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Biomedical subjects

Shigeru Saito

Publications and source records attributed to Shigeru Saito.

At least 127 records · Page 7Linked to original sources

The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats.

UNLABELLED: The effects of volatile anesthetics on nonadrenergic, noncholinergic (NANC) transmission mediated by calcitonin gene-related peptide (CGRP) are unclear. We studied the effects of isoflurane, halothane, and sevoflurane on NANC depressor responses to electrical spinal cord stimulation in pithed rats whose mean arterial blood pressure was maintained near 120 mm Hg by continuous infusion of methoxamine. Autonomic outflow was blocked by hexamethonium. After 30 min of inhalation of different concentrations of anesthetics, spinal cord stimulation at the lower thoracic level (10 V at 4 Hz; duration, 1 ms) was applied for 30 s to induce a NANC depressor response. Isoflurane at 2% and halothane at 1.5% attenuated NANC depressor responses significantly, whereas isoflurane at 1%, halothane at 0.75%, and sevoflurane at 2% or 4% did not. Volatile anesthetics did not attenuate the release of CGRP after spinal cord stimulation, whereas isoflurane at 2% and halothane at 1.5% significantly inhibited depressor responses to exogenously administered CGRP. Sevoflurane at 4% did not significantly affect CGRP-induced depressor responses. Thus, isoflurane and halothane at large concentrations attenuate NANC depressor responses by attenuating the depressor action of CGRP, not CGRP release. IMPLICATIONS: The anesthetics isoflurane and halothane attenuate nonadrenergic, noncholinergic depressor responses mediated by calcitonin gene-related peptide in the rat without affecting the release of the peptide.

Anesthetics, Inhalation↗

Anesthetic management for clipping a giant basilar artery aneurysm with moderate hypothermia, extracorporeal circulation assistance, and propofol infusion.

A 65-year-old female patient underwent surgery to clip a giant basilar artery aneurysm with closed-chest extracorporeal circulation using femorofemoral bypass. Moderate hypothermia (27 degrees C-30 degrees C), retention of spontaneous circulation, and propofol infusion (3-5 mg. kg(-1). h(-1)) were used under general anesthesia. Blood outflow via femoral vein was sufficient to maintain cardiopulmonary bypass and to induce hypothermia. Hemodynamics were controlled with dopamine and noradrenaline. In this case, extracorporeal circulation under moderate hypothermia was used to assist rather than substitute for spontaneous circulation, and spontaneous circulation was maintained at all times. We think that this method had advantages over deep hypothermic circulatory arrest with regard to intraoperative risks and postoperative complications.

Aged↗

End-tidal carbon dioxide monitoring stabilized hemodynamic changes during ECT.

Accumulation of carbon dioxide (CO2) can disturb systemic and cerebral hemodynamics in patients receiving electroconvulsive therapy (ECT). The purpose of this study was to identify the effects of end-tidal CO2 monitoring on hemodynamic changes in patients who received ECT under propofol anesthesia. ECT was prescribed to 40 patients under propofol anesthesia. Ventilation was assisted using a face mask and 100% oxygen, with or without end-tidal CO2 monitoring. Heart rate was significantly increased in patients without end-tidal CO2 monitoring at 1 to 5 minutes after electrical stimulation (p < 0.01). Mean arterial blood pressure and middle cerebral artery blood flow velocity in the group without end-tidal CO2 monitoring were significantly larger than the values in the group with the monitor at 1 to 5 minutes after electrical stimulation. Arterial CO2 tension in the group without end-tidal CO2 monitoring was larger than the value in the group with the monitoring at 1 minute (45+/-5 mm Hg with the monitor and 56+/-8 without the monitor) and 5 minutes (37+/-4 mm Hg with the monitor and 51+/-8 without the monitor) after electrical stimulation (p < 0.01). Application of end-tidal CO2 monitoring is considered beneficial for safe and effective anesthesia management of patients undergoing ECT, especially patients with an intracranial disorder or ischemic heart disease.

Adult↗

Benefits of the laryngeal mask for airway management during electroconvulsive therapy.

Accumulation of carbon dioxide (CO2) can disturb systemic hemodynamics and increase the seizure threshold in patients receiving electroconvulsive therapy (ECT). The purpose of this study was to investigate the effects of the laryngeal mask on blood gas, hemodynamics, and seizure duration during ECT under propofol anesthesia. Ventilation was assisted using either a face mask (n=23) or laryngeal mask (n=23) and 100% oxygen. There was no significant difference in PaO2 between the two groups. PaCO2 was greater in the face mask group than the laryngeal mask group at 3 minutes (54 +/- 11 mm Hg, 41 +/- 8 mm Hg, respectively) and 5 minutes (52 +/- 11 mm Hg, 43 +/- 15 mm Hg, respectively) after electrical stimulation (p<0.01). Mean blood pressure was higher than the corresponding preanesthesia value at 1 to 5 minutes after electrical stimulation in the face mask group and at 1 to 3 minutes after electrical stimulation in the laryngeal mask group. Mean seizure duration in the face mask group was significantly shorter than that in the laryngeal mask group (33 +/- 11 seconds, 42 +/- 10 seconds, respectively p<0.01). The change in PaCO2 was minor in the laryngeal mask group compared with the face mask group and seizure duration was longer in the laryngeal mask group. Laryngeal mask may be suitable for airway management during ECT anesthesia, especially when fitting a face mask is difficult.

Adult↗

Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function.

The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF + G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.

Adolescent↗

Antinociception with intrathecal alpha-methyl-5-hydroxytryptamine, a 5-hydroxytryptamine 2A/2C receptor agonist, in two rat models of sustained pain.

UNLABELLED: Type 2 serotonin (5-hydroxytryptamine [5-HT](2)) receptors in the spinal cord have been reported to mediate antinociception using pain threshold tests, but little is known about the actions of spinal 5-HT(2) receptors in sustained pain. In rats, we examined antinociceptive effects of the intrathecal administration of a 5-HT(2A/2C) receptor agonist, alpha-methyl-5-HT maleate (alpha-m-5-HT), using the formalin test and the chronic constriction injury (CCI) model. An intrathecal catheter was implanted for injection of drugs. In the formalin test, flinches were counted from Minute 1 to 2 and Minute 5 to 6 (Phase 1) and then for 1-min periods at 5-min intervals from 10 to 60 min (Phase 2). In rats with CCI, hind paw withdrawal latency after thermal stimulation was measured. In the formalin test, intrathecal administration of alpha-m-5-HT (1 to 100 microg) dose-dependently suppressed the number of flinches in both Phases 1 and 2. In the CCI model, intrathecally administered alpha-m-5-HT (10 to 100 microg) attenuated thermal hyperalgesia in a dose-dependent manner. These effects were reversed by intrathecal pretreatment with a 5-HT(2A/2C) antagonist, ketanserin (30 microg), or a muscarinic receptor antagonist, atropine (30 microg). These findings suggest that spinal 5-HT(2A/2C) receptors mediate antinociception in inflammatory pain and neuropathic pain, and the muscarinic receptors contribute to this action. IMPLICATIONS: Activation of spinal 5-hydroxytryptamine(2A/2C) receptors mediate antinociception in rat-sustained pain models such as inflammatory pain and neuropathic pain, and spinal muscarinic receptors are involved in this action.

Animals↗

Neurotrophic factors can partially reverse morphological changes induced by mepivacaine and bupivacaine in developing sensory neurons.

UNLABELLED: Both bupivacaine and mepivacaine induce morphological changes in growing neurons. We designed this study to investigate the role of some neurotrophic factors (NTFs) in supporting developing neurons exposed to the deleterious effects of these drugs. Dorsal root ganglia were isolated from chick embryos and exposed to either bupivacaine or mepivacaine. After 60 min of exposure, the culture media were replaced with fresh culture media free from local anesthetics. NTFs-brain-derived NTF, glial-derived NTF, or neurotrophin-3-were added to the replacement media, and the cells were examined up to 48 h after the washout. The growth cone collapse assay was applied by a quantitative method of assessment. When the replacement media were not supported by any NTF, the growth cone collapse values were significantly larger than the control values at 20 h after the washout of mepivacaine and 48 h after the washout of either bupivacaine or mepivacaine (P < 0.05). However, when any of the NTFs were used, the collapsing activity was significantly attenuated, and growth cone collapse values showed no statistically significant differences in comparison with the control values at these time points (P > 0.05). We conclude that several NTFs support the recovery of neurons after exposure to local anesthetics. The supporting effects of NTFs on the reversibility of mepivacaine-induced collapse tended to be more obvious than those seen after the bupivacaine washout. IMPLICATIONS: Three neurotrophic factors (NTFs) can partially support the reversibility of mepivacaine- and bupivacaine-induced growth cone collapse in growing primary cultured sensory neurons. The effect of NTFs is more apparent after mepivacaine than after bupivacaine washout.

Anesthetics, Local↗

A case of cerebral sinus thrombosis developed during a high-altitude expedition to Gasherbrum I.

We report a case of cerebral sinus thrombosis, which is a rare but serious complication that may develop during high-altitude climbing. A climber who reached the summit of Gasherbrum I (8068 m) suffered from motor weakness and gait disturbance as he descended from the peak. Within a few days, the symptoms progressed until he could not walk. Following a difficult and week-long rescue mission by his colleagues, he was hospitalized and diagnosed with thrombosis at the superior sagittal and right transverse sinuses. Climbers and rescuers should know the risk factors of this complication, such as hemoconcentration, procoagulability, and dehydration.

Adult↗

Successful transradial coronary angioplasty and stenting using a self-expandable RADIUS stent to the anomalous left main coronary artery.

Stenting of anomalous coronary artery is technically challenging both from the femoral and radial approaches because of difficulty in cannulating the artery by the guiding catheters with enough back-up support for delivering the stent. We report the first case in the literature of transradial coronary angioplasty and stenting to an anomalous left main coronary artery originating from the right sinus of Valsalva. Left Amplatz guidance from the radial approach provided an adequate platform to advance the stent using a dummy guidewire technique, and a self-expandable RADIUS stent was successfully deployed in a tortuous lesion of the anomalous artery.

Aged↗

[Feasibility of combination mapping utilizing a duo-decapolar electrode catheter and the CARTO system for incisional reentrant atrial tachycardia with cycle length alternation: a case report].

A 43-year-old woman had undergone patch closure operation for atrial septal defect 27 years ago. She was referred to our hospital for evaluation of frequent palpitations since 1 year ago. Electrophysiological study was performed with recording of the coronary sinus, His bundle, and low lateral right free wall electrography utilizing a steerable duo-decapolar electrode catheter(Livewire, Daig). Supraventricular tachycardia with cycle length alternation of 300 and 320 msec similar to atrial flutter was reproducibly provoked by burst pacing from the coronary sinus. During the supraventricular tachycardia, abnormal atrial potentials occurred in the low lateral right free wall region with very low amplitude and splitting potentials. The cycle length alternation of the supraventricular tachycardia depended on the occurrence of the splitting potentials, that is, the splitting potentials were present during the supraventricular tachycardia with a long cycle and the splitting potentials were absent during the supraventricular tachycardia with a short cycle. This phenomenon suggested that the splitting potentials resulted from 2:1 functional intra-atrial local conduction block. In addition, during sinus rhythm the abnormal electrograms revealed fractionated activity. Thus, these findings strongly imply that the supraventricular tachycardia is due to a macro-reentrant right atrial tachycardia utilizing an anatomical obstacle caused by the atrial septal defect operation as a central area, namely incisional reentrant atrial tachycardia. Three-dimensional electroanatomical mapping using the CARTO system(Biosense-Webster) was conducted to investigate whether the low lateral right free wall area possessed the critical isthmus essential to the reentry circuit. Electroanatomical mapping revealed that the very low amplitude potentials and the splitting potentials corresponded to the scars and the functional conduction block area detected by mapping using the multipolar catheter, respectively. According to the propagation mapping, the incisional reentrant atrial tachycardia slowly conducted the channel created by multiple neighboring scars clockwise and the alternation of the tachycardia cycle length was dependent on the development of the functional local intra-atrial conduction block within the channel. An approximately 1.5 cm successful linear lesion was created by radiofrequency catheter ablation to transect the isthmus based on the electroanatomical mapping findings. Afterwards, the incisional reentrant atrial tachycardia could not be induced by burst stimuli from the coronary sinus even under administration of isoproterenol. The use of three dimensional electroanatomical mapping(CARTO system) to evaluate the reentry circuit after the detection of abnormal potentials by using multipolar catheter in advance is a very useful method to determine optimal target site of ablation for a patient with incisional reentrant atrial tachycardia.

Adult↗

[The differential effects of isoproterenol on +dp/dt max and -dp/dt max under volatile anesthetics in rat].

BACKGROUND: The purpose of this study is to examine the effects of isoproterenol on +dp/dt max and -dp/dt max under volatile anesthetics in rat. METHODS: Firstly, under different halothane or isoflurane (0, 0.5 MAC, 1.0 MAC, 2.0 MAC) concentrations, hemodynamic parameters were recorded simultaneously. Secondly, under different halothane or isoflurane concentrations (0, 0.5 MAC, 1.0 MAC, 2.0 MAC), the inotropic response to isoproterenol was also studied with cumulative (0, 5, 50, 100, 500, 1000 pg) concentrations and hemodynamic parameters were simultaneously recorded. RESULTS: There were significant decreases in +dp/dt max and -dp/dt max in halothane and isoflurane treated rats. The decreases in +dp/dt max and -dp/dt max were greater in halothane treated rats than those in isoflurane treated rats (P < 0.05) under 2 MAC halothane. The responses of +dp/dt max and -dp/dt max to 500 and 1000 pg isoproterenol were significantly reduced by 2 MAC halothane compared with the control (P < 0.05). There were no significant changes in +dp/dt max and -dp/dt max by administration of isoproterenol under isoflurane anesthesia. CONCLUSIONS: Isoflurane has less effects on +dp/dt max and -dp/dt max, compared with halothane. It is possible that halothane, but not isoflurane, has some effects on the responsiveness to isoproterenol.

Anesthetics, Inhalation↗

[Blood-brain barrier and general anesthetics].

The transport of drugs into the brain is prevented in most cases by the presence of the blood brain barrier (BBB). Endothelial cells in the brain of vertebrates are fused together by tight junctions that eliminate the normal pathways of free diffusion existing in the capillary beds of organs other than the brain or spinal cord. Therefore, a molecule that has a molecular weight less than a 500 Dalton can cross the BBB in proportion to lipid solubility. Recent molecular biological studies have contributed to the isolation and functional analysis of transporter proteins at the BBB. There are three types of endogenous transport systems: carrier-mediated transporters, active efflux transporters such as P-glycoprotein, and receptor-mediated transcytosis systems. The structural and functional integrity of the BBB has appeared to be dramatically altered by various diseases of the CNS such as ischemia, anoxia and inflammation, resulting in cerebral edema and damage to the neurons. General anesthetic agents can alter the BBB function. For example, the degree of the BBB disruption was smaller during isoflurane anesthesia than during pentobarbital anesthesia. In this review, we focus on recent progress in the BBB research and functional modulation produced by general anesthetics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Lymphoid enhancer-binding factor-1 binds and activates the recombination-activating gene-2 promoter together with c-Myb and Pax-5 in immature B cells.

The recombination-activating gene (RAG)-1 and RAG-2 are expressed specifically in immature lymphoid cells undergoing the recombination of Ag receptor genes. We studied the regulation of murine RAG-2 promoter and revealed that -41/-17 RAG-2 promoter region, which was indispensable for the RAG-2 promoter activity in B cell lines, contained binding sites for lymphoid enhancer-binding factor-1 (LEF-1), c-Myb, and Pax-5. We showed that these three transcription factors bound the promoter region in vitro and in vivo. Cotransfection assays using a human embryonic kidney cell line (293T) showed that LEF-1, c-Myb, and Pax-5 cooperatively activated the RAG-2 promoter, via their synergistic DNA binding. We also showed that LEF-1, c-Myb, and Pax-5 physically interact in the cells. Finally, we demonstrated that a dominant-negative LEF-1 protein, which lacks the binding site for beta-catenin, suppressed the RAG-2 promoter activity as well as the endogenous RAG-2 expression in a pre-B cell line (18.81). These results suggest that LEF-1/beta-catenin complex regulates the RAG-2 promoter activation in concert with c-Myb and Pax-5 in immature B cells. The link between LEF-1/beta-catenin and Wnt signaling in B lineage cells will be discussed.

5' Untranslated Regions↗

The effect of Au injection on the ceruloplasmin, metallothionein and 8-hydroxydeoxyguanosine of rat serum, kidney and liver.

The present study was carried out to investigate the effect of gold (Au) injection on copper (Cu) and two types of ceruloplasmin (Cp), total Cp (ID1) and active Cp (ID2), metallothionein (MT) in the serum, kidney and liver, and 8-hydroxydeoxyguanosine (8-OHdG) in the rat kidney. The Cu contents in sera and kidneys of Au-injected rats were 1.7 and 5.5 times higher than those in sera and kidneys of control rats, respectively. The most of Cu in the sera of the control rats or Au-injected rats were observed in the Cp fractions from a Sephacryl S-200 column. The Cu concentration in the Cp fractions was increased by Au injection. Significant increases of ID1 and ID2 were found in the sera of the control rats and Au-injected rats, while there was no significant difference in those concentrations of livers or kidneys between the control rats and Au-injected rats. Our results indicated that the most of Cp existed as active ID1. The immunoreactivity of 8-OHdG was located in the cortex of the Au-injected rat. These results indicated that the oxidative DNA damage occurred in the renal cortex of the Au-injected rat and the localization of DNA damage did not coincide with that of Cu-MT. These findings suggest that the oxidative DNA damage in the kidneys of rats injected with Au is associated with Cu except Cu-MT.

8-Hydroxy-2'-Deoxyguanosine↗

Characterization of chromatin structure and enhancer elements for murine recombination activating gene-2.

Recombination-activating genes (RAGs) play a critical role in V(D)J recombination machinery and their expression is specifically regulated during lymphocyte ontogeny. To elucidate the molecular mechanisms regulating murine RAG-2 expression, we examined a chromatin structure of 25-kb DNA segment adjacent to murine RAG-2 by analyzing DNase I hypersensitive (HS) sites. In a RAG-2-expressing murine pre-B cell line, three lymphoid cell-specific HS sites (HS1, HS2, and HS3) were identified. Among these HS sites, one HS site (HS3) that locates in the RAG-2 promoter was associated only with RAG-2-expressing cell lines. Using the transient enhanced green fluorescence protein reporter gene assays, we identified two enhancer elements in the 5'-upstream region of RAG-2 that corresponded to HS1 and HS2. One of the enhancer elements (D3) exhibited enhancer activity only in the lymphoid cell lines. Analysis of the transgenic mice carrying the enhanced green fluorescence protein-reporter gene linked with D3 revealed that D3 activated the reporter gene-expression in the primary lymphoid tissues, but not in the secondary lymphoid tissues or nonlymphoid tissues. D3 was active in CD4(-)CD8(-), but not in CD4(+)CD8(+) or CD4(+)CD8(-) thymocytes in the thymus, and also active in B220(+)IgM(-), but not in B220(+)IgM(+), cells in the bone marrow. Finally, our data suggested that C/EBP may bind to the D3 enhancer and function as one of the transcription factor(s) responsible for the enhancer activity. These results show that the tissue- and stage-specific expression of murine RAG-2 is regulated by alteration of the chromatin structure as well as cis-regulatory enhancer elements.

3T3 Cells↗

Possible involvement of a muscarinic receptor in the anti-allodynic action of a 5-HT2 receptor agonist in rats with nerve ligation injury.

Intrathecal administration of 5-HT(2) receptor agonists produces an anti-allodynic effect in a rat model of neuropathic pain. Several non-serotonergic neurotransmitters have been implicated these anti-nociceptive effects. In the present study, intrathecal pre-treatment with the muscarinic receptor antagonist atropine (10 and 30 microg) and pirenzepine (10 microg) reversed the anti-allodynic effect of the 5-HT(2) receptor agonist alpha-methyl-5-hydroxytryptamine, unlike various other antagonists. Thus, muscarinic receptors may be involved in the anti-allodynic action of intrathecally injected 5-HT(2) receptor agonist.

Analgesics↗

Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice.

The involvement of glucocorticoid response in the hippocampal changes in aged SAMP8 mice after removal of their upper molar teeth (molarless condition) was examined using biochemical, morphological and behavioral techniques. Molarless mice showed plasma corticosterone levels to be significantly greater than those in molar-intact control mice. Pretreatment with metyrapone, which suppresses the stress-induced rise in plasma corticosterone levels, prevented the molarless condition-induced increase in plasma corticosterone levels, reduction in CA1 pyramidal neuron numbers, and impairment of spatial learning. The results suggest a link between the molarless condition and the glucocorticoid response, which may be involved in spatial learning deficits and hippocampal neuronal death in aged SAMP8 mice.

Aging↗