cross-sectional sample of 4,502 adolescents, ages 15-17 years, who lived in two-parent households that were interviewed as part of the 1992-1993 Tobacco Supplement of the Current Population Survey, which questioned householders 15 years of age and older about their smoking history. Ever smokers reported smoking at least 100 cigarettes in their lifetime. Former smokers were ever smokers who had quit. RESULTS: Multivariate analyses, adjusted for demographic characteristics of adolescents, as well as father's age, education, and family income, found that adolescents whose parents had quit smoking were almost one-third less likely to be ever smokers than those with a parent who still smoked. Furthermore, adolescent ever smokers whose parents quit smoking were twice as likely to quit as those who had a parent who still smoked. Parental quitting is most effective in reducing initiation if it occurs before the child reaches 9 years of age. CONCLUSION: Encouraging parents to quit may be an effective method for reducing adolescent smoking, through decreased uptake and increased cessation. The earlier parents quit, the less likely their children will become smokers.

Adolescent↗
PubMed1999

Predictors of smoking cessation in U.S. adolescents.

OBJECTIVE: To identify factors that predict quitting among adolescent smokers. METHODS: Adolescent smokers aged 12-19 years (N = 633) from the national Teenage Attitudes and Practices Survey I (1989), were followed up in the Teenage Attitudes and Practices Survey II (1993). Multiple logistic regression was applied to identify the predictors of quitting. RESULTS: A total of 15.6% of adolescent smokers had quit smoking at the follow-up survey four years later. There was no significant difference in the quit rate by age, gender, or ethnicity. Five baseline factors were identified in a multivariate analysis as significant predictors of quitting: frequency of smoking, length of past quit attempts, self-estimation of likelihood of continuing smoking, mother's smoking status, and depressive symptoms. The more risk factors the adolescents had, the less likely they would succeed in quitting. CONCLUSIONS: Quitting smoking by adolescents is influenced by multiple biological, behavioral, and psychosocial variables. Identifying these variables can help tailor cessation programs to more effectively help adolescents quit smoking.

Adolescent↗
PubMed1999

Synthesis and evaluation of amino acid esters of 6-deoxypenciclovir as potential prodrugs of penciclovir.

The amino acid ester derivatives of 6-deoxypenciclovir, 11-20, were synthesized as potential prodrugs of penciclovir, and were evaluated for their oral penciclovir bioavailability in mice and rats. Esterification of 6-deoxypenciclovir with N-carbobenzyl-oxyglycine, -L-alanine, -L-valine, -L-leucine, or -L-isoleucine (3.75equiv.) using conventional coupling method (DCC/DMAP) afforded the mono-O-ester derivatives 1-5 in 47-55% yields as a mixture of two diastereomers along with the di-O-ester derivatives 6-10 in 20-29% yields. Reductive cleavage of carbobenzyloxy (Cbz) group (10% Pd/C, 1 atmosphere of H2, room temperature in methanol) followed by subsequent treatment of the resulting free amine with methanolic HCI solution provided the mono-O-ester derivatives 11-15 as di-HCl salt in 51-98% yields and the di-O-ester derivatives 16-20 as tri-HCl salt in 65 98% yields. Of the prodrugs tested in mice and rats, 6-deoxypenciclovir O-L-valinate (13), O-L-isoleucinate (15), and O,O-di-glycinate (16) showed significantly higher urinary recovery of penciclovir compared with that of penciclovir, but those are somewhat lower than that of famciclovir.

Acyclovir↗
PubMed1999

Synthesis and evaluation of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines and 2-amino-9-(3-alkoxycarbonyloxymethyl-4-alkoxycarbonyloxybut-1- yl)purines as potential prodrugs of penciclovir.

A series of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purin es (1-8) and 2-amino-9-(3-alkoxycarbonyl-oxymethyl-4-alkoxycarbonyloxybut -1-yl)purines (9-12) were synthesized as potential prodrugs of penciclovir. Treatment of 6-deoxypenciclovir with trimethyl orthoacetate or triethyl orthopropionate (1.2 equiv) in DMF in the presence of p-TsOH.H2O (0.1 equiv) followed by quenching with excess H2O gave the corresponding mono-O-acetyl or mono-O-propionyl compound, 17 or 18, in excellent yields of 95 and 92%, respectively. Reactions of 17 or 18 with an appropriate alkyl (Me, Et, n-Pr, and i-Pr) 4-nitrophenyl carbonate (1.2 equiv) in pyridine in the presence of a catalytic amount of DMAP (0.1 equiv) at 80 degrees C afforded the monoacyl, monocarbonate derivatives of 6-deoxypenciclovir, 1-8, in 86 94% yields. Similar reactions of 6-deoxypenciclovir with 2.1 equiv of alkyl 4-nitrophenyl carbonate produced the dicarbonate derivatives 9 12 in 81-83% yields. Of the prodrugs tested in rats, 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (4) achieved the highest mean urinary recovery of penciclovir (36%), followed in order by compounds 2 (35%), 6 (35%), 7 (34%), 10 (34%), 8 (32%), 3 (32%), and famciclovir (31%). The mean urinary recovery of penciclovir and concentrations of penciclovir in the blood from 4 in mice were also slightly higher than those from famciclovir. The in vivo antiviral efficacy of 4 in HSV-1-infected normal BALB/c mice was higher than those of famciclovir and valaciclovir in terms of mortality (100, 80, and 40%) and mean survival time ( > 21, 13+/-5.0 (SEM), and 13+/-1.6 days). Compound 4 demonstrated an effective anti-hepadnaviral response with intrahepatic viral load being reduced by 90%, the viral supercoiled DNA levels reduced by 70% and Pre-S expression inhibited by 30% against duck hepatitis B virus (DHBV) in vivo, and did not cause any significant hepatotoxicity after 4 weeks of treatment.

Acyclovir↗
PubMed1999

How many adolescents start smoking each day in the United States?

PURPOSE: To provide daily estimates of first experimentation and attainment of established smoking in adolescents 11-17 years of age. METHODS: The 1989 and 1993 Teenage Attitudes and Practices Surveys (TAPS) (16,954 observations) was used to estimate rates in 1991 for: (a) first experimentation (even a few puffs), and (b) established smoking (reaching a lifetime level of at least 100 cigarettes). The 1992 and 1993 Current Population Surveys (CPS) (82,279 adults) allowed calculation of year-specific initiation rates (1980-1989) from the age respondents reported as having started smoking "fairly regularly." Rates were applied to Census data for the appropriate years to yield numbers accruing each day. Estimates were calculated for adolescents (11- to 17-year-olds) and youth (11- to 20-year-olds). RESULTS: For TAPS, in 1991, 4824 adolescents first tried cigarettes and 1975 became established smokers each day. Considering all youth, these estimates increase to 5497/day for first experimentation and to 2933/day for established smokers. For CPS, from 1980 to 1989, around 2300 adolescents initiated fairly regular smoking each day. For all youth, the estimate has increased to about 3400/day. CONCLUSIONS: Because approximately 4800 adolescents and 5500 youth appear to be experimenting with cigarettes for the first time each day, and close to 3000 youth become established smokers daily, increased prevention efforts are clearly justified.

Adolescent↗
PubMed1999

A hybrid bovine beta-casein/bGH gene directs transgene expression to the lung and mammary gland of transgenic mice.

We investigated spatial and temporal expression of bGH controlled by two different sizes (1.8 kb and 15 kb) of 5'-flanking sequences of the bovine beta-casein in transgenic mice. In the 1.8-kb promoter-containing mice, bGH expression was specifically confined to lung and mammary gland at lactation. While mammary gland expression was highly variable depending on the lines, lung expression was relatively constant with a high level in most lines. Moreover, this dual-tissue specificity of bGH expression was consistently retained in all of the 15 kb-promoter-containing mice, although a low ectopic expression was sometimes detected in salivary gland or brain. During mammary gland development in the 1.8-kb promoter-containing mice was mammary gland expression first detected at lactation, following the bovine rather than murine pattern of beta-casein expression. In contrast, lung expression was almost constant regardless of mammary gland developmental state or sex. Therefore, it can be concluded that a combination of the bovine beta-casein promoter and bGH gene directs a distinct dual-tissue specific bGH expression with different regulatory mechanisms between mammary gland and lung and as little as 1.8-kb promoter is sufficient for the proper regulation of the bovine beta-casein gene in mammary gland.

Animals↗
PubMed1999

Sequential cleavage of poly(ADP-ribose)polymerase and appearance of a small Bax-immunoreactive protein are blocked by Bcl-X(L) and caspase inhibitors during staurosporine-induced dopaminergic neuronal apoptosis.

To assess the role of Bcl-X(L) and its splice derivative, Bcl-X(S), in staurosporine-induced cell death, we used a dopaminergic cell line, MN9D, transfected with bcl-xL (MN9D/Bcl-X(L)), bcl-xS (MN9D/Bcl-X(S)), or control vector (MN9D/Neo). Only 8.6% of MN9D/Neo cells survived after 24 h of 1 microM staurosporine treatment. Caspase activity was implicated because a caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk), attenuated staurosporine-induced cell death. Bcl-X(L) rescued MN9D cells from death (89.4% viable cells), whereas Bcl-X(S) had little or no effect. Bcl-X(L) prevented morphologically apoptotic changes as well as cleavage of poly(ADP-ribose)polymerase (PARP) induced by staurosporine. It is interesting that a small Bax-immunoreactive protein appeared 4-8 h after PARP cleavage in MN9D/Neo cells. The appearance of the small Bax-immunoreactive protein, however, may be cell type-specific as it was not observed in PC12 cells after staurosporine treatment. The sequential cleavage of PARP and the appearance of the small Bax-immunoreactive protein in MN9D cells were blocked either by Z-VAD-fmk or by Bcl-X(L). Thus, our present study suggests that Bcl-X(L) but not Bcl-X(S) prevents staurosporine-induced apoptosis by inhibiting the caspase activation that may be directly or indirectly responsible for the appearance of the small Bax-immunoreactive protein in some types of neurons.

Animals↗
PubMed1999

The social costs of tobacco advertising and promotions.

Recent longitudinal evidence suggests that approximately 34% of all new tobacco experimentation occurs because of tobacco advertising and promotions. Based on this figure, in this paper we estimate the long-term impact on mortality and morbidity, as well as the economic and medical costs associated with smoking that is attributable to cigarette advertising and promotions in the United States. This study used several data sources, including the Teenage Attitudes and Practices Survey (TAPS), the 1993 and 1996 Adolescent California Tobacco Surveys (CTS), and the Food and Drug Administration's estimates of annual illness-related benefits of alternative effectiveness rates of banning tobacco advertising. Our resulting estimates are that in each year between 1988 and 1998, tobacco advertising and promotional activities generated approximately 193000 additional adult smokers who began smoking as adolescents because of advertisements and promotions. That decade of tobacco advertising and promotions will also result in approximately 46400 smoking-attributable deaths per year and 698400 years of potential life lost, which translates into costs of approximately $21.7 billion to $33.3 billion in total medical, productivity, and mortality-related costs. Even accounting for quitting behavior, each year of advertising-attributable smoking increases the number of smokers in the population. We conclude that annual costs can be expected to continue to increase if tobacco advertising and promotional activities are not effectively eliminated. If all tobacco industry advertising and promotional activities were banned for the next 25 years, nearly 60000 smoking-attributable deaths per year could be avoided, saving nearly 900000 life-years, $2.6 billion in excess medical expenses, and between $28 billion and $43 billion in mortality costs.

Adolescent↗
PubMed1999

Purification and characterization of a novel dipeptidyl peptidase from Dictyostelium discoideum.

A dipeptidyl peptidase (DPP) was purified to homogeneity using lys-ala-beta-naphthylamide, the standard substrate for DPP II. The enzyme is a monomer with a Mr of 70kDa, pl 5.2, and Km 5.0 microM. Its terminal amino acid sequence was XXLLYAIQKRLF and was not identical to that of any known protein. Although initially considered to be a DPP II, the enzyme differed in some properties from classical DPP IIs. It had a pH optimum of 7.9, was not active on X-pro-naphthylamides, the usual substrates of mammalian DPP II, but was active on arg-arg- and asp-arg-naphthylamides, substrates acted on by the DPP III class of enzymes. This enzyme therefore combines properties typical of both DPP II and III and differs from all previously described DPPs. Activity on lys-ala-beta-naphthylamide was most abundant during aggregation and its activity is consistent with processing specific peptides during development.

Aminopeptidases↗
PubMed1999

Sharing the blame: smoking experimentation and future smoking-attributable mortality due to Joe Camel and Marlboro advertising and promotions.

BACKGROUND: Despite public denials, internal tobacco company documents indicate that adolescents have long been the target of cigarette advertising and promotional activities. Recent longitudinal evidence suggests that 34% of new experimentation occurs because of advertising and promotions. OBJECTIVE: To apportion responsibility for smoking experimentation and future smoking-attributable mortality among major cigarette brands attractive to young people (Camel and Marlboro). DATA SOURCES, SETTING, AND PARTICIPANTS: Data were from confirmed never-smoking adolescents (12-17 years old) responding to the 1993 (n = 2659) and 1996 (n = 2779) population-based California Tobacco Surveys. MAIN OUTCOMES: Adolescents named the brand of their favourite cigarette advertisements and tobacco promotional items. Using these "market shares" and the relative importance of advertising and promotions in encouraging smoking, we estimated how many new experimenters from 1988 to 1998 in the United States can be attributed to Camel and Marlboro. From other data on the natural history of smoking, we projected how many future deaths in the United States can be attributed to each brand. RESULTS: Although Camel advertisements were favoured more than Marlboro and other brands in 1993 and 1996, the "market share" for promotional items shifted markedly during this period from Camel and other brands towards Marlboro. We estimated that between 1988 and 1998, there will be 7.9 million new experimenters because of tobacco advertising and promotions. This will result in 4.7 million new established smokers: 2.1, 1.2, and 1.4 million due to Camel, Marlboro, and other brands' advertising and promotions, respectively. Of these, 1.2 million will eventually die from smoking-attributable diseases: 520,000 from Camel, 300,000 from Marlboro, and the remainder from other brands. CONCLUSIONS: Our analysis provides a reasonable first estimate at sharing the blame for the long-term health consequences of smoking among the major brands that encourage adolescents to start smoking.

Adolescent↗
PubMed1999

Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide with considerable homology to vasoactive intestinal peptide and GH-releasing hormone, exists in two biologically active forms, PACAP-38 and -27. The presence of PACAP in the ovary has been demonstrated, where it stimulates steroidogenesis and cAMP accumulation in cultured granulosa cells. In the present study, gonadotropin regulation of PACAP gene expression was examined in PMSG/human (h)CG-treated immature rat ovaries and cultured preovulatory follicles. Northern blot analysis of ovaries obtained from PMSG/hCG-treated immature animals revealed the transient induction of PACAP transcripts by hCG, reaching a maximum at 6 h. The major cell types expressing PACAP messenger RNA were granulosa cells of preovulatory follicles and some theca/interstitial cells. In preovulatory follicles cultured in serum-free medium, PACAP transcripts were transiently induced by LH and FSH, reaching a maximum 6-9 h after stimulation in granulosa cells but not in theca cells. Treatment with cycloheximide or alpha-amanitin abolished LH-induced PACAP transcripts, indicating that new protein synthesis and transcription are necessary. Treatment with MDL-12,330A, an inhibitor of adenylate cyclase, inhibited LH-induced PACAP messenger RNA, and forskolin mimicked the LH action, implying the role of adenylate cyclase activation. In contrast, treatment with chelerythrine, an inhibitor of protein kinase C, and 2-O-tetradecanol-phorbol-13-acetate had no effect. We further tested the role of PACAP in follicle apoptosis using apoptotic DNA fragmentation analysis. Treatment with PACAP-38 suppressed follicle apoptosis in a dose-dependent manner. Moreover, the LH suppression of follicle apoptosis was partially blocked by cotreatment with PACAP-38 antagonist, indicating mediation by endogenous PACAP-38. These results suggest that PACAP, transiently induced by the gonadotropin surge, could be a local regulator of a number of events and may act as a follicle survival factor during the periovulatory period.

Adenylyl Cyclases↗
PubMed1999

Biochemical and pharmacological characteristics of a newly synthesized H+/K+-ATPase inhibitor, YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, in pigs and rats.

We have investigated the effect of the newly synthesized proton-pump inhibitor YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid secretion and gastric lesions in experimental animals. In lyophilized pig gastric microsomes, YJA20379-8 was shown to inhibit H+/K+-ATPase activity; the inhibitory effect was not affected by pH, the IC50 (dose resulting in 50% inhibition) being 28.0 microM and 30.0 microM at pH 6.4 and pH 7.4, respectively. The effect was fully reversed by dilution and subsequent washing of the incubation mixtures of H+/K+-ATPase and YJA20379-8, suggesting the reversible nature of the enzyme inhibition. In pylorus-ligated rats, YJA20379-8 administered by different routes (intraduodenal, subcutaneous, intravenous or oral) resulted in dose-dependent suppression of basal gastric acid secretion. The duration of antisecretory action of 30 mg kg(-1) YJA20379-8 given intraduodenally was very brief (less than 7 h). Pretreatment with YJA20379-8 also dose-dependently prevented gastric lesions induced by absolute ethanol and water-immersion stress in rats. These results suggest that YJA20379-8 might exert its antiulcer activity partly by reversible suppression of acid secretion and partly by protecting the gastric mucosa against ulcerative stimuli.

Animals↗
PubMed1999

Multifocal meningioangiomatosis: a report of two cases.

We report the CT and MR findings in two patients with multifocal meningioangiomatosis, neither of whom had a family history or stigmata of neurofibromatosis. All lesions were located in the cortical and subcortical areas and had round dense calcifications with eccentric cysts. The masses were associated with surrounding edema and gliosis.

Angiomatosis↗