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S Tsuruoka

Publications and source records attributed to S Tsuruoka.

At least 37 records · Page 2Linked to original sources
PubMed2000

Serial positron emission tomography (PET) in gliomatosis cerebri treated with radiotherapy: a case report.

Results of serial positron emission tomography (PET) in a biopsy-proven case of gliomatosis cerebri (GC) are reported. Computed tomography (CT) with and without contrast failed to detect focal abnormalities, but magnetic resonance (MR) revealed iso-intensity or low-intensity lesions in T1-weighted images and high-intensity lesions in T2-weighted images. Lesions were seen in the left thalamus, right temporal lobe and claustrum, and pons. Radiotherapy remarkably improved clinical and imaging findings. Both before and shortly after radiotherapy, 11C-methionine PET images showed hypermetabolism while 15O-water PET images showed a marked increase in cerebral blood flow in GC lesions. However, 6 months later PET images had remarkably improved, appearing nearly normal.

Adult↗
PubMed2000

Ranitidine clearance during hemodialysis with high-flux membrane: comparison of polysulfone and cellulose acetate hemodialyzers.

OBJECTIVE: To compare the effect of hemodialysis using two different types of dialyzer membranes, polysulfone (PS), a high-flux membrane, and cuprophane (CP), a conventional membrane, on blood ranitidine concentration. BACKGROUND: Recent advances in hemodialyzer membranes have improved the removal of small and middle size uremic toxins, while little is known about the change of drug removal by new membranes. METHODS: Eight patients with chronic renal failure who received ranitidine (150 mg/day) on a chronic basis were included. During the dialysis, blood samples were obtained from both the arterial and venous sides (before and after, respectively) of the dialyzer. RESULTS: Serum concentration of ranitidine decreased more on PS [54 +/- 3% (+/- SEM) reduction after 3 h] than on CP (35 +/- 4%). The dialyzer clearance of ranitidine on PS membrane (67.2 +/- 4.4 ml/min/m2) was significantly higher than that on CP (43.1 +/- 3.8 ml/min/m2, P < 0.001). Elimination fraction (EF) of the drug during the dialysis with PS was also significantly higher than that with CP (72 +/- 2% versus 44 +/- 3%). Apparent half-life of ranitidine during dialysis with PS (2.9 +/- 0.4 h) was shorter than that with CP (5.1 +/- 0.7 h). However, the amount of ranitidine removed by a single dialysis with PS membrane was less than 20 mg. CONCLUSION: Ranitidine clearance by hemodialysis is significantly higher with PS than with CP. Although additional dose adjustment may not be needed for ranitidine, the type of dialyzer membrane can affect drug elimination and should be taken into account for consideration of drug removal by hemodialysis.

Cellulose↗
PubMed2000

Time-dependent nephrotoxicity associated with daily administration of cisplatin in mice.

The chronopharmacokinetics and chronopharmacodynamics of cisplatin were studied in a mouse model to reveal the mechanisms of dosing time-dependent nephrotoxicity induced by daily administration. Chronotoxicity was tested by daily intraperitoneal injections of cisplatin (6mg kg(-1)) for 5 days at four time points (04:00, 10:00, 16:00 and 22:00h) in BALB/c mice (n = 6 in each group). After following the changes in body weight, serum concentrations of blood urea nitrogen (BUN) and creatinine obtained on day 6 were compared. The results showed diurnal variations in cisplatin toxicity, with the 04:00 and 16:00h time points the best and the worst, respectively. We then measured platinum concentrations in blood, liver and kidney and compared the results of the 04:00 and 16:00 h groups (n = 4 in each group). Kidney sensitivity to cisplatin alone, lipopolysaccharide (LPS) alone, cisplatin with LPS and saline (control) were also measured using a tissue culture system (a measurement system of interleukin-6 (IL-6) production) between the 04:00 and the 16:00 h groups (n = 4 in each group). These results showed no significant difference in platinum accumulation between the two groups. IL-6 production was higher in the 16:00 h group than in the 04:00 h group after saline injection alone (P < 0.05). Cisplatin treatment alone did not increase IL-6 production. However, IL-6 levels were markedly augmented by cisplatin with LPS. In conclusion, chrononephrotoxicity induced by daily cisplatin administration does not only depend on cisplatin accumulation, but might also depend on kidney sensitivity to diurnal variations in inflammatory reaction without direct cisplatin toxicity.

Animals↗
PubMed2000

Acute effect of cadmium-metallothionein on glucose and amino acid transport across the apical membrane of the rabbit proximal tubule perfused in vitro.

Acute as well as chronic exposure of cadmium (Cd) leads to proximal tubule injury. The exact cellular mechanism of this disorder and whether there is a contribution of cadmium-metallothionein (Cd-MT), a binding protein of Cd, remain unclear. We perfused isolated S2 segments of rabbit nephron, and the deflections of transmural voltage (DeltaV(t)) and apical membrane voltage (DeltaV(a)) on elimination of glucose or alanine from the perfusate were measured for the parameters of activity of Na(+)-glucose and Na(+)-amino acid cotransporters. The effects of Cd-MT or CdCl(2) to either bath or lumen for 10 min on these parameters were examined. We also measured the lumen-to-bath [(14)C]glucose flux. Addition of Cd-MT to lumen suppressed glucose- or alanine-dependent DeltaV(t) and DeltaV(a), as well as baseline V(t) and basolateral membrane voltage (V(b)), at approximately 10 min. [(14)C]glucose flux was inhibited by Cd-MT to lumen. The effects of Cd-MT to bath and CdCl(2) to either lumen or bath were 100-fold less potent than that of Cd-MT to lumen. Luminal Cd-MT immediately suppressed the glucose-dependent DeltaV(a), whereas the baseline V(a) and V(t) were unchanged. The early effect of luminal Cd-MT was simulated by addition of 10(-4) M phloretin. Addition of 10(-4) M ouabain to the bath simulated the later effect of Cd-MT. The protection of SH group by dithiothreitol prevented the early effect of Cd-MT, but not the later effect. We concluded that Cd-MT initially acts directly on Na(+)-glucose and Na(+)-amino acid cotransporters from the lumen by attacking SH group, followed by the later inhibition of Na(+)-K(+)-ATPase after entering the cell from the apical membrane.

Alanine↗
PubMed2000

Pure sensory stroke caused by a cerebral hemorrhage: clinical-radiologic correlations in seven patients.

BACKGROUND AND PURPOSE: Pure sensory stroke (PSS) usually is caused by a lacunar infarct; reports of PSS caused by cerebral hemorrhage have been rare. We correlated clinical and neuroradiologic findings in patients with PSS caused by cerebral hemorrhage. METHODS: We retrospectively studied seven patients with appropriate clinical findings and lesions revealed by X-ray CT and MR imaging (five men, two women; age range, 46-64 years; mean age, 55.9 years). RESULTS: Hemorrhages involved the thalamus, pons, internal capsule, or cerebral cortex. MR imaging revealed thalamic PSS was located in the ventral posterior lateral (VPL) or ventral posterior medial (VPM) nucleus; a lesion producing a thalamic cheiro-oral syndrome was situated on the border between the VPL and VPM. Pontine PSS involved the medial lemniscus together with the ventral trigeminothalamic tract, sparing the anterior and lateral spinothalamic tracts. Accordingly, pontine PSS, but not thalamic PSS, selectively affected vibration and position sense while leaving pinprick and temperature perception intact, and oral sensory involvement was bilateral when cheiro-oral syndrome had a pontine origin. MR imaging revealed hemorrhage in the postcentral gyrus in the cortical variety of PSS and in the posterior part of the posterior limb (thalamocortical sensory pathway) in PSS of internal capsular origin. The postcentral gyral lesion impaired stereognosis and graphesthesia. CONCLUSION: Focal hemorrhages can lead to purely sensory stroke syndromes, and the clinical deficits are fairly well linked with the locations of the bleeds.

Brain↗
PubMed1999

Chronotherapy of high-dose 1,25-dihydroxyvitamin D3 in hemodialysis patients with secondary hyperparathyroidism: a single-dose study.

BACKGROUND: A high-dose oral intermittent vitamin D (pulse therapy) is widely used for the treatment of secondary hyperparathyroidism associated with kidney failure. However, hypercalcemia by vitamin D sometimes interrupts this treatment. Because serum calcium concentration possesses a circadian rhythm, a chronopharmacologic approach of vitamin D may have merit for avoidance of adverse reactions. METHODS: Six female secondary hyperparathyroidism patients receiving maintenance hemodialysis received a single oral dose of 2 microg 1,25-dihydroxyvitamin D3 at either 8 AM or 8 PM in a crossover design. Serum concentrations of ionized and total calcium, phosphate, and vitamin D3 were determined for a 48-hour period after administration. We also measured serum intact parathyroid hormone before and 48 hours after dosing as an index for efficacy. RESULTS: A single oral administration of the drug caused an increase in concentration of ionized calcium, serum calcium, and phosphate. However, the area under concentration-time curve from zero to 48 hours [AUC(0-48)] and peak concentration of these variables were markedly lower after dosing at 8 PM. Pre-dose concentrations of these variables were lower at night. The AUC(0-48) of serum vitamin D3 of the morning and night trials did not differ significantly. Reduction of intact parathyroid hormone concentration was also similar between the two trials. CONCLUSION: The administration of vitamin D3 at night may reduce the occurrence of hypercalcemia and hyperphosphatemia in patients with secondary hyperparathyroidism, whereas the pharmacokinetics and intact parathyroid hormone-lowering effect of the drug does not vary with dosing time.

Area Under Curve↗
PubMed1999

Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats.

We have investigated the influence of a novel angiotensin II type 1 receptor antagonist, candesartan cilexetil, on the oxidative state of renal tissue and renal function in 5/6 nephrectomized rats, and compared its effects with those of an angiotensin-converting enzyme inhibitor, enalapril. Candesartan cilexetil (1 and 5 mg/kg per day), enalapril (5 mg/kg per day) and vehicle were orally administered once daily for 16 weeks after 5/6 nephrectomy. There was a marked degree of proteinuria evident prior to treatment, an average of 5.69 mg/mg creatinine in the nephrectomized rats, vs 1 to 2 mg/mg creatinine in the control group matched for species and body weight. Inhibition of development of proteinuria by candesartan cilexetil was dose dependent. Enalapril also significantly blunted the rise in urinary protein. Malondi-aldehyde content in the homogenate from the renal cortex increased significantly in the nephrectomized rats compared to control animals. This elevation of malondi-aldehyde content was unaffected by administration of either candesartan cilexetil or enalapril. Antioxidative enzyme (glutathione peroxidase, superoxide dismutase, and catalase) activities in the renal tissue were not affected by any active treatment. Elevation of lipid peroxide in remnant renal tissue suggests that oxidative stress may contribute to the progression of renal injury in the nephrectomized rats. Neither candesartan cilexetil nor enalapril affected antioxidant defenses in renal tissue in nephrectomized rats, indicating that mechanisms other than alteration in oxidative stress are involved in the renoprotective effects of candesartan cilexetil and enalapril.

Angiotensin Receptor Antagonists↗
PubMed1999

Hyperlipidaemia and the progression of nephropathy in OLETF rats: effect of angiotensin-converting enzyme inhibitor, enalapril.

1. The influence of angiotensin-converting enzyme (ACE) inhibitor is investigated in enalapril on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneously non-insulin-dependent diabetes (NIDDM). 2. Enalapril (5 mg/kg) or vehicle was administered once daily by gastric gavage to 22-week-old male OLETF rats for 32 weeks. Blood pressure, albuminuria, creatinine clearance, plasma glucose, serum insulin and lipids were determined before and during the treatment. Renal haemodynamics was examined at the end of the treatment. 3. Enalapril lowered blood pressure mildly but significantly. In the vehicle-treated rats, urinary albumin excretion increased from 0.75 +/- 0.16 mg/mg creatinine (Cr) to 8.65 +/- 0.78 mg/mg Cr. Enalapril significantly blunted the development of albuminuria from 0.66 +/- 0.12 mg/mg Cr to 5.19 +/- 0.67 mg/mg Cr (P < 0.008) without significant influence on creatinine clearances. Enalapril also significantly blunted the rise in serum cholesterol and triglyceride prior to the development of massive albuminuria. Enalapril did not affect bodyweight, plasma glucose or insulin levels. Renal haemodynamics assessed by inulin and p-aminohippuric acid clearances were similar in both groups at the end of the treatment. 4. These results reconfirmed that the ACE inhibitor has protective effects on nephropathy in NIDDM. Massive albuminuria was preceded by increase in serum lipids in OLETF rats, which supports the view that hyperlipidaemia exacerbates glomerular injury in chronic renal disease. Enalapril attenuated the rise in serum lipids, suggesting that the beneficial effects of the compound on renal injury in OLETF rats might also be mediated through the action of affecting serum lipids.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Removal of digoxin and doxorubicin by multidrug resistance protein-overexpressed cell culture in hollow fiber.

BACKGROUND: Drug removal by hemoperfusion is not effective because of its lower capacity and nonspecificity. We invented a new hybrid type of hemodialysis system. METHODS: An immortalized proximal tubular cell line (PCTL) overexpressing human multidrug resistance protein-1 (MDR-1) was cultured either on polus filter membranes or on hollow fiber modules. The modules were incubated in an incubator conditioned with 95% O2/5% CO2 that was kept at 37 degrees C. At 10 days on culture, the drug-transporting capacity of these systems was examined. RESULTS: MDR was successfully expressed in the PCTL as evaluated by Western blot. Basolateral to apical transport of 3H-digoxin, a substrate of MDR, was examined by using the cells cultured on a microporous membrane. PCTL-MDR showed a 10-fold increase in MDR protein and a 12-fold increase of 3H-digoxin transport through a cell layer on a microporous membrane. The increase of the transport was abolished by the addition of 5 microM verapamil, an inhibitor of MDR, to the apical side. When digoxin or doxorubicin was infused in the capillary side of the hollow fiber modules after 10 days on culture, the largest portion of the drugs was transported to the pericapillary side (P < 0.001). This transport was also abolished by an addition of verapamil to the pericapillary side. Transport of para-aminohippurate was not different between two cells, and inulin was not transported in this system. CONCLUSION: The hybrid hollow fiber system can selectively remove a significant amount of drugs that have an affinity to MDR from the medium, and perfuse them to the capillary side in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Mechanisms of HCO(-)(3) secretion in the rabbit connecting segment.

The connecting tubule (CNT) contains alpha-(H(+)-secreting) and beta-(HCO(-)(3)-secreting) intercalated cells and is therefore likely to contribute to acid-base homeostasis. To characterize the mechanisms of HCO(-)(3) transport in the rabbit CNT, in which there is little definitive data presently available, we microdissected the segments from the superficial cortical labyrinth, perfused them in vitro, measured net HCO(-)(3) transport (J(HCO(-)(3))) by microcalorimetry, and examined the effects of several experimental maneuvers. Mean +/- SE basal J(HCO(-)(3)) was -3.4 +/- 0.1 pmol. min(-1). mm(-1) (net HCO(-)(3) secretion), and transepithelial voltage was -13 +/- 1 mV (n = 47). Net HCO(-)(3) secretion was markedly inhibited by removal of luminal Cl(-) or application of basolateral H(+)-ATPase inhibitors (bafilomycin or concanamycin), maneuvers that inhibit beta-intercalated cell function. Net HCO(-)(3) secretion was not affected by inhibitors of alpha-intercalated cell function (basolateral Cl(-) removal, basolateral DIDS, or luminal H(+)-ATPase inhibitors). Net HCO(-)(3) secretion was stimulated by isoproterenol and inhibited by acetazolamide. These data indicate that 1) CNTs secrete HCO(-)(3) via an apical DIDS-insensitive Cl(-)/HCO(-)(3) exchanger, mediated by a basolateral bafilomycin- and concanamycin-sensitive H(+)-ATPase; 2) inhibition of cytosolic carbonic anhydrase decreases HCO(-)(3) secretion; and 3) stimulation of beta-adrenergic receptors increases HCO(-)(3) secretion. The failure to influence net HCO(-)(3) transport by inhibiting alpha-intercalated cell apical H(+)-ATPases or basolateral Cl(-)/HCO(-)(3) exchange suggests that the CNT has fewer functioning alpha-intercalated cells than the cortical collecting duct. These are the first studies to examine the rate and mechanisms of HCO(-)(3) secretion by the rabbit CNT; this is clearly an important segment in mediating acid-base homeostasis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.

We have recently cloned and characterized a unique sodium bicarbonate cotransporter, NBC3, which unlike other members of the NBC family, is ethylisopropylamiloride (EIPA) inhibitable, DIDS insensitive, and electroneutral (A. Pushkin, N. Abuladze, I. Lee, D. Newman, J. Hwang, and I. Kurtz. J. Biol. Chem. 274: 16569-16575, 1999). In the present study, a specific polyclonal antipeptide COOH-terminal antibody, NBC3-C1, was generated and used to determine the pattern of NBC3 protein expression in rabbit kidney. A major band of approximately 200 kDa was detected on immunoblots of rabbit kidney. Immunocytochemistry of rabbit kidney frozen sections revealed specific staining of the apical membrane of intercalated cells in both the cortical and outer medullary collecting ducts. The pattern of NBC3 protein expression in the collecting duct was nearly identical to the same sections stained with an antibody against the vacuolar H+-ATPase 31-kDa subunit. In addition, the NBC3-C1 antibody coimmunoprecipitated the vacuolar H+-ATPase 31-kDa subunit. Functional studies in outer medullary collecting ducts (inner stripe) showed that type A intercalated cells have an apical Na+-dependent base transporter that is EIPA inhibitable and DIDS insensitive. The data suggest that NBC3 participates in H+/base transport in the collecting duct. The close association of NBC3 and the vacuolar H+-ATPase in type A intercalated cells suggests a potential structural/functional interaction between the two transporters.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Effect of protamine on ion selectivity of superficial and juxtamedullary proximal straight tubules.

Protamine is known to inhibit cation selectivity of the paracellular shunt pathway in several leaky nephron segments. Ion permeability of the superficial (SF) proximal straight tubules (PST) is selective to Cl(-), whereas that of the juxtamedullary (JM) PST is selective to Na(+). Protamine was used to estimate the contribution of the paracellular shunt pathway to ion selectivity in these segments. PSTs were isolated from the kidneys of Japanese white rabbit and microperfused in vitro. The ratio of Na(+) to Cl(-) permeability (P(Na)/P(Cl)) was estimated from the diffusion potential (dV(T)) generated by NaCl gradients. When 300 microg/ml protamine was added to the lumen, P(Na)/P(Cl) was decreased from 0.33 to 0.26 in SF-PST and from 1.80 to 1.29 in JM-PST, respectively, as the results of inhibition of cation selectivity. Addition of 30 U/ml heparin to the lumen, which neutralizes protamine, returned the ratios toward the control levels. Protamine exhibited similar effect on P(Na)/P(Cl) in the presence or the absence of ouabain in the bath, indicating that the observed voltage deflections were independent of the transcellular active transport process. Although P(Na)/P(Cl) was different between SF- and JM-PST, protamine inhibits Na(+) permeability in both segments. Preferential Cl(-) permeability in the SF-PST may be intrinsic to the paracellular route of this segment. The mechanism of this anion selectivity remains to be established.

Algorithms↗
PubMed1999

Levothyroxine-induced liver dysfunction in a primary hypothyroid patient.

Here we report a case of levothyroxine-induced liver dysfunction. T4 (levothyroxine) has been more commonly used for the treatment of hypothyroidism than T3 active hormone (triiodothyronine), because with the former drug a stabler plasma concentration is obtained after oral administration. Although there are few reports on levothyroxine-induced liver dysfunction, we treated a primary hypothyroid patient with high serum aminotransferase after administration of levothyroxine. Liver dysfunction was improved after cessation of the drug administration. Antibody to T4 was found in the serum of the patient after this event. From clinical course and laboratory data of the patient, the episode of liver damage was considered to be induced by levothyroxine. We then administrated triiodothyronine, and it did not induce liver dysfunction. Changing levothyroxine to triiodothyronine resulted in a successful clinical course in this case, as re-administration of the doubtful drug is strictly limited.

Adolescent↗
PubMed1998

Drug-induced Cushing syndrome in a patient with ulcerative colitis after betamethasone enema: evaluation of plasma drug concentration.

The authors report the induction of Cushing syndrome by daily betamethasone enema in a patient with ulcerative colitis, and they determine for the first time the pharmacokinetic profile of betamethasone after rectal dosing. The authors found high plasma concentrations of betamethasone, which could have been enough to cause Cushing syndrome. Suppression of the hypothalamus-pituitary-adrenal axis disappeared after the dose schedule was changed from every day to three times a week. These findings suggest that a considerable amount of betamethasone is absorbed after rectal dosing.

Administration, Rectal↗
PubMed1998

Time-dependent cyclosporine A-induced nephrotoxicity in rats.

1. We investigated the toxicity of cyclosporine A (CsA) with reference to the timing of its administration in rats. 2. To elucidate the time-dependent effects of CsA on renal function and survival rate, CsA (75 mg/kg per day) or vehicle was orally administered once daily at four different times (3, 9, 15 and 21 h after lights on; HALO) over a period of 21 days to male Wistar rats (n = 56) kept in rooms with a 12 h light-dark cycle. 3. On the 7th day after treatment, creatinine clearances (Ccr) of groups dosed at 3 and 9 HALO (inactive period) were not reduced in comparison with clearances of time-matched control rats, whereas Ccr significantly decreased in rats dosed at 15 and 21 HALO (active period). Cyclosporine A markedly increased urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in all dosed groups at the 7th day after treatment, except for rats dosed at 3 HALO. In rats dosed at 3 HALO, Ccr decreased progressively; however, it did not decrease progressively in rats dosed at 9 HALO. In surviving rats treated during the inactive period, urine NAG subsequently returned to control levels. Survival rates were greater in animals dosed during inactive periods than those in groups dosed during active periods. 4. Significant differences in CsA-induced toxicity were obvious as a result of the timing of its administration. A different time course between Ccr and urine NAG excretion was observed during repeated CsA administration. Degenerative changes in proximal tubules were demonstrated after chronic administration of CsA, suggesting that severe and persistent tubular damage cannot be assessed by urinary NAG excretion.

Acetylglucosaminidase↗