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H Itoga

Publications and source records attributed to H Itoga.

17 recordsLinked to original sources
PubMed2005

Prediction of oral clearance from in vitro metabolic data using recombinant CYPs: comparison among well-stirred, parallel-tube, distributed and dispersion models.

Intrinsic clearances (CLint-HLM-total) for the metabolism of NE-100, metoprolol, clarithromycin (CAM), lornoxicam and tenoxicam were predicted from in vitro data with recombinant cytochorme P450s (CYPs) using relative activity factor (RAF) and then compared with CLint-HLM observed in human liver microsomes (HLM). The predicted CLint-HLM-total correlated well with the observed CLint-HLM in HLM. When oral clearances (CLoral) of low-clearance drugs such as metoprolol, CAM, lornoxicam and tenoxicam were predicted from the in vitro data using four physiological models (well-stirred, parallel tube, distributed and dispersion models), the predicted CLoral corresponded well with the observed CLoralin vivo and were similar among the four models. For a high-clearance drug, the predicted CLoral of NE-100 in extensive CYP2D6 metabolizers (EMs) was substantially different between individual models, although the predicted CLoral in a poor metabolizer of CYP2D6 (PMs) was similar. The CLoral ratio of NE-100 between the EMs and the PMs predicted from the dispersion model, which leads to a reliable prediction for the high-clearance drug, was 48.4, but the ratio decreased depending on the increase of the NE-100 plasma concentration. The results suggest that the CLoral decrease in the EMs is caused by saturation of NE-100 metabolism mediated by CYP2D6 and is based on increases in plasma NE-100 concentrations dependent on the dose of NE-100. The study suggests that the RAF and the in vitro-in vivo scaling approaches are useful for predicting CLoral from in vitro data with recombinant CYPs without using HLM and hepatocytes.

Administration, Oral↗
PubMed2001

Effects of major histocompatibility complex matching on graft survival in allogeneic rat limb transplantation.

Differences in the major histocompatibility complex (MHC) between recipients and donors present a problem because of immunologic responses in graft rejection. The purpose of this study is to clarify the efficacy of MHC matching against acute graft rejection of allogeneic limb transplants in rats. Right hindlimb transplantations were performed using various MHC-mismatched pairs of inbred rats. The rats were classified into 5 groups according to the differences in subregions of the RT1 (rat MHC) between the recipient and the donor: group 1, RT1-A,B,D barrier (the differences of RT1-A,B,D subregions); group 2, RT1-A barrier; group 3, RT1-B,D barrier; group 4, RT1-B barrier; and group 5, RT1-D barrier. The mean survival time significantly decreased in group 1 and increased in group 4. The results suggest that MHC matching clearly improves survival of transplanted limbs. Specifically, both RT1-A and D matching is the most effective compatibility in prolonging survival time of allogeneic limb transplants in rats.

Animals↗
PubMed1992

Involvement of calmodulin- and protein kinase C-related mechanism in an induction process of peroxisomal fatty acid oxidation-related enzymes by hypolipidemic peroxisome proliferators.

Trifluoperazine, a calmodulin antagonist, suppressed the clofibric acid-evoked induction of the peroxisomal cyanide-insensitive fatty acyl-CoA oxidizing system and carnitine acetyltransferase in rat liver and also in cultured rat hepatocytes. H-7, a potent inhibitor of protein kinase C, also suppressed the induction of these enzymes by clofibric acid, bezafibrate, Wyl4,643 or mono(2-ethylhexyl)phthalate in cultured rat hepatocytes. This suppressive effect was also confirmed by the protein composition of hepatocytes treated with clofibric acid and these antagonists, where the increase in the amount of peroxisomal bifunctional enzyme by peroxisome proliferator was markedly suppressed by above two antagonists. Profile of the time-dependent changes in the activities of the two enzymes after clofibric acid treatment showed that there might be two phases in the induction process. The initial phase (0-3 days after the treatment) showed a relative low inducing rate and subsequent phase (3-5 days after the treatment) showed an abrupt induction. The suppressive effect of the above two antagonists was significant in the later phase. In a time course study of the induction process of peroxisomal catalase, bifunctional enzyme or 69 kDa integral membrane protein using immunochemical detection, the induction of the membrane protein by clofibric acid was delayed compared with that of the bifunctional enzyme, where the induction was inhibited almost completely by nicardipine. These experimental results suggest that calmodulin- and protein kinase C-dependent processes play an important role in the process of marked induction of peroxisomal enzymes and membrane protein by drugs in rat liver.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Treatment of infected segmental defect of long bone with vascularized bone transfer.

Experience with infected pseudarthrosis with segmental osseous defect, treated by debridement and microvascular bone transfer, is reported. Fourteen patients form the basis for the study, including 12 males and two females. Patient age at the time of operation averaged 35.1 years. Follow-up averaged 52 months. The affected site included tibia (10), femur (2), and ulna (2). A total of 15 vascularized bone graft transfers were carried out for the 14 patients, with the donor bone fibula (8) and ilium (7). Bony union was ultimately obtained in all patients. In 11 patients, primary union was obtained at both ends of the transferred bone segment. In the remaining three patients, a secondary procedure, consisting of onlay nonvascularized bone autografting at one end of the vascularized transferred bone segment, was required to obtain union. Recurrent infection following union occurred in one patient. One of the two patients with active osteomyelitis at the time of vascularized bone transfer had complications from recurrent sepsis, leading to the authors' caveat that vascularized bone transfer should be deferred until such time as sepsis is inactive. Criteria used in this series for determining inactive sepsis (absence of sinus tracts, negative bacterial cultures, negative c-reactive protein, and a sedimentation rate of less than 15 mm per hour) seem appropriate. The study suggests that vascularized bone transfer is a useful procedure for the treatment of infected segmental osseous defects of long bones, of more than 3 cm extent and one month or more after inactive sepsis.

Adult↗
PubMed1992

Kienbock's disease in an eleven-year-old girl. A case report.

Kienbock's disease occurs most frequently between 20 and 30 years of age (Gillespie, 1961). The youngest patient with Kienbock's disease in literature written in English is a 10-year-old boy (Nakamura et al., 1990). We report the case of an 11-year-old girl with Kienbock's disease whom we treated with radial shortening. Five months after surgery, radiographs showed signs of rapid disappearance of avascular necrosis of the lunate, and the patient had excellent clinical results. Two years postoperatively no recurrence of avascular necrosis of the lunate has occurred.

Age Factors↗
PubMed1991

Hemiresection-interposition arthroplasty of the distal radioulnar joint associated with repair of triangular fibrocartilage complex lesions.

Sixteen wrists of 15 patients with traumatic triangular fibrocartilage complex tears were treated by hemiresection-interposition arthroplasty of the distal radioulnar joint combined with repair of the torn triangular fibrocartilage complex. The surgical procedure was performed to avoid impingement of the ulnar head against the reconstructed triangular fibrocartilage complex. Most of the wrists showed a positive ulnar variance. The average age of the patients was 39 years. Follow-up averaged 41 months. Complete relief of pain was obtained in 10 wrists. Slight pain persisted in 6 wrists, although it was less than before surgery. The range of motion of the wrist joint and forearm improved postoperatively. Grip strength in all wrists increased. Postoperative complications occurred in 7 wrists of 6 patients: reoperation in 2 wrists, fracture in 1, and tendinitis of the extensor carpi ulnaris in 4. All 15 patients subsequently returned to their previous occupations.

Adult↗
PubMed1991

Co-suppression by nicardipine, a calcium antagonist, of induction of microsomal lauric acid hydroxylation with peroxisome proliferation in clofibrate-treated rat liver.

The in vivo effect of nicardipine, a well-known calcium antagonist, on microsomal omega-oxidation of laurate in clofibrate-treated rat liver was studied. The 15.3-fold induction of the activity by 2 weeks administration of 0.25% clofibrate in the diet was markedly suppressed to about 6-fold by co-administration of nicardipine at 100 mg/kg body weight. Similarly, the induction of peroxisomal beta-oxidation and carnitine acetyltransferase activities were also suppressed by this simultaneous administration by more than 50%. Although clofibrate also induced the activity of reduced nicotineamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and increased the hepatic content of cytochrome P-450, no suppressive effect of nicardipine was observed. Contrarily, nicardipine induced the reductase activity and increased the hepatic content of cytochromes P-450 and b5. These results provide the first demonstration of a calcium antagonist, e.g. nicardipine acting as inhibitor of the induction of microsomal omega-oxidation, in association with the inhibition of peroxisome proliferation in animals. The suppression of drug-induced peroxisome proliferation and microsomal omega-oxidation by the calcium antagonist may help in elucidating the causal relationship of the induction mechanisms between peroxisomal and microsomal enzymes.

Animals↗
PubMed1990

Characteristics of the suppressive effect of nicardipine on peroxisome induction in rat liver.

In vivo administration of nicardipine, a known calcium antagonist, suppressed the clofibrate-evoked induction of activities of peroxisomal enzymes, such as catalase, the peroxisomal fatty acyl-CoA oxidizing system, carnitine acetyltransferase and mitochondrial carnitine palmitoyltransferase in rat liver. On a time-course study, the suppression of induction in the activities of the peroxisomal fatty acyl-CoA oxidizing system and carnitine acetyltransferase was found at 5 days after the treatment, whereas the induction by clofibrate was already observed at 1 day after the treatment, suggesting that in the process of peroxisome induction by clofibrate there might be two steps, i.e., a triggering step and an enhancing step, and nicardipine might act as suppressor for the later step. The precursor-incorporation studies with [3H]leucine showed that the rate of the synthesis of the peroxisomal bifunctional enzyme was increased by 4.2-fold after clofibrate-treatment, whereas nicardipine suppressed this enhancement to only 2.2-fold of the control. The rate of degradation of this enzyme was not affected by any treatment. These results show that nicardipine affects the regulation mechanism of the biosynthesis of this enzyme. Nicardipine showed hardly any suppressive-effect on the hepatic peroxisomal enzyme induction observed in high-fat diet fed rat. Furthermore, the suppression of clofibrate-evoked induction of peroxisomal enzymes was observed also in mice. These interesting findings suggest that there is a difference in the mechanism of peroxisome proliferation and/or the induction of peroxisomal enzymes between clofibrate and physiological conditions, such as high-fat diet feeding. The suppression of drug-induced peroxisome proliferation by calcium antagonists may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1990

Reverse-flow vascularized fibular graft: a new method.

The reverse-flow island flap is a relatively recent concept. We have applied this concept to the vascularized bone graft. We report a new method of the reverse-flow vascularized fibular graft for two patients with a pseudarthrosis and massive bone defect of the tibia. The peroneal artery and venae comitantes were severed proximally and elevated with the fibula while maintaining distal vascular continuity. The reverse-flow vascularized fibula was grafted to the posterior aspect of the bone defect of the tibia. Bony union was obtained in both cases. The reverse-flow vascularized fibular graft has many advantages compared with free vascularized fibular graft.

Adult↗
PubMed1990

The latissimus dorsi musculocutaneous flap for extremity reconstruction in orthopedic surgery.

The latissimus dorsi was transferred as a pedicle flap in ten patients and as a free vascular flap in ten others for extremity reconstruction. Group I comprised ten patients in whom the transfer was used solely to cover a skin or soft-tissue defect. Although there was partial necrosis of the transferred skin in one patient, the remaining nine patients obtained complete coverage without further reconstructive surgery. Group II comprised five patients in whom transfer of the latissimus dorsi was performed for active flexion or extension of the elbow or for abduction of the shoulder. Postoperatively, muscle strength obtained was classified from Grades 0 to 5 according to the muscle testing method. Three patients obtained muscle strength of Grade 3, while two obtained Grade 2. Group III comprised five patients who had brachial plexus palsy after high-dose irradiation. Coverage of the skin and soft tissue was performed after neurolysis of the brachial plexus palsy to free the tissue bed of scarred tissue. Postoperatively, sensory and motor disturbances were alleviated in four of five patients.

Adolescent↗
PubMed1989

Vascularized iliac osteocutaneous flap based on the deep circumflex iliac vessels: experience in 13 cases.

We have carried out 13 vascularized iliac osteocutaneous flaps (VIOF) based on the deep circumflex artery (DCIA) and accompanying veins for cases with compound skin and bone defects. Ten of 13 cases obtained bony union at both ends of the iliac crest with only VIOF. Two of the remaining 3 cases obtained bony union at one end only with the VIOF but united at another end with an additional conventional bone grafting procedure. The final case, a traumatic bone defect of the tibia, failed to obtain bony union at either end of the iliac segment. In 5 of 11 patients in which an osteocutaneous flap was used, complete skin flap survival occurred. Of the remaining 6, one flap went on to complete necrosis, and five flaps were complicated by superficial or partial necrosis. The incidence of flap complications was analysed according to the size of flap. Five flaps with complete survival averaged 6.8 x 10.6 cm in size; however, five flaps with superficial or partial necrosis averaged 10.0 x 15.8 cm. These results suggest that the maximal safe skin flap dimension from the DCIA supply alone is probably 10 x 15 cm.

Adolescent↗
PubMed1989

Free vascularized fibular grafts.

Postoperative results in 21 patients with bone defects that had been treated with a free vascularized fibular graft (FVFG) were evaluated. Pathogeneses in 21 patients were bone defect or pseudarthrosis after trauma in eight, massive bone defect after resection of bone and soft tissue tumor in six, congenital pseudarthrosis of the tibia in six, and congenital arteriovenous fistula in the forearm in one patient. The follow-up ranged from 15 months to 12 years, with an average of four years and six months. At final review, 12 patients went on to primary bony union, and six additional patients obtained union following an additional conventional bone graft. Three FVFGs resulted in a non-vascularized fibular graft. However, two patients obtained union with additional bone graft. Only one patient failed to obtain bony union and eventually required an above-knee amputation. Bony union rates in congenital pseudarthrosis of the tibia treated with the FVFG were lower than those in other diseases. Variables related to the surgical procedures and other factors affecting results and complications were also evaluated.

Adolescent↗
PubMed1987

Responses of bradykinin sensitive tooth-pulp driven neurons in cat cerebral cortex.

The properties of single cortical neurons responding to electrical stimulation of the tooth-pulp and to intrapulpal application of bradykinin were studied in the cat. The activities of tooth-pulp driven neurons (TPNs) were recorded from the middle and anterior parts of the coronal gyrus of the cerebral cortex. Bradykinin-sensitive tooth-pulp driven neurons (BK-TPNs) were located in layer IV of area 3b of the anterior part of the coronal gyrus. These neurons had a large cutaneous oro-facial receptive field and received a nociceptive input from the facial skin as well as from the tooth-pulp. The BK-TPNs had a higher threshold and longer latency to electrical stimulation than TPNs insensitive to bradykinin (non BK-TPNs). These findings suggest that BK-TPNs in this cortical area may be involved in sensory processing of noxious information from trigeminal regions.

Action Potentials↗
PubMed1986

Cortical cells driven by the low-threshold tooth pulpal afferent in cats.

The input pattern and spatial distribution of tooth pulp-driven neurons (TPNs) in the cat cortex were studied by recording the unitary activities of these neurons. Stimulation was applied to the upper and lower canine and molar tooth pulps. It was possible to record activities of TPNs in the deep layers of the areas 3a and 3b of the coronal gyrus of cerebral cortex. TPNs driven by the ipsilateral tooth pulp stimulation were distributed more anteroventrally than those driven by contralateral stimulation. Cells driven by bilateral pulp stimulation were situated between these two neurons. The threshold intensity for TPNs in the area 3a was lower than that for neurons in 3b. The majority of TPNs in the area 3a of the anterior part of the coronal gyrus received inputs from low-threshold masseteric muscular afferents as well as from tooth pulp afferents. The findings suggest that TPNs in the area 3a may have a relation to orofacial motor functions.

Animals↗
PubMed1985

Movements of the jaw and orofacial regions evoked by stimulation of two different cortical areas in cats.

Functional properties of the jaw and orofacial motor areas in the cerebral cortex of the lightly anesthetized cat were studied on the basis of the motor effects produced by intracortical microstimulation (ICMS). Jaw and orofacial motor effects were evoked by ICMS (less than 30 microA) delivered to the anterior parts of the coronal and lateral sigmoid gyri (C, coronal area), and the anterior part of the orbital gyrus (O, orbital area). Different patterns of movements in the jaw and orofacial regions were evoked from these two areas. In C one or, at most, two types of simple movement were produced by ICMS to one location, while in O more coordinated movements than those in C were produced. Cytoarchitectonically the jaw and orofacial motor areas were restricted to areas 3a, 4 gamma, and 6a beta in C, and to area 43 in O.

Animals↗
PubMed1985

Distribution and response characteristics of masseteric nerve-driven neurons in two separate cortical projection areas of cats.

Cortical projection areas and distribution and response characteristics of masseteric nerve-driven neurons (MDN) were studied by recording surface-evoked potentials and single neuronal activities elicited by stimulation of the contralateral masseteric nerve in cats. Neuronal activities of MDNs could be recorded in two separate cortical areas. One was located in laminae II-III of area 3b of the posterior part of the coronal gyrus (P), and the other in laminae IV-V of areas 3a and 6a beta of the anterior parts of the coronal and lateral sigmoid gyri (A). The majority of MDNs were driven by low-threshold muscle afferents (Group I and II). Peak latencies of MDNs in P were shorter than those in A. Intracortical microstimulation (less than 30 microA) in A produced oro-facial movements while stimulation in P did not produce any motor effects.

Animals↗