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Y Horibe

Publications and source records attributed to Y Horibe.

At least 37 records · Page 2Linked to original sources
PubMed1998

Carrier-mediated transport of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, in the pigmented rabbit conjunctiva.

In this study, the transport mechanism of NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor that may be useful for alleviating intraocular inflammation, was characterized in the pigmented rabbit conjunctiva. L-NA, when applied to the mucosal side of the conjunctiva, led to dose-dependent increases in the short-circuit current (Isc) at 37 degrees C but not at 4 degrees C or under the Na+-free condition. Serosally added 1 mM L-NA did not elicit any change in the Isc. Mucosally added 1 mM L-NA elicited a net absorptive Na+ flux of 0.09 microEq/(cm2.hr), comparable with the Isc change. L-NA transport at 0.1 mM in the mucosal-to-serosal (ms) direction was 22 times greater than that in the serosal-to-mucosal direction. There was a good correlation between the ms flux of L-NA and the Isc changes elicited by L-NA under the same experimental conditions. L-NA transport was saturable, with a Km of 0.35 mM and a maximal flux of 290 pmol/(cm2.min). Hill analysis of L-NA flux observed at 0.1 mM L-NA in response to varying Na+ concentrations in the mucosal bathing fluid yielded a Hill coefficient of 0.98, suggesting a 1:1 coupling between Na+ and L-NA. Moreover, ms 3H-L-NA transport was inhibited by basic amino acids (L-Arg and L-Lys) and a neutral amino acid (L-Leu), but not by an acidic amino acid (L-Glu) and the D-stereoisomer of L-NA. In the case of L-Arg, inhibition was competitive with a Ki of 0.034 mM. Taken together, the above findings are consistent with the involvement of the L-Arg transport system B0,+ in the conjunctival transport of L-NA.

Animals↗
PubMed1998

Carrier-mediated transport of monocarboxylate drugs in the pigmented rabbit conjunctiva.

PURPOSE: To determine whether an Na+-dependent monocarboxylate transport process exists on the mucosal side of the pigmented rabbit conjunctiva and to evaluate how it may contribute to the absorption of ophthalmic monocarboxylate drugs. METHODS: L-lactate was used as a model substrate. The excised pigmented rabbit conjunctiva was mounted in a modified Ussing chamber for the measurement of short-circuit current (Isc) and 14C-L.-lactate transport. RESULTS: When added to the mucosal side at 37 degrees C and at pH 7.4, applications of as much as 40 mM L- and D-lactate increased Isc in a saturable manner. By contrast, no change in Isc was observed at 4 degrees C or under the mucosal Na+-free condition. 14C-L-lactate transport in the mucosal-to-serosal (m-s) direction at 0.01 mM revealed directionality, temperature dependency, Na+ dependency, and ouabain sensitivity, but not pH dependency. L-lactate transport in the m-s direction consisted of a saturable Na+-dependent process by the transcellular pathway and a nonsaturable process by the paracellular pathway. For the saturable process, the apparent Michaelis-Menten constant was 1.9 mM, the maximum flux was 8.9 nanomoles/cm2 per hour, and the apparent Na+ :L-lactate coupling ratio was 2:1. 14C-L-lactate transport in the m-s direction was significantly inhibited (46% to 83%) by the mucosal presence of various monocarboxylate compounds, but not by dicarboxylate compounds, zwitterionic compound, D-glucose, amino acids, and peptidomimetic antibiotics. Monocarboxylate nonsteroidal anti-inflammatory drugs and the antibacterial fluoroquinolones inhibited 14C-L-lactate transport by 40% to 85%, whereas prostaglandins and cromolyn had no effect. CONCLUSIONS: An Na+-dependent monocarboxylate transport process that may be used by non-steroidal anti-inflammatory and fluoroquinolone antibacterial drugs for transport appears to be present on the mucosal side of the pigmented rabbit conjunctiva. A possible physiologic role for the Na+-dependent monocarboxylate transport process may be to salvage tear lactate.

Animals↗
PubMed1997

Na(+)-dependent L-arginine transport in the pigmented rabbit conjunctiva.

The objective of this study was to characterize Na(+)-coupled L-arginine (L-Arg) transport in the pigmented rabbit conjunctiva. The excised pigmented rabbit conjunctiva was mounted in the modified Ussing chamber for measurement of short-circuit current (Isc), 3H-L-arginine (3H-L-Arg) flux, and 22Na flux. L-Arg when added to the mucosal side led to 0.32-2.65 microA cm-2 increases in the Isc at 37 degrees C, but not at 4 degrees C or in a Na(+)-free solution. L-Arg at 1 mM stimulated net Na+ absorption by 0.12 microEq cm-2 h-1. The evidence for carrier-mediated transport of L-Arg includes: (1) temperature dependence and saturability over 0.01-10 mM, (2) Na+ dependence and ouabain sensitivity, (3) 84 +/- 2% reduction in the apparent permeability coefficient (Papp) of 3H-L-Arg in the presence of excess unlabeled L-Arg (1 mM), and (4) 16-fold difference in L-Arg transport (at 0.1 mM) between the mucosal-to-serosal and the serosal-to-mucosal direction. Moreover, L-Arg transport was inhibited by basic amino acids, large neutral amino acids, and nitric oxide synthase inhibitors, but not by acidic and small neutral amino acids. Kinetic analysis revealed the possible existence of both high and low affinity processes for L-Arg transport. A half maximal concentration (Km) and maximal L-Arg flux (Jmax) values of the low and high affinity processes were 5.90 and 0.07 mM, and 1,248 and 111 pmol cm-2 min-1, respectively. Hill analysis of L-Arg transport at 0.1 mM in the presence of varying Na+ concentrations in the mucosal bathing fluid yielded a Hill coefficient of 0.93, suggesting a 1:1 coupling between Na+ and L-Arg. In conclusion, Na(+)-coupled transport process(es) for L-Arg in accordance with a 1:1 stoichiometry appear to be present on the mucosal side of the pigmented rabbit conjunctiva. The pattern of inhibition by basic and large neutral amino acids and Na+ dependency are suggestive of system B0,(+)-mediated L-Arg transport.

Amino Acids↗
PubMed1997

Polar solute transport across the pigmented rabbit conjunctiva: size dependence and the influence of 8-bromo cyclic adenosine monophosphate.

PURPOSE: To characterize the conjunctival permeability to polar solutes ranging from 182 to 167,000 daltons in molecular weight (m.w.). METHODS: Solute transport across the excised pigmented rabbit conjunctiva with a baseline transepithelial electrical resistance (TEER) of 1,285 +/- 46 ohm.cm2 was evaluated in the modified Ussing chamber under open-circuit conditions. The model solutes were mannitol (m.w. 182), 6-carboxyfluorescein (m.w. 376), and fluorescein isothiocyanate-labeled dextrans (FD4, m.w. 4,400-FD150, m.w. 167,000). RESULTS: For a given solute, the apparent permeability coefficient (Papp) was independent of solute concentration and direction of transport. As expected, the Papp decreased with solute size, from 27.7 x 10(-8) cm/sec for mannitol to 0.31 x 10(-8) cm/sec for FD150. When the experimental temperature was lowered from 37 degrees C to 4 degrees C. Papp decreased by approximately 50% for FD4 through FD40 and by > 80% for both FD70 and FD150. Equivalent pore analysis, assuming restricted solute diffusion via cylindrical, water-filled pores across the isolated tissue, revealed a radius of 5.5 nm at a pore density of 1.9 x 10(8) pores per cm2. The addition of 1 mM 8-bromo cyclic adenosine monophosphate (8-BrcAMP), known to stimulate Cl- secretion and decrease TEER, to the mucosal side of the conjunctiva increased the transport of mannitol, FD4, and FD40 by 28%, while not affecting FD150 transport. CONCLUSIONS: Our findings suggest that polar solutes up to FD40 traverse the conjunctival epithelial barrier primarily by restricted diffusion through equivalent pores of 5.5 nm radius and that solute movement is affected by reduction of TEER. On the other hand, polar solutes of the FD70 or larger may cross the barrier primarily via non-diffusional pathways such as non-specific endocytosis.

Animals↗
PubMed1997

Kinetic evidence for Na(+)-glucose co-transport in the pigmented rabbit conjunctiva.

PURPOSE: To obtain kinetic evidence for the existence of a Na(+)-coupled glucose co-transport process on the mucosal (tear) side of the pigmented rabbit conjunctiva. METHODS: The excised pigmented rabbit conjunctiva was mounted in the modified Ussing chamber for measurement of 22Na and 3H-3-O-methyl-D-glucose (3-O-MG) fluxes. RESULTS: In the presence of 5 mM glucose, the conjunctival tissue showed net Na+ absorption in the mucosal-to-serosal direction at an approximate rate of 0.15 microEq/cm2/h. This net Na+ absorption was abolished by serosally added 0.5 mM ouabain, but not affected by mucosally added 0.1 mM or 1 mM amiloride. There was a 40-60% reduction in net Na+ absorption under the glucose-free condition or in the mucosal presence of 0.5 mM phlorizin. Moreover, serosally added ouabain and mucosally added phlorizin (both at 0.5 mM) significantly decreased the 3-O-MG permeability coefficient in the mucosal-to-serosal direction by about 70%, whereas mucosally instilled 0.1-1.0 mM amiloride was without any effect. Three-O-MG absorption in the mucosal-to-serosal direction appeared to be coupled with Na+ transport with a 1:1 stoichiometry. In addition, this process exhibited temperature dependency, saturability, and directionality. CONCLUSION: Our findings are consistent with Na(+)-glucose cotransport as being one of the mechanisms for mucosal Na+ entry into the epithelial cells of the pigmented rabbit conjunctiva.

3-O-Methylglucose↗
PubMed1997

Effect of collagen cross-linking in collagen corneal shields on ocular drug delivery.

It is well known that some ocular diseases can be treated more effectively with a collagen shield containing drug. The influence of collagen cross-linking on drug delivery is not known. We determined if collagen cross-linking affects ofloxacin bioavailability at three different collagen shield dissolution times. In this study, the collagen shields were not impregnated in drug but an eye drop was simply instilled after application of collagen shield. A non-cross-linked collagen shield, with a dissolution time of 12 h, disappeared more rapidly from the rabbits' eyes due to proteolysis after application in vivo. On the other hand, the cross-linked collagen shields, with dissolution times of 24 and 72 h, served as an ofloxacin depot and enhanced topical ofloxacin penetration into the cornea and the aqueous humor. As the dissolution times for the cross-linked collagen shield are longer than those of the non-cross-linked type, they serve as drug reservoirs. Therefore, cross-linked collagen shields might be useful ocular drug delivery devices because they can allow drug concentrations to achieve higher levels in the cornea and aqueous humor.

Absorption↗
PubMed1993

A patient with early gallbladder cancer derived from a Rokitanski-Aschoff sinus.

We present herein a case of a 40-year-old male with early gallbladder cancer derived from a Rokitanski-Aschoff sinus (RAS). The patient originally presented at our hospital with epigastric discomfort, following which a diagnosis of adenomyomatosis (ADM) of the gallbladder was made, and a cholecystectomy performed. Histopathological examination of the resected specimen revealed a 7-mm well-differentiated papillo-tubular adenocarcinoma in the RAS epithelium in the body of the gallbladder. The RAS extended to the "pm" layer but the adenocarcinoma was an in situ lesion localized within the RAS epithelium. Considering the difficulties in making an early diagnosis of gallbladder cancer, active surgery should be performed for patients in whom ADM is seen in the gallbladder.

Adenocarcinoma, Papillary↗
PubMed1993

[Transcatheter arterial chemoembolization to hepatic metastases from colorectal cancer].

Response of transcatheter arterial chemoembolization (TAE) and transcatheter arterial infusion chemotherapy to hepatic metastases was reported in 25 cases of colorectal cancer. The severity of liver metastases was H1 in 12 cases, H2 in 9 cases, and H3 in 4 cases. Liver metastases were found during surgery in 12 of these patients, and 13 showed metastases or recurrence in the liver after resections of primary lesions. Catheters were inserted selectively to the proper hepatic artery by Seldinger's method, followed by injection of embolizing agents (gelfoam particles of Lipiodol) with adriamycin or 5-FU + leucovorin in most cases. Response was assessed by blood CEA levels, diagnostic imaging, and period of survival. In 5 cases in whom liver resections were performed following TAE, response was assessed by histopathological findings of the resected specimens. Two patients showed partial response (PR), 12 no change (NC) and 11 progressive disease (PD) by diagnostic imaging. Blood CEA levels fell to less than 50% of pre-treatment levels in 26% of cases. Histological changes by TAE were confirmed in 4 of 5 cases after liver resections, but viable cancer cells were observed in all cases. A case of mucinous cancer showed no change histologically. As the other case of mucinous cancer showed PD by diagnostic imaging, TAE was not suggested to be suitable to treat cases of mucinous cancer. More improvements in the dosage, drugs and times of treatment were suggested to yield a better response rate in TAE therapy for liver metastases from colorectal cancer.

Adult↗
PubMed1990

Inhibitory effect of valproic acid on metabolic clearance of carbamazepine epoxide.

In order to clarify the inhibitory effect of valproic acid (VPA) on the metabolic clearance of carbamazepine-10,11-epoxide (EPO), an active metabolite of carbamazepine, in rat, the disposition of EPO from plasma and the in vitro hydration of EPO were measured in the presence of VPA, in addition to estimating the effect of the antiepileptic on uridine 5'-diphosphoglucuronyltransferase (UDPGT) activity. It was found that the elimination of EPO from plasma was hardly affected by the pretreatment of VPA (100 mg/kg/d for 7 d). However, the elimination was significantly delayed by VPA at steady-state concentration, maintained by the repeated oral administration of the drug, with a 38% decrease in total clearance and a 52% increase in the fraction of EPO eliminated unchanged in urine. The in vitro hydration of EPO was inhibited competitively by VPA at the concentrations comparable to the in vivo levels. The UDPGT activity of hepatic microsomes was also partly inhibited by VPA. These results suggest that VPA at steady state interferes with the metabolic clearance of EPO, by inhibiting the hydration of EPO and glucuronidation of carbamazepine-trans-diol, a hydrated metabolite.

Animals↗
PubMed1989

Effects of anticonvulsants on plasma levels and entero-hepatic circulation of valproic acid and on hepatic drug metabolizing enzyme activities in rats.

To clarify the interaction between valproic acid (VPA) and anticonvulsive drugs such as phenytoin (DPH), phenobarbital (PB) and carbamazepine (CBZ), the effects of these anticonvulsants on the plasma levels and enterohepatic circulation of VPA and on drug metabolizing enzyme activities in liver in relation to their inductive effects were investigated in rats. After intravenous (i.v.) or oral administration, plasma VPA rapidly decreased, and this was followed by a secondary increase in plasma level of VPA due to enterohepatic circulation. When the drug was repeatedly coadministered with DPH or CBZ, the initial VPA elimination from plasma up to 1 h after dosing was less than with VPA alone, while PB significantly enhanced the disappearance of VPA. Judging from the decrease in the area under plasma VPA concentration-time curve from 2 to 9 h (AUC2-9), the enterohepatic circulation of VPA was also decreased by PB, but not by DPH and CBZ. The in vitro and in vivo protein binding of VPA was almost unchanged in the presence of DPH. Cytochrome P-450 content and glucuronyltransferase activity were enhanced following repeated coadministration with PB, DPH or CBZ. These enzyme activities in the animals treated with VPA alone at various dosage levels, however, remained unchanged, indicating that VPA did not inhibit the hepatic drug metabolizing enzyme activities in rats.

Animals↗
PubMed1985

[A case of malignant paraganglioma within the renal sinus].

A case of malignant paraganglioma within the renal sinus is presented. A 51-year-old woman underwent left transabdominal nephrectomy for renal tumor. Pathologically, the tumor was malignant nonchromaffin paraganglioma. This tumor seemed to originate from parasympathetic paraganglions around the left renal artery. Paraganglioma is rare in the literature. Especially, this may be the first report of such a lesion in the renal sinus.

Female↗
PubMed1984

Adult-type systemic varicella in a female patient in course of treatment of her so-called reactive lymphocytic (T-cell) hyperplasia.

A 31-year-old woman was examined in this case. Biopsy revealed an abnormal nontumorous proliferation of T-cells in the lymph node. Clinically, the patient was treated by C-MOPP and steroid under clinical suspicion of T-cell lymphoma. In the period of observation of the course of illness, the patient contracted varicella from her real child and died on the 8th day of illness. She was examined pathologically, electron microscopically, and by the fluorescent antibody technique. Virus infections foci, which were mostly necrotic ones, were found in the parenchymatous and interstitial cells of skin, lung, adrenal gland, digestive organs, liver, lymph nodes, and genital organs. In the circulatory system, proliferative foci with degeneration of endothelial and adventitial cells were noticed in small veins or venules, but little change was found in the arterial system. Electron microscopic observation suggested a destruction of the so-called limiting basement membrane around blood vessels. This was an important finding indicative of a mechanism of viral transmission to the interstitial cell system.

Adult↗