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Biomedical subjects

Y Kotake

Publications and source records attributed to Y Kotake.

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

Inhibition of the cytokine-mediated inducible nitric oxide synthase expression in rat insulinoma cells by phenyl N-tert-butylnitrone.

Cytokines and nitric oxide (NO) have been implicated in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We have shown that the spin-trapping agent phenyl N-tert-butylnitrone (PBN) protects against streptozotocin (STZ)-induced IDDM in mice. In order to gain more insights into the mechanism(s) of the protective action of PBN against IDDM, we have investigated the effect of this compound on the cytokine-induced NO generation (measured as nitrite) in rat insulinoma RIN-5F cells. Our results demonstrate that PBN cotreatment prevents the generation of nitrite by RIN-5F cells induced by treatment with tumor necrosis factor-alpha, interleukin 1beta, and interferon-gamma in a dose-dependent fashion. The generation of NO as a result of cytokine treatment and the inhibitory effect of PBN were further confirmed by electron paramagnetic resonance spectroscopy. Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase (iNOS), abolished the cytokine-induced nitrite generation whereas N-nitro-l-arginine, an inhibitor more selective for other NOS isoforms, was significantly less effective. Western and Northern analyses demonstrated that PBN inhibits the cytokine-mediated expression of iNOS at the transcriptional level. Cytokine-induced nitrite formation was also inhibited by the two antioxidant agents alpha-lipoic acid and N-acetylcysteine. These results indicate that PBN protects against IDDM at least in part by prevention of cytokine-induced NO generation by pancreatic beta-cells.

Acetylcysteine↗
PubMed2000

Surgery for pulmonary metastases from colorectal carcinoma.

BACKGROUND: This study aims to clarify which patients would benefit by surgery for pulmonary metastases from colorectal carcinoma. METHODS: A retrospective study was undertaken in 25 patients who had undergone complete resection. In all cases, prethoracotomy carcinoembryonic antigen (CEA) level was measured and mediastinal or hilar lymph nodes were histologically examined. RESULTS: Overall 5-year survival was 39.2%. The 5-year survival rate for patients with a normal CEA level was 61.1%, as compared with 19.0% for patients with an elevated CEA level (p = 0.0423). The 5-year survival rate for patients without a lymph node metastasis was 49.5%, as compared with 14.3% for patients with a lymph node metastasis (p = 0.0032). No lymph node metastasis was a predictor of longer survival by univariate and multivariate analyses. The primary site, disease-free interval, and number and size of the metastasis were not significant prognostic factors. CONCLUSIONS: A resection for pulmonary metastasis from colorectal carcinoma is effective in patients with a normal CEA level and without a lymph node metastasis.

Adult↗
PubMed2000

Hypermagnesemia-induced cardiopulmonary arrest before induction of anesthesia for emergency cesarean section.

We describe a 42-yr-old woman scheduled for emergency cesarean section who had sudden cardiopulmonary arrest just before induction of general anesthesia. Hypermagnesemia, caused by accidental overdose of magnesium sulfate during transportation to the operating room, was the primary cause of this life-threatening event. Anesthetic management after such events and a brief summary of the literature regarding iatrogenic hypermagnesemia in obsteric patients are provided.

Adult↗
PubMed2000

Additional droperidol, not butorphanol, augments epidural fentanyl analgesia following anorectal surgery.

STUDY OBJECTIVE: To examine the effects of additional droperidol or butorphanol to epidural fentanyl infusion on postsurgical analgesia. DESIGN: Prospective, randomized, single blinded clinical study. SETTING: University-affiliated medical center. PATIENTS: 60 ASA physical status I and II patients undergoing anorectal surgery by one surgeon. INTERVENTIONS: Patients were randomly allocated to the following groups according to the medication that was continuously administered into the epidural space: 1) Group C (n = 20) received 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; 2) Group D (n = 20) received 2.5 mg droperidol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; and 3) Group B (n = 20) received 2 mg butorphanol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine over 24 hours postoperatively. MEASUREMENTS AND MAIN RESULT: Postsurgical analgesia and the incidence of fentanyl-related complications, such as nausea/vomiting, somnolence, pruritus, and respiratory depression, were assessed for 24 hours postoperatively. At 16 and 24 hours after surgery, 75% of patients in Group D reported no pain versus 35% in Group C (p < 0.05). In addition, the overall visual analogue scale examined at 24 hours was significantly lower in Group D than that in Group C (22 +/- 17 mm vs. 44 +/- 22 mm, respectively; p < 0.05). Simultaneously, the incidence of postoperative nausea/vomiting was lower in Group D compared with Group C (20% vs. 60%; p < 0.05). On the other hand, butorphanol did not modify the analgesic effects or complications of epidural fentanyl infusion. CONCLUSION: In this study population, additional droperidol, not butorphanol, improved postsurgical analgesia accompanied by less incidence of nausea/vomiting during epidural fentanyl administration.

Adjuvants, Anesthesia↗
PubMed2000

Dopamine transporter and catechol-O-methyltransferase activities are required for the toxicity of 1-(3',4'-dihydroxybenzyl)-1,2,3, 4-tetrahydroisoquinoline.

1-(3',4'-Dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline [3', 4'DHBnTIQ (1)] is an endogenous parkinsonism-inducing substance. It is taken up into dopaminergic neurons via the dopamine transporter, inhibits mitochondrial respiration, and induces parkinsonism in mice. We synthesized four derivatives [aromatized, N-methylated, N-methyl-aromatized, and O-methylated (2-5, respectively)] and studied the cellular uptake and cytotoxicity of 1-5, as well as the metabolism of 1. All except the O-methyl derivative (5) were specifically taken up by the dopamine transporter, but 1 was taken up most efficiently. Relative to 1, oxidation reduced v(max), N-methylation markedly increased K(m), and O-methylation eliminated the uptake activity. The cytotoxicity of 1-5 was examined in a mesencephalic cell primary culture. Compound 1 reduced cell viability by nearly 80% at 100 microM, but the other compounds had little or no effect on cell viability. In vivo and in vitro studies revealed that 1 was O-methylated by soluble catechol-O-methyltransferase (COMT). Aromatization and N-methylation of 1 were not observed. We found that dopamine transporter inhibitors and a COMT inhibitor each blocked the cytotoxicity of 1, indicating that uptake and O-methylation are both necessary for neurotoxicity. Thus, we consider that 1 is taken up into dopaminergic neurons via the dopamine transporter and then converted by COMT to 5, which has cytotoxic and parkinsonism-inducing activities.

Animals↗
PubMed2000

Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria.

Removal of choline from the diet results in accumulation of triglycerides in the liver, and chronic dietary deficiency produces a non-genotoxic model of hepatocellular carcinoma. An early event in choline deficiency is the appearance of oxidized lipid, DNA and protein, suggesting that increased oxidative stress may facilitate neoplasia in the choline deficient liver. In this study, we find that mitochondria isolated from rats fed a choline-deficient, L-amino acid defined diet (CDAA) demonstrate impaired respiratory function, particularly in regard to complex I-linked (NADH-dependent) respiration. This impairment in mitochondrial electron transport occurs coincidentally with alterations in phosphatidylcholine metabolism as indicated by an increased ratio of long-chain to short-chain mitochondrial phosphatidylcholine. Moreover, hydrogen peroxide (H(2)O(2)) generation is significantly increased in mitochondria isolated from CDAA rats compared with mitochondrial from normal rats, and the NADH-specific yield of H(2)O(2) is increased by at least 2.5-fold. These findings suggest an explanation for the rapid onset of oxidative stress and energy compromise in the choline deficiency model of hepatocellular carcinoma and indicate that dietary choline withdrawal may be a useful paradigm for the study of mitochondrial pathophysiology in carcinogenesis.

Animals↗
PubMed2000

[Changes of vascular reactivity following esophagectomy measured by near-infrared spectroscopy].

We examined the alterations of peripheral vascular responses following ischemic insult during perioperative period of esophagectomy. Increase of palm blood flow after vascular occlusion, i.e., reactive hyperemia (RH), measured by near-infrared spectroscopy (NIRS) was employed to assess forearm vascular responses. The measurements of RH were performed in esophagectomized patients (n = 12) before induction of anesthesia and postoperatively until the next day of extubation in comparison with normal volunteers (n = 11). After esophagectomy, the RH, which was comparable with those in volunteers, was depressed by 50% on 1 POD, and did not recover until the third POD. In particular, patients receiving laparoscopy-assisted surgery showed less decrease of RH than those receiving the standard open laparotomy. These results suggest that vascular responses to increase blood flow against ischemic insult is depressed following esophagectomy.

Adult↗
PubMed2000

[Successful TS-1 therapy in a patient with non-resectable gastric cancer and renal dysfunction].

A 73-year-old woman presented to our hospital with epigastric pain and swelling of the left upper limb. Enlarged lymph nodes with adhesion were palpable in the left cervical region and supraclavicular fossa. Tests were performed with the thought that the left upper limb swelling was secondary to venous compression by the enlarged lymph nodes. Gastroscopy detected a torose lesion on the anterior wall at the gastric angle and biopsy revealed that it was moderately differentiated adenocarcinoma. MRI showed metastasis to the sixth cervical vertebra and the first thoracic vertebra. Based on these findings, she was diagnosed as having progressive gastric cancer with metastasis to Virchow's lymph node and the cervical and thoracic vertebrae. Because it was considered impossible to perform radical gastrectomy, chemotherapy was given. Since renal dysfunction was suggested by a serum Cr of 1.5 mg/ml and a Ccr of 26.2 ml/min, TS-1 was administered at a lower dose (50 mg/day for 4 weeks) than usual, followed by 2 weeks off therapy to complete 1 course. During TS-1 therapy, the plasma 5-FU concentration at 4 h was 129.5 ng/ml, indicating that an effective plasma level of the drug was achieved. TS-1 therapy was considered effective because it reduced the diameter of the primary tumor and the lymph node metastasis, with only mild adverse reactions including myelosuppression.

Adenocarcinoma↗
PubMed1999

Regional distribution of parkinsonism-preventing endogenous tetrahydroisoquinoline derivatives and an endogenous parkinsonism-preventing substance-synthesizing enzyme in monkey brain.

1,2,3,4-Tetrahydroisoquinoline (TIQ) and 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), which exist in the brain of several mammalian species, are parkinsonism-inducing substances, and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), which is enzymatically synthesized in rat brain, is a parkinsonism-preventing substance. In this study, we examined the regional distribution of contents of TIQ, 1MeTIQ, and 1BnTIQ, and activity of 1MeTIQ-synthesizing enzyme in monkey brain. The TIQ and 1BnTIQ contents in cerebrum and substantia nigra, and the 1MeTIQ contents in striatum and substantia nigra were higher than those in other brain regions, and 1MeTIQ-synthetic activity was high in cerebrum and thalamus. We speculate that 1MeTIQ-synthesizing enzyme may play an important role in idiopathic Parkinson's disease.

Animals↗
PubMed1999

Phenyl-N-tert-butylnitrone demonstrates broad-spectrum inhibition of apoptosis-associated gene expression in endotoxin-treated rats.

Systemic exposure to gram-negative bacterial substances such as lipopolysaccharide (LPS, or endotoxin) induces an uncontrolled, massive inflammatory reaction which culminates in multiple system organ failure and death. Septic shock often does not respond to corticosteroids; however, certain low-molecular-weight antioxidant compounds have been discovered to possess potent anti-inflammatory action, and some of these novel compounds can rescue animals from experimentally induced septic shock. Phenyl-N-tert-butylnitrone (PBN) is the archetype of the nitrone class of antioxidants which we have previously shown to suppress LPS-induced cytokine biosynthesis in vivo. Using a multiprobe ribonuclease protection assay, we now demonstrate the ability of PBN to suppress proapoptotic gene expression in the LPS-induced model of endotoxic shock. The broad-spectrum gene-suppressive affects of PBN are discussed in the context of inflammatory signal transduction and models are proposed to explain why certain antioxidants may also possess anti-inflammatory and antiapoptotic properties.

Animals↗
PubMed1999

Expression of cytokines and activation of transcription factors in lipopolysaccharide-administered rats and their inhibition by phenyl N-tert-butylnitrone (PBN).

The spin-trapping compound phenyl N-tert-butylnitrone (PBN) affords protection from the lethality of septic shock in rodents. Previous studies have shown that PBN elicits its protection by inhibiting inducible nitric oxide synthase (iNOS) induction. In the present study, using the lipopolysaccharide (LPS) rat septic shock model, we determined the expression of various cytokine genes (tumor necrosis factor (TNF)-alpha, TNF-beta, interferon (IFN)-gamma, interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-10) and the activation of transcription factors nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) in the liver tissue, 30 min and 3 h after LPS administration. The effects of PBN preadministration on the production levels were also investigated. The results show that LPS (4 mg/kg, ip) induced the production of the cytokine genes and increased the nuclear protein level of NF-kappaB within 30 min after LPS administration. Preadministration of PBN (150 mg/kg, ip) significantly down-regulated the production of cytokine genes (TNF-alpha by 94%, IL-1 by 63%, and IL-1 by 70%) and reduced the nuclear protein level of NF-kappaB by 75% and AP-1 by 72% at 3 h after LPS injection. These results demonstrate that PBN, in addition to its iNOS induction inhibition, also has multiple anti-inflammatory effects in septic shock, via modulation of the production of the key inflammatory mediators.

Animals↗
PubMed1999

Continuous monitoring of in vivo nitric oxide formation using EPR analysis in biliary flow.

A method to continuously monitor the nitric oxide (NO) level in anesthetized rats, using an in vivo trapping reaction of NO by iron-dithiocarbamate complex, is reported. Previously, we developed a method of monitoring NO in bile samples containing an NO complex excreted from the liver (Anal. Biochem. 243, 8-14, 1996). In the present study, we modified the method so that the bile flows directly through the EPR sample cell. Rats were injected with low doses of lipopolysaccharide (LPS) to induce NO formation and were later anesthetized. After cannulation, the bile duct was connected to the inlet of the EPR sample cell and the trapping agent iron complex of D-N-methylglucamine dithiocarbamate (MGD-Fe) was administered. The EPR signal level from NO complex of MGD-Fe in the flowing bile was continuously monitored. Using this method, immediate changes in in vivo NO level in rats were observed following administration of drugs that can affect NO formation. In addition, a continuous intravenous saline containing MGD-Fe made the EPR signal level stable and improved animal condition as well as survival time. Therefore, this method has two merits; (1) one can continuously monitor NO formation until it reaches the maximum level; (2) a rapid change in NO level after intervention can be followed. Using this method, we tested the effect of the substrate L-arginine and inhibitors for NO synthase activity and NO synthase induction. The sensitivity of the present method was tested by monitoring NO formation in rats after exposure to ionizing radiation.

Animals↗
PubMed1999

High-performance liquid chromatography study of the pharmacokinetics of various spin traps for application to in vivo spin trapping.

In vivo spin trapping is potentially a very useful tool to investigate the role of free radicals in physiologic processes and disease development. Unfortunately, knowledge on the stability and distribution of spin traps in living systems is limited. Therefore, in our study, we selected 11 acyclic and cyclic nitrone spin traps with diverse properties to determine their pharmacokinetics in mice. At varying times after intraperitoneal administration, we measured the concentration of the spin traps in the liver, heart, and blood. Our results showed that most spin traps were rapidly absorbed and were approximately evenly distributed throughout the mouse body. It was also found that most of the traps were relatively stable in vivo with more than half of the injected amount still available for spin trapping free radicals after an hour. Two of the 11 tested spin traps, however, decomposed after injection. These results indicate that for a successful in vivo spin trapping experiment, the stability of the spin trap is not of major concern, but the time course of distribution may be important.

Animals↗
PubMed1999

Trapping of free radicals with direct in vivo EPR detection: a comparison of 5,5-dimethyl-1-pyrroline-N-oxide and 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide as spin traps for HO* and SO4*-.

To spin trap hydroxyl radical (HO*) with in vivo detection of the resultant radical adducts, the use of two spin traps, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) (10 mmol/kg) has been compared. In mice treatment with 5-aminolevulinic acid and Fe3+ resulted in detection of adducts of hydroxyl radicals (HO*), but only with use of DEPMPO. Similarly, 'HO* adducts' generated via nucleophilic substitution of SO4*- adducts formed in vivo could be observed only when using DEPMPO as the spin trap. The reasons for the differences observed between DEPMPO and DMPO are likely due to different in vivo lifetimes of their hydroxyl radical adducts. These results seem to be the first direct in vivo EPR detection of hydroxyl radical adducts.

Animals↗
PubMed1999

Purification of P0 myelin glycoprotein by a Cu2+-immobilized metal affinity chromatography.

P0 is an abundant myelin glycoprotein of peripheral nerves of vertebrates. Various point mutations of this protein are responsible for hereditary neuropathies. In this paper we described purification of P0 glycoprotein using SDS and a metal chelate affinity chromatography. Purified myelin fraction from bovine spinal roots in 0.5% SDS, 0.5 M NaCl, 50 mM Tris-HCl, pH 7.4 is filtered and applied directly to the Cu2+-immobilized affinity chromatography column, equilibrated with the same buffer. After eluting a void volume (or pass through) fraction, P0 protein was eluted by the same buffer but without salt. To remove contamination from the eluent, further purification is continued on a Concanavalin-A coupled agarose column. We purify within two days, 30 mg of P0 protein of apparent molecular weight 27 kDa. The method can be used to purify recombinant or mutated P0 protein found in severe pathologies.

Animals↗
PubMed1999

Permissive hypercapnia during thoracic anaesthesia.

BACKGROUND: While permissive hypercapnia is commonly practised in critical care, it remains unclear if the comparable manoeuvres are clinically acceptable during anaesthesia. This retrospective study aimed at describing the anaesthetic implications of hypercapnia associated with deliberate hypoventilation during thoracic surgery in patients with severe emphysema. METHODS: Thirteen patients with emphysema who required thoracic surgery under similar anaesthesia were reviewed: 3 patients were managed to maintain normocapnia (normocapnia group) whereas 10 patients developed hypercapnia (PaCO2 >70 mmHg) as a result of restricting peak airway pressures (hypercapnia group). RESULTS: In the normocapnia group (PaCO2: 45+/-1 mmHg, mean+/-SD), no event which required therapeutic intervention during the surgery was seen, whereas 2 of 3 patients showed postoperative air leakage which persisted over 5 days. In the hypercapnia group, the maximum PaCO2 during anaesthesia ranged between 70 mmHg and 135 mmHg (98-21 mmHg). During anaesthesia, all 10 patients required inotropic support to prevent hypotension, 4 patients required tracheal gas insufflation of oxygen to the operated lung to avoid hypoxaemia and 3 patients required lidocaine to treat ventricular arrhythmia. However, the trachea was extubated in the operation theatre in 9 of 10 patients and no organ dysfunction was observed postoperatively. Four patients showed postoperative air leak on the first postoperative day, one of which persisted over 5 days. CONCLUSION: Although there are some limitations, this preliminary study indicates that hypercapnia around 100 mmHg during anaesthesia for thoracic surgery may not be associated with serious consequences.

Aged↗