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Biomedical subjects

Y Kishi

Publications and source records attributed to Y Kishi.

At least 109 records · Page 6Linked to original sources

Midazolam premedication reduces propofol requirements for sedation during regional anesthesia.

PURPOSE: Propofol is often used for sedation during spinal anesthesia. We investigated the effects of midazolam premedication on the propofol requirements and incidence of complications during sedation. METHODS: In a prospective randomized, controlled, and single-blinded study, 50 patients undergoing elective gynecological surgery were randomly divided into control and midazolam groups. Patients in the midazolam group received 2 mg midazolam im 30 min before arrival at the operation room. After spinal anesthesia was instituted with intrathecal injection of hyperbaric tetracaine, we provided sedation using continuous infusion of propofol. The level of sedation was controlled at a level between "eyes closed but rousable to command" and "eyes closed but rousable to mild physical stimulation" by adjusting the infusion rate. During sedation, the propofol requirements and complications were recorded and patients were asked, two hours after the end of operation, whether they remembered intraoperative events. RESULTS: In the midazolam group, the loading dose, steady state infusion rate, and overall infusion rate of propofol were 0.74 mg x kg(-1), 2.86 mg x kg(-1) x hr(-1), and 3.32 mg x kg(-1) x hr(-1), respectively, which were about 17% lower than those in the control group (P<0.05). Moreover, midazolam premedication reduced the incidence of intraoperative memory (P < 0.05), but had no effects on other complications. CONCLUSION: Midazolam premedication reduced propofol requirements and the incidence of intraoperative memory during sedation. These effects on sedation using propofol during spinal anesthesia are considered beneficial for patients.

Adult↗

Effects of acidosis and NO on nicorandil-activated K(ATP) channels in guinea-pig ventricular myocytes.

1. Nicorandil is a hybrid compound of K(+) channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K(+) channel (K(ATP)) in guinea-pig ventricular myocytes using the patch-clamp technique. 2. In whole-cell recordings, external application of 300 microM nicorandil activated K(ATP) in the presence of 2 mM intracellular ATP concentration ([ATP](i)) at external pH (pH(o)) 7. 4, but the activated current was decreased by reducing pH(o) to 6.5 - 6.0. 3. Single-channel recordings of inside-out patches revealed decreased open-state probability (P(o)) of K(ATP) activated by nicorandil with reducing internal pH (pH(i)) from 7.2 to 6.0, whilst the channel activity increased at low pH(i) in the absence of nicorandil. 4. Application of NO donors, 1 mM-sodium nitroprusside (SNP) or -NOR-3 to the membrane cytoplasmic side at pH(i) 7.2 increased the channel activity but decreased it at pH(i) 6.5 - 6.0. Neither removal of the drugs nor application of NO-scavengers reversed depression of channel activity induced by NO-donors. 5. We conclude that an increase in pH(o) and pH(i) depresses rather than stimulates the nicorandil-activated K(ATP). Since NO-donors at low pH(i) exhibited a similar trend, involvement of H(+) and NO interaction can be considered as a mechanism of decreased K(ATP) activated by nicorandil.

Acidosis↗

Donor lymphocyte infusion for treatment of life-threatening respiratory syncytial virus infection following bone marrow transplantation.

We describe two patients who developed respiratory syncytial virus (RSV) pneumonia after BMT. One died of RSV pneumonia after three courses of steroid pulse therapy. Surprisingly, RSV antigen was identified in the bronchoalveolar lavage fluid (BALF) obtained post mortem. Steroid pulse therapy might have suppressed anti-RSV immunity, leading to persistent RSV infection for more than 1 month. The other patient received donor lymphocyte infusions (DLI) for relapsed plasma cell leukemia, while having active RSV pneumonia. His respiratory condition improved after DLI, and RSV antigen disappeared in BALF and nasal swabs. DLI might be effective in cases of life-threatening RSV pneumonia.

Acute Disease↗

Gene expression of antioxidant enzymes in experimental diabetic neuropathy.

Chronic hyperglycemia results in a large deficit in nerve blood flow. Both autoxidative- and ischemia-induced lipid peroxidation occurs, with resultant peripheral sensory neuropathy in streptozotocin-induced diabetes in the rat. Free radical defenses, especially involving antioxidant enzymes, have been suggested to be reduced, but scant information is available on chronic hyperglycemia. We evaluated the gene expression of glutathione peroxidase, catalase, and superoxide dismutase (cuprozinc and manganese separately) in L4,5 dorsal root ganglion (DRG) and superior cervical ganglion, as well as enzyme activity of glutathione peroxidase in DRG and sciatic nerve in experimental diabetic neuropathy of 3 months and 12 months durations. We also evaluated nerve electrophysiology of caudal, sciatic-tibial, and digital nerves. A nerve conduction deficit was seen in all nerves in experimental diabetic neuropathy at both 3 and 12 months. Gene expression of glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in experimental diabetic neuropathy at either 3 or 12 months. Catalase mRNA was significantly increased in experimental diabetic neuropathy at 12 months. Glutathione peroxidase enzyme activity was normal in sciatic nerve. We conclude that gene expression is not reduced in peripheral nerve tissues in very chronic experimental diabetic neuropathy. Changes in enzyme activity may be related to duration of diabetes or due to post-translational modifications.

Animals↗

Supraspinal, not spinal, alpha(2) adrenoceptors are involved in the anesthetic-sparing and hemodynamic-stabilizing effects of systemic clonidine in rats.

UNLABELLED: Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT rauwolscine had no effect. Our data demonstrate that the alpha(2) adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal alpha(2) adrenoceptors were not involved in these effects of clonidine. IMPLICATIONS: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.

Adrenergic alpha-Agonists↗

Ibudilast modulates platelet-endothelium interaction mainly through cyclic GMP-dependent mechanism.

3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast) has been widely used in Japanese clinics for its antiasthmatic and antithrombotic effects. We investigated the mechanisms involved in the antiplatelet effects of the agent, specifically focusing on platelet-endothelium interaction. Ibudilast inhibits both phosphodiesterase (PDE) 3 and 5, the two major PDE isoforms of human platelets, with an IC50 of 31 and 2.2 microM, respectively. Cyclic guanosine monophosphate (GMP) accumulation in washed human platelets exposed to ibudilast alone increased significantly only at high concentrations of the agent (100 microM), whereas > or = 1 microM ibudilast enhanced cyclic GMP levels in the platelets cocultured with bovine aorta endothelial cells (ECs). In contrast, ibudilast enhanced cyclic AMP accumulation only at 100 microM, either with or without ECs. The synergistic effect of ibudilast and EC on cyclic nucleotide accumulation also was demonstrated by the inhibitory capability of the drug and the cells on platelet aggregation. The synergism between ibudilast and aspirin-pretreated ECs was more pronounced than that between ibudilast and N(omega)-nitro-L-arginine (L-NNA)-pretreated ECs. Ibudilast affected neither ATP diphosphohydrolase activity nor NO release from EC up to a concentration of 10 microM. We conclude that ibudilast exhibits antiplatelet properties mainly by inhibiting PDE5 to potentiate antiplatelet function of endothelium-derived NO.

Animals↗

Inflammation and atherosclerosis. Atherosclerotic lesions in Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis, mainly involving the aorta and its main branches as well as the coronary and pulmonary arteries, causing stenosis and/or obstruction due to thrombus formation or dilatation due to aneurysmal formation and/or rupture of the involved arteries. These characteristic anomalies resulted from ischemia of retinal arteries due to the obstruction of cervical vessels. In Western countries this disease is also known as "pulseless disease," because the pulse is frequently absent due to the obstruction of subclavian or branchial arteries. The pathogenesis of this morbid condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Affected areas consist of a mixture of both active, productive inflammatory lesions, and old fibrous lesions. Autoimmune processes stimulated by viral infection and other unknown causative factors may play an important role under these pathophysiological conditions because HLA analysis revealed a statistically significant high frequency of haplotype A24-B52-DR2 in these patients in Japan. Documentation of atherosclerotic complications in young female patients with Takayasu arteritis who are generally free from traditional atherosclerosis risk factors may be clinical evidence that inflammation is indeed an important risk factor in atherogenesis.

Arteries↗

Consequences of interaction of a lipophilic endotoxin antagonist with plasma lipoproteins.

E5531, a novel synthetic lipid A analogue, antagonizes the toxic effects of lipopolysaccharide, making it a potential intravenously administered therapeutic agent for the treatment of sepsis. This report describes the distribution of E5531 in human blood and its activity when it is associated with different lipoprotein subclasses. After in vitro incubation of [(14)C]E5531 with blood, the great majority (>92%) of material was found in the plasma fraction. Analysis by size-exclusion and affinity chromatographies and density gradient centrifugation indicates that [(14)C]E5531 binds to lipoproteins, primarily high-density lipoproteins (HDLs), with distribution into low-density lipoproteins (LDLs) and very low density lipoproteins (VLDLs) being dependent on the plasma LDL or VLDL cholesterol concentration. Similar results were also seen in a limited study of [(14)C]E5531 administration to human volunteers. The potency of E5531 in freshly drawn human blood directly correlates to increasing LDL cholesterol levels. Finally, preincubation of E5531 with plasma or purified lipoproteins indicated that binding to HDL resulted in a time-dependent loss of drug activity. This loss in activity was not observed with drug binding to LDLs or to VLDLs or chylomicrons. Taken together, these results indicate that E5531 binds to plasma lipoproteins, making its long-term antagonistic potency dependent on the plasma lipoprotein composition.

Cholesterol↗

Novel actin cytoskeleton: actin tubules.

In spores of Dictyostelium discoideum three actin filaments are bundled to form a novel tubular structure and the tubules are then organized into rods. These tubular structures we will term actin tubules. Actin tubules are reconstructed from the supernatant of spore homogenates, while the usual actin filaments were bundled after incubation of supernatants from growing cells. Alpha-actinin, ABP-120 and EF-1alpha are not essential for rod formation. Cofilin is a component of the cytoplasmic rods but few cofilin molecules are included in the nuclear rods. The viability of spores lacking actin rods is very low, and the spore shape is round instead of capsular. The rods can be fragmented by pressure, indicating that the rods may be effective in absorbing physical pressure. The complex organization of actin filaments, actin tubules and rods may be required for spores to achieve complete dormancy and maintain viability.

Actin Cytoskeleton↗

[Anesthesia for MIDCAB (minimally invasive direct coronary bypass) in a patient with Tangier disease: a case report].

Tangier disease is a rare, autosomally-inherited disorder of lipoprotein metabolism characterized by absence or marked deficiency of normal high density lipoprotein (HDL) cholesterol in plasma resulting in the accumulation of cholesteryl esters in various organs. The patient was a 55-yr-old male diagnosed as Tangier disease 16 years before. He had angina on exercise and his coronary angiogram revealed triple vessel disease including left main trunk (LMT) lesion. Stenosis of the right coronary artery was treated by percutaneous transluminal coronary angioplasty (PTCA). He was scheduled for a MIDCAB for further PTCA to be performed to relieve the stenosis of LMT. Preoperative laboratory data and physical examination showed total cholesterol 36 mg.dl-1, HDL-cholesterol 2 mg.dl-1, apoprotein A-I not-detected, pancytopenia, hyperplastic orange tonsils, splenomegaly and hepatomegaly. Clonidine 0.225 mg was orally given as a preanesthetic medication. Anesthesia was induced with fentanyl and midazolam and maintained with propofol, sevoflurane and supplemental fentanyl. Nitroglycerin and diltiazem were infused continuously. ST segment was elevated transiently during the clamping of the left anterior descending branch. Hemodynamic parameters were stable during the operation. He was extubated 2 hours after the end of the operation. No significant changes were found in postoperative EKG, total cholesterol, HDL-cholesterol and triglyceride. Perioperative course was uneventful.

Anesthesia↗

[Effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia].

Twenty patients were prospectively and randomly studied to investigate effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia. After establishment of spinal anesthesia, patients were randomly assigned to one of the following two groups, i.e. conventional continuous infusion group (Cont group) and target-controlled infusion group (TCI group). In the Cont group, propofol was started at a rate of 6 mg.kg-1.hr-1 until response to command disappeared. In the TCI group, the initial target concentration of propofol was set at 1.2 micrograms.ml-1 until response to command disappeared. Thereafter infusion rate or target concentration was adjusted to maintain Mackenzie's score at 3 or 4. Predicted concentration of propofol was 1.2 +/- 0.01 micrograms.ml-1 at induction of sedation and 1.2 +/- 0.11 micrograms.ml-1 during stable sedation in the TCI group. Satisfaction VAS, anxiety VAS, discomfort VAS, sedation score and times of changing infusion condition were similar in both groups. Total dose of propofol was significantly less in the TCI group. In conclusion, quality of sedation and ease of control of sedation were comparable in both groups and continuous infusion method is simple.

Adult↗

Toward creation of a universal NMR database for the stereochemical assignment of acyclic compounds: the case of two contiguous propionate units.

[formula: see text] Using triol 1 as a representative example of natural products containing two contiguous propionate units, 13C and 1H NMR databases for the stereochemical assignment of acyclic compounds have been created. Chemical shift increments due to the presence of additional functional groups as well as solvent effects are discussed.

Databases, Factual↗

Synthesis and structure of tolyporphin A O,O-diacetate.

[formula: see text] The revised structure of tolyporphin A O,O-diacetate (2b) was synthesized by assembling fragments 4, 5, and 12. The synthetic substance was found to be identical to the O,O-diacetate derived from natural tolyporphin A in every respect, thus establishing the relative and absolute configurations of this natural product.

Molecular Structure↗