Search PubMed⌕ Search

Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 217 records · Page 12Linked to original sources
PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.

The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.

Animals↗
PubMed1997

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry with delayed ion extraction to ganglioside analyses.

Various monosialo- and disialo-gangliosides and their derivatives were examined by delayed ion extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF MS) in the reflector mode with alpha-cyano-4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid used as the matrix. Native gangliosides were generally found to give good spectra in the negative ion mode. 2,5-Dihydroxybenzoic acid was a better matrix for gangliosides than alpha-cyano-4-hydroxycinnamic acid, because this matrix seemed to minimize loss of sialic acid and carbon dioxide of gangliosides. About 1 pmol of ganglioside was able to be detected with this matrix. When "A-series" gangliosides such as GD1a and GalNAc-GD1a gave undesirable extra peaks probably due to loss of sialic acid besides molecule-related ion peaks, the methyl-esterification of the gangliosides at the carboxyl groups of sialic acids was found to be necessary to obtain good DE MALDI-TOF mass spectra in the positive ion mode. In contrast, "B-series" gangliosides such as GD1b, GD2, and GD3 gave rise to major dehydrated molecule-related ion [M-H2O-H]- peaks in the negative ion mode without the pretreatment of methyl-esterification. The DE MALDI-TOF mass spectrometric analysis enabled us to distinguish between GD1a and GD1b, which have the same molecular weight. It was also found that not only a purified sample, but also a mixed sample of various gangliosides was amenable to the identification of them by DE MALDI-TOF MS.

Carbohydrate Conformation↗
PubMed1997

Preparation of various lysogangliosides including lyso-fucosyl GM1 and delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis.

Our rapid method of microwave-mediated saponification for preparing lysoglycosphingolipids from their parent glycosphingolipids was also able to prepare lysogangliosides or modified lysogangliosides, which were identified by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometric (DE MALDI-TOF MS) analysis. When GM3, GM2, and GM1 isolated from adult human brain gangliosides were subjected to the saponification, GM3 was found to give rise to only lyso-GM3 containing de-N-acetylneuraminic acid (de-N-acetyl lyso-GM3), whereas the GM2 produced both lyso-GM2 and the de-N-acetyl compound, and GM1 also gave both lyso-GM1 and the de-N-acetyl compound. In the saponification of GM1 and GDla, isolated from rat brain gangliosides, GM1 similarly produced both lyso-GM1 and the de-N-acetyl compound, but GDla was found to give rise to both dehydrated de-N-monoacetyl and dehydrated de-N-diacetyl lyso-GDla. However, the saponification of the GM1 fraction isolated from porcine brain gangliosides gave rise not only to both lyso-GM1 and the de-N-acetyl compound, but also unexpectedly to both lyso-fucosyl GM1 and its de-N-acetyl compound. The untreated GM1 fraction was examined by TLC and DE MALDI-TOF mass spectrometry, and proved to contain fucosyl-GM1. The DE MALDI-TOF MS analysis of the prepared lyso-gangliosides showed that their long chain bases consisted of d18:1 and d20:1 sphingosines in various ratios reflecting those of the different mammalian brain gangliosides.

Adult↗
PubMed1997

Inhibitory effect of NS-398, a selective cyclooxygenase-2 inhibitor, on azoxymethane-induced aberrant crypt foci in colon carcinogenesis of F344 rats.

Prostaglandin E2, which is produced by cyclooxygenase (COX) during arachidonic acid metabolism, is considered to be related to colon carcinogenesis. Therefore, the effect of NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide), a COX-2 inhibitor, was examined in azoxymethane (AOM)-induced colon carcinogenesis in rats in this study. In the first experiment, groups 1-3 were treated with AOM (15 mg/kg, s.c.) 3 times at intervals of a week from 5 weeks of age. Groups 2 and 3 were respectively given 1 mg/kg and 10 mg/kg of NS-398 in 5% gum arabic aqueous solution 3 times per week by oral gavage during the experiment. Six weeks after the first exposure to AOM, aberrant crypt foci (ACF) were counted in the colonic mucosa of all rats. The mean occurrence of ACF per length in rats given 1 mg/kg b.w. or 10 mg/kg b.w. of NS-398 was reduced to 65.7% or 52.8%, respectively, of that in rats treated with only AOM. Levels of COX-2 mRNA expression in groups treated with AOM, regardless of NS-398, were slightly higher than that in the group treated with NS-398 alone as judged from reverse transcription-polymerase chain reaction analysis. In the second experiment, the effect of NS-398 at different times, i.e., during initiation and post-initiation, was examined. Treatment with NS-398 in both phases significantly inhibited the appearance of ACF. The results imply that NS-398 might have a chemopreventive potential.

Animals↗
PubMed1997

Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines.

Recent studies have suggested that apoptosis is a key phenomenon in the chemopreventive action of nonsteroidal antiinflammatory drugs (NSAIDs), which exhibit cancer-preventive and tumor-regressive effects in the human colon. The effect of NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide, which is a selective inhibitor of cyclooxygenase-2 (COX-2), on the induction of apoptosis in two human colorectal cancer cell lines (Colo320 and THRC) was determined. The apoptotic ratios (-fold vs. control value) of Colo320 in the presence of 100 microM indomethacin and NS-398 were 3.3 +/- 1.5 and 9.0 +/- 0.94, and those of THRC were 2.3 +/- 0.46 and 7.4 +/- 0.87, respectively. The ability of NS-398 to induce apoptosis is greater than that of indomethacin. Both indomethacin and NS-398 reduced the cell proliferation in a concentration-dependent manner. The IC50 values of NS-398 (54.8 +/- 3.6 and 77.2 +/- 4.9 microM) were significantly lower than those of indomethacin (206.3 +/- 43.0 and 180.3 +/- 22.6 microM) at P < 0.01 in Colo320 and THRC cell lines, respectively. These findings suggest that NS-398, a selective inhibitor of COX-2, is a possible candidate for a chemopreventive agent with a potent apoptosis-inducing effect and low ulcerogenic activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate.

In our studies to find natural compounds with chemopreventive efficacy in foods, using azoxymethane (AOM)-induced colonic aberrant crypt foci and colonic mucosal cell proliferation as biomarkers, a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), present in the edible plant Languas galanga from Thailand was found to be effective. This study was conducted to test the ability of ACA to inhibit AOM-induced colon tumorigenesis when it was fed to rats during the initiation or post-initiation phase. Male F344 rats were given three weekly s.c. injections of AOM (15 mg/kg body weight) to induce colonic neoplasms. They were fed diet containing 100 or 500 ppm ACA for 4 weeks, starting one week before the first dosing of AOM (the initiation feeding). The other groups were fed the ACA diet for 34 weeks, starting one week after the last AOM injection (the post-initiation feeding). At the termination of the study (week 38), AOM had induced 71% incidence of colonic adenocarcinoma (12/17 rats). The initiation feeding with ACA caused significant reduction in the incidence of colon carcinoma (54% inhibition by 100 ppm ACA feeding and 77% inhibition by 500 ppm ACA feeding, P = 0.03 and P = 0.001, respectively). The post-initiation feeding with ACA also suppressed the incidence of colonic carcinoma (45% inhibition by 100 ppm ACA feeding and 93% inhibition by 500 ppm ACA feeding, P = 0.06 and P = 0.00003, respectively). Such inhibition was dose-dependent and was associated with suppression of proliferation biomarkers, such as ornithine decarboxylase activity in the colonic mucosa, and blood and colonic mucosal polyamine contents. ACA also elevated the activities of phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. These results indicate that ACA could inhibit the development of AOM-induced colon tumorigenesis through its suppression of cell proliferation in the colonic mucosa and its induction of GST and QR. The results confirm our previous finding that ACA feeding effectively suppressed the development of colonic aberrant crypt foci. These findings suggest possible chemopreventive ability of ACA against colon tumorigenesis.

Animal Feed↗
PubMed1997

Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart.

The effect of MET-88 (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), a gamma-butyrobetaine (gamma-BB) hydroxylase inhibitor, on the hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in the isolated rat heart, which was perfused aerobically by the Langendorff's technique at a constant flow rate and driven electrically. In the first series of experiments, MET-88 (100 mg/kg/d) was orally administered to rats for 10 days prior to isolation of the heart. In the second series of experiments, MET-88 or gamma-BB was directly infused to the isolated perfused heart. In both series of experiments, H2O2 (600 microM) decreased the left ventricular developed pressure (mechanical dysfunction) and the tissue levels of high-energy phosphates (metabolic derangement). In the first series of experiments, oral pretreatment with MET-88 attenuated the H2O2-induced metabolic derangement with a marked increase in the myocardial level of gamma-BB, while it did not attenuate the H2O2-induced mechanical dysfunction. In the second series of experiments, MET-88 (1 mM) did not attenuate the H2O2-induced metabolic derangement, whereas gamma-BB (500 microM or 1 mM) attenuated it. Nevertheless, gamma-BB did not modify the energy metabolism of H2O2-untreated heart (normal heart). These results suggest that oral pretreatment with MET-88 protects the energy metabolism against the H2O2-induced derangement and that the beneficial effect of the oral pretreatment with MET-88 may be mediated by gamma-BB that has accumulated in the myocardium because of inhibition of gamma-BB hydroxylase.

Adenosine Diphosphate↗
PubMed1997

Protective effects of dilazep and its derivative K-7259 on the haemolysis induced by amphiphiles in rat erythrocytes.

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-L-carnitine (PAL-CAR) or palmitoyl 1-alpha-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 microM, respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 microM) but not at the highest concentration used (1 mM). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 microM to 1 mM. Similarly, dilazep (1 to 100 microM) and K-7259 (1 microM to 1 mM) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 microM, did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

Animals↗
PubMed1997

Lidocaine attenuates mechanical and metabolic derangements induced by palmitoyl-L-carnitine in the isolated perfused rat heart.

The effect of lidocaine on the palmitoyl-L-carnitine (PALCAR)-induced mechanical and metabolic derangements was studied in Langendorff rat hearts, perfused aerobically at a constant flow rate and paced electrically. PALCAR (5 mumol/l) increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., mechanical dysfunction), and decreased the tissue levels of adenosine triphosphate and creatine phosphate (i.e., metabolic change). These mechanical and metabolic alterations induced by PALCAR were concentration-dependently attenuated by lidocaine (20, 50 or 100 mumol/l). Nevertheless, lidocaine (20, 50 or 100 mumol/l) did not affect the mechanical function and energy metabolism of the normal (PALCAR-untreated) heart. These results indicate that lidocaine has a cardioprotective action against the PALCAR-induced mechanical and metabolic derangements.

Adenosine Triphosphate↗
PubMed1997

[A sensitive fluorometric assay for dihydrodiol dehydrogenase].

Dihydrodiol dehydrogenase (DD) oxidizes naphthalene dihydrodiol to 1,2-dihydroxynaphthalene, which is immediately autoxidized to 1,2-naphthoquinone. Here we established a fluorometric assay for the enzyme, which is based on the conversion of 1,2-naphthoquinone to fluorescent compounds by reacting with ethylenediamine. The formed fluorescent compounds were synthetically identified as 6-(2-aminoethylamino)benzo[f]quinoxaline and 2,6- or 3,6-bis(2-aminoethylamino)benzo[f]quinoxaline, which showed the same fluorescence at 550 nm at an excitation wavelength of 420 nm. This method provides a 9000-fold increase in sensitivity over a currently available assay which measures the change in the absorbance of a cofactor, NADPH. Since this simple and sensitive method allowed many samples to be assayed simultaneously, we applied it to the analysis of multiple forms of DD, separated by an anion-exchange chromatography, from six human liver specimens.

Ethylenediamines↗
PubMed1997

Cardioprotective effect of K-7259, a novel dilazep derivative, against ischemia-reperfusion damage in isolated, working rat hearts.

Global ischemia (15 min) followed by reperfusion (10, 20 or 30 min) was performed in isolated, working rat hearts. Ischemia depressed mechanical function, which was not restored by reperfusion of 20 min. Preischemic administration of K-7259 (N,N'-bis[4-(3,4,5-trimethoxyphenyl)butyl]homopiperazine dihydrochloride) (1, 5 or 10 microM) decreased the function before ischemia, but it attenuated the ischemia-induced dysfunction during reperfusion (20 min). Postischemic administration of K-7259 (10 microM) or dilazep (20 microM) also attenuated the ischemia-induced dysfunction during reperfusion (30 min). Ischemia-reperfusion (10 min) increased the tissue malondialdehyde level, and postischemic administration of K-7259 (10 microM) or dilazep (20 microM) attenuated the malondialdehyde accumulation. K-7259 has a cardioprotective effect when given either before or after ischemia.

Animals↗
PubMed1997

Beneficial effects of dilazep on the palmitoyl-L-carnitine-induced derangements in isolated, perfused rat heart: comparison with tetrodotoxin.

The present study was carried out to determine the effect of dilazep, having an inhibitory effect on the Na+ channel, on the mechanical dysfunction and metabolic derangements induced by palmitoyl-L-carnitine in isolated rat heart and to compare the effect of dilazep with that of tetrodotoxin, a specific inhibitor of the Na+ channel. Rat hearts were perfused aerobically at a constant flow according to Langendorff's technique and paced electrically. Palmitoyl-L-carnitine (5 microM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure (i.e., it produced mechanical dysfunction), decreased the tissue level of adenosine triphosphate and increased the tissue level of adenosine monophosphate (i.e., it produced metabolic derangements). These mechanical and metabolic alterations induced by palmitoyl-L-carnitine were attenuated by either dilazep (1 microM) or tetrodotoxin (3 microM). On the other hand, neither dilazep nor tetrodotoxin modified the mechanical function and energy metabolism of the normal (palmitoyl-L-carnitine-untreated) heart. These results suggest that inhibition of the Na+ channel with dilazep or tetrodotoxin is responsible, at least in part, for attenuating the palmitoyl-L-carnitine-induced mechanical dysfunction and metabolic derangements in the heart.

Adenosine Diphosphate↗
PubMed1997

A new approach to the development of anti-ischemic drugs. Substances that counteract the deleterious effect of lysophosphatidylcholine on the heart.

Lysophosphatidylcholine (LPC) is an amphiphilic metabolite that can be produced from membrane-phospholipids by activation of phospholipase A2 (PLA2), and it accumulates in the heart during ischemia and reperfusion. It is known that LPC is an arrhythmogenic substance. Recent studies have revealed that LPC produces mechanical and metabolic derangements in perfused working rat hearts, and Ca(2+)-overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like effect on the heart. LPC accumulated in the myocardium activates phospholipase A2, establishing a vicious circle; i.e. LPC itself has an ability to produce another LPC. Therefore, a drug that has an anti-LPC effect would protect or improve ischemia/reperfusion damage. This article will review the effect of LPC in relation to ischemia, and consider a possibility of developing new anti-ischemic drugs on the basis of the anti-LPC action.

Adrenergic beta-Antagonists↗
PubMed1997

Microcystic meningioma without enhancement on neuroimaging--case report.

A 63-year-old female presented with an unusual case of microcystic meningioma manifesting as a 4-year history of unsteady gait, dysarthria, and hearing loss. Computed tomography disclosed a large hypodense mass in the right cerebellopontine angle, clivus, and middle fossa, with slight contrast enhancement. T1-weighted magnetic resonance images demonstrated the lesion as a hypointense mass, which was little enhanced gadolinium-diethylenetriaminepenta-acetic acid. Right carotid angiography revealed blood supply from the external carotid artery, but no tumor staining. The extracerebral tumor was subtotally removed. The histological diagnosis was microcystic meningioma. Light microscopy revealed abundant microcystic throughout the tumor tissue, and electron microscopy disclosed that the microcysts were mostly located in the extracellular spaces and only a few in the cytoplasm. Microcystic meningioma without enhancement is rare and should be differentiated from low-grade astrocytoma, epidermoid, or other non-enhanced tumor.

Brain Neoplasms↗
PubMed1997

[Changes in tissue and blood polyamines during N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinogenesis in rats].

BACKGROUND: Polyamine are recognized as cell growth factors. We studied in order to determine whether alterations in the levels of tissue and blood polyamines were useful biochemical markers for bladder tumor. METHODS: The concentrations of three polyamines, diamine, spermidine and spermine, in urinary bladder and blood were determined during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in male F344 rats. At 5 weeks of age, rats were given 0.05% BBN in the drinking water for 20 weeks. RESULTS: BBN induced bladder hyperplasia in 4 of 5 rats at 8 weeks, papillomas in 2 of 5 rats at 12 weeks, and transitional cell carcinoma in all the rats by 20 weeks. The levels of total polyamine in both bladder and blood of the rats during 12-20 weeks were significantly higher than those of the control animals given water alone. The elevation of total polyamine was mainly due to the increase of spermidine of the three polyamines, which was coincident with the incidence of bladder tumors. CONCLUSION: The results indicated that the polyamines are excellent biochemical markers for bladder tumors.

Animals↗
PubMed1997

[Changes in tissue and blood polyamine levels following chemotherapy in rats with urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl) nitosamine in rats].

BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to determine whether alterations in the levels of tissue and blood polyamines were useful biochemical makers for monitoring the efficacy of the chemotherapy for bladder tumors. METHODS: The concentrations of three polyamines of diamine, spermidine and spermine in urinary bladder and blood were determined in male F344 rats with urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), following chemotherapy with cisplatin, methotrexate and pirarubicin. RESULTS: Bladder carcinoma was observed in 5 of 20 rats of the chemotherapeutic group, and 16 of 20 rats of the control group given saline alone. The levels of spermidine, spermine and total polyamine in both bladder and blood of the treated rats were significantly lower than those of the control rats. CONCLUSION: The study suggested that the levels of tissue and blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy for bladder tumors.

Animals↗
PubMed1997

Effect of isosorbide on distortion-product otoacoustic emissions and endocochlear DC potential in experimentally induced hydropic ears.

The effects of isosorbide on distortion-product otoacoustic emissions (DPOAEs) and endocochlear DC potential (EP) were examined in experimentally induced endolymphatic hydropic ears and untreated control ears using 20 albino guinea pigs. DPOAEs and EP in the hydropic ears decreased after obliteration of the endolymphatic duct and sac. The administration of isosorbide restored DPOAEs to the normal level, whereas EP was further reduced. In control ears there was no significant change in DPOAEs and EP after the administration of isosorbide. The results obtained in the present study indicate that the effect of isosorbide on DPOAEs is different from that on EP, and the recovery of DPOAEs in hydropic ears is not a secondary phenomenon due to the recovery of EP.

Acoustic Stimulation↗