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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 91 records · Page 5Linked to original sources
PubMed2000

Blunt carotid artery injury after accidental neck compression: report of a case.

Almost all cases of carotid artery injury are precipitated by a high-energy impact such as motor vehicle accidents or gunshot wounds, and are usually diagnosed using angiography. We report herein a case of carotid artery injury induced by a low-energy insult with rare clinical signs which was diagnosed using ultrasonography as well as angiography. A 37-year-old man sustained an accidental compression of the neck and was transferred to our emergency room. Horner's syndrome and phrenic nerve palsy were detected on the left side. Ultrasonography demonstrated two sites of injury with an intimal flap of the distal left common carotid artery as well as angiography. The patient was placed on anticoagulants and was discharged on the 10th hospital day with both Horner's syndrome and phrenic nerve palsy. This case suggests that surgeons should investigate any possible carotid artery injury, even after low-velocity injuries such as compression of the neck, and therefore an ultrasonic examination should be performed at the initial evaluation and at follow-up studies. In addition, further investigations are also called for to investigate the utility of anticoagulation in the treatment of carotid artery injury.

Accidents, Occupational↗
PubMed2000

Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.

BACKGROUND/AIM: Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS: Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS: Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day. CONCLUSION: The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.

Adult↗
PubMed2000

Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction.

In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9 microM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis.

Animals↗
PubMed2000

Sustained viral response is rarely achieved in patients with high viral load of HCV RNA by excessive interferon therapy.

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50-94% of patients with < or =2 x 10(4) copies/ml (competitive RT-PCR) or <100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients with > or =2 x 10(5.5) copies/ml (competitive RT-PCR) or >200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that with < or =900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100-200 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with <100, 100-200, and >200 x 10(3) copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 x 10(3) copies/ml of HCV RNA.

Adolescent↗
PubMed2000

Determination of the optimal cut-off value for the [13C]-urea breath test based on a Helicobacter pylori-specific polymerase chain reaction assay.

BACKGROUND: This study was conducted to determine the optimal cut-off value and breath sample collection time for the [13C]-urea breath test based on the assessment of Helicobacter pylori status with a gastric juice-based polymerase chain reaction (PCR) assay. METHODS AND RESULTS: A total of 104 patients took 100 mg [13C]-urea orally and breath samples were collected at 5, 10, 20, 30 and 60 min. The increment of 13CO2:12CO, ratio from the baseline (delta13C) was measured using a laser spectroanalyser. The PCR assay was positive in 63 and negative in 41 patients. The optimal cut-off value of delta13C was calculated for each sample collection time so that the distance from the geometric mean value among Helicobacter pylori-positive patients and that from the arithmetic mean value among negative patients were simultaneously maximized. The cut-off value of 2.7% at 20 min had the longest distance, being separated by 3.16 SD from the two mean values. Using this cut-off value, the urea breath test showed 100% specificity and 98% sensitivity for the diagnosis of Helicobacter pylori infection.

Breath Tests↗
PubMed2000

Thioredoxin inhibits tumor necrosis factor- or interleukin-1-induced NF-kappaB activation at a level upstream of NF-kappaB-inducing kinase.

Gene induction by tumor necrosis factor-alpha (TNFalpha) or interleukin-1beta (IL-1beta) is mediated in part by activation of the transcription factor nuclear factor kappaB (NF-kappaB), and requires signal adaptor molecules such as TNF receptor-associated factor (TRAFs). The latter interact with the NF-kappaB-inducing kinase (NIK), which is believed to be part of the IkappaB kinase complex. Although the precise mechanism is to be elucidated, it is well-known that antioxidant treatments inhibit the inflammatory cytokine-induced NF-kappaB activation. Thioredoxin (TRX) is a 12-kDa endogenous protein that regulates various cellular functions by modulating the redox state of proteins, overexpression of this molecule inhibits NF-kappaB activation. To elucidate the roles of TRX in the signal transduction of the cytokines, we investigated the effects of TRX on NF-kappaB activation induced by cytokine treatment or by overexpression of the signaling molecules. Our data show that TRX treatment inhibits NF-kappaB-dependent transcription at the level of downstream of TRAFs and upstream of NIK: TRX inhibited TRAF2-, TRAF5-, and TRAF6-induced NF-kappaB activation but does not inhibit NIK-, IKKalpha-, and MEKK-induced activation. In addition, we show that TRX inhibits NF-kappaB activation in a manner different from that for SAPK (stress activated protein kinase) inhibition.

Acetylcysteine↗
PubMed2000

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.

Alprostadil↗
PubMed2000

Interaction of local anaesthetics with recombinant mu, kappa, and delta-opioid receptors expressed in Chinese hamster ovary cells.

Local anaesthetics potentiate epidural or intrathecal opioid analgesia via a poorly defined mechanism. In this study, we have examined the interaction of local anaesthetics (lidocaine, bupivacaine and its optical isomers, tetracaine, procaine and prilocaine) with recombinant mu-, kappa-, and delta-opioid receptors expressed in Chinese hamster ovary cells (CHO-mu, kappa, and delta, respectively). Lidocaine produced a concentration-dependent displacement of radiolabelled opioid antagonist [3H]diprenorphine ([3H]DPN) binding with the following rank order of inhibitor constant (Ki): kappa (210 microM) > mu (552 microM) > delta (1810 microM). Procaine, prilocaine, tetracaine and bupivacaine also displaced [3H]DPN binding in CHO-mu with Ki values of 244, 204, 43 and 161 microM respectively. Lidocaine produced a concentration-dependent and naloxone-insensitive inhibition of cAMP formation in all cell lines including untransfected cells. Concentration producing 50% inhibition of maximum was mu, 1.32 mM; kappa, 2.41 mM; delta, 1.27 mM; untransfected, 2.78 mM. When lidocaine (300 microM) was co-incubated with spiradoline (kappa-selective) and [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO mu-selective) in CHO-kappa and mu cells we did not observe an additive interaction for cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the kappa receptor. This study suggests that clinical concentrations of local anaesthetics interact with mu and kappa but not delta opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical setting does not occur at the cellular level.

Anesthetics, Local↗
PubMed2000

Inhibitory effects of intravenous anaesthetic agents on K+-evoked norepinephrine and dopamine release from rat striatal slices: possible involvement of P/Q-type voltage-sensitive Ca2+ channels.

The role of the voltage-sensitive Ca2+ channel (VSCC) as a target for anaesthetic action remains controversial. In this study we characterized the VSCC subtypes involved in K+-evoked norepinephrine and dopamine release from rat striatal slices and used this model system to examine the effects of a range of i.v. anaesthetics on release. Nifedipine (L-channel-selective), omega-conotoxin GVI(A) (N-channel-selective), omega-agatoxin IV(A) (P-channel-selective), omega-conotoxin MVIIc (P/Q-channel-selective) and Cd2+ (non-selective), along with alphaxalone, propofol and ketamine, were used in various combinations. Omega-Agatoxin IV(A), omega-conotoxin MVIIc and Cd2+ fully (100%) inhibited norepinephrine and dopamine release. Clinically achievable concentrations of alphaxalone inhibited norepinephrine and dopamine release, with concentrations producing 25 and 50% inhibition (IC25 and IC50) of the maximum of 2.1 and 7.8 microM respectively for norepinephrine and 2.9 and 7.2 microM for dopamine. The effects of propofol were observed at the top of the clinical range and those of ketamine exceeded this range. In addition, IC50 values for alphaxalone in the presence and absence of nifedipine and omega-conotoxin GVI(A) did not differ from the control. Our data suggest that clinically achievable concentrations of alphaxalone and propofol inhibit norepinephrine and dopamine release, which is mediated predominantly through P/Q-type VSCCs, suggesting a role for these channels in anaesthetic action.

Anesthetics, Intravenous↗
PubMed2000

Milrinone attenuates serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

UNLABELLED: We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg. kg(-1). h(-1)). Bronchoconstriction and PH were elicited by 5HT (10 microg/kg + 1.0 mg. kg(-1). h(-1)). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 microg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 microg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% +/- 27% and decreased percentage of bronchial cross-sectional area to 52% +/- 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED(50) in microg/kg) of milrinone for bronchoconstriction: 4.32 +/- 0.13 (47.6) was significantly smaller than that for PH: 3.84 +/- 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 microg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by beta-adrenoceptor activation because beta-blocker did not antagonize. IMPLICATIONS: We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by beta-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.

Animals↗
PubMed2000

A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs.

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 microg/kg + 1 mg x kg(-1) x h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 microg/kg) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (> or =100 microg/kg) and aminophylline (> or =10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.

Adrenergic beta-Antagonists↗
PubMed2000

Reversal of P-glycoprotein and multidrug-resistance protein-mediated drug resistance in KB cells by 5-O-benzoylated taxinine K.

A newly synthesized taxoid originally from the Japanese yew Taxus cuspidata, 5-O-benzoylated taxinine K (BTK) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein (MRP)-mediated multidrug resistance. BTK reversed the resistance to paclitaxel, doxorubicin (ADM), and vincristine (VCR) of KB-8-5 and KB-C2 cells that overexpress P-gp by directly interacting with P-gp. BTK also moderately reversed the resistance to ADM of KB/MRP cells that overexpress MRP. However, BTK neither inhibited the transporting activity of MRP nor reduced intracellular glutathione levels in KB/MRP cells. BTK shifted the distribution of ADM in KB/MRP cells from punctate cytoplasmic compartments to the nucleoplasm and cytoplasm by inhibiting acidification of cytoplasmic organelles. These two functions of BTK make it able to reverse both P-gp- and MRP-mediated MDR. BTK in combination with ADM should be useful for treating patients with tumors that overexpress both P-gp and MRP.

ATP Binding Cassette Transporter, Subfamily B↗