Biomedical subjects

S Dohi

Publications and source records attributed to S Dohi.

At least 91 records · Page 5Linked to original sources

PubMed1997

Increased activity of small GTP-binding protein-dependent phospholipase D during differentiation in human promyelocytic leukemic HL60 cells.

In response to dibutyryl cyclic AMP (dbcAMP) and all-trans retinoic acid, human promyelocytic leukemic HL60 cells differentiate into granulocyte-like cells. In cell lysate and in vitro reconstitution system, phospholipase D (PLD) activity in response to guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was up-regulated by dbcAMP or all-trans retinoic acid treatment. In the present study, the mechanism(s) for increased PLD activity during differentiation was examined. Western blot analysis revealed that the contents of ADP-ribosylation factor, Rac2, and Cdc42Hs but not RhoA and Rac1 in the cytosolic fraction were elevated during differentiation. However, the cytosolic fraction from undifferentiated cells was almost equally potent as the cytosolic fraction from differentiated cells in the ability to stimulate membrane PLD activity. It was shown that the GTPgammaS-dependent PLD activity in membranes from differentiated cells was much higher than that in membranes from undifferentiated cells, suggesting that the increased PLD activity during differentiation was due to alterations in some membrane component(s). Clostridium botulinum ADP-ribosyltransferase C3 and C. difficile toxin B, which are known as inhibitors of RhoA and Rho family proteins, respectively, effectively suppressed PLD activity in membranes from differentiated cells. In fact, the amount of membrane-associated RhoA was increased during differentiation. Furthermore, the extent of GTPgammaS-dependent PLD activity partially purified from membranes from differentiated cells was greater than that from membranes from undifferentiated cells in the presence of recombinant ADP-ribosylation factor 1. The PLD (hPLD1) mRNA level was observed to be up-regulated during differentiation, as inferred by reverse transcription-polymerase chain reaction. Our results suggest the possibility that the increased Rho proteins in membranes and the changed level of PLD itself may be, at least in part, responsible for the increase in GTPgammaS-dependent PLD activity during granulocytic differentiation of HL60 cells.

ADP-Ribosylation Factors↗

PubMed1997

New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human skin grafts containing intraepidermal neoplasms.

Engraftment of normal or lesional human skin onto nude or SCID (severe combined immunodeficiency) mice has been used as an in vivo experimental model. However, this model has some limitations, such as shrinkage and loss of the grafted skin over time. To improve the experimental model, we have produced two new SCID-lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige-scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal neoplastic lesions such as Bowen's disease were grafted onto the back of the mice of these strains. The rate of reduction in the size of the grafts was lower on nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic cells in the grafts were higher in nude-scid mice than in SCID and beige-scid mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells of Bowen's disease grafted onto a beige-scid mouse proliferated and invaded the dermis during 233 days of observation, confirming the progression to invasive squamous cell carcinoma from carcinoma in situ. The present study revealed that nude-scid and beige-scide mice newly produced by us provide a very useful in vivo experimental model for the investigation of carcinogenesis and tumor progression in human skin.

Animals↗

PubMed1997

The effects of bupivacaine and ropivacaine on baroreflex sensitivity with or without respiratory acidosis and alkalosis in rats.

Systemic toxicity of local anesthetics causes cardiac and central nervous system (CNS) depression that could be enhanced in the presence of respiratory acidosis. We examined a potential suppression of baroreflex function with bupivacaine and ropivacaine during hypercapnic acidosis or hypocapnic alkalosis. Baroreflex sensitivity (BRS) was randomly tested in rats with one of 13 conditions during intravenous administration of saline (control), bupivacaine 1, 2, or 3 mg/kg, or ropivacaine 2, 4, or 6 mg/kg. The effects of bupivacaine (3 mg/kg) or ropivacaine (6 mg/kg) on BRS were also examined during hypercapnic acidosis or hypocapnic alkalosis. The BRS was assessed using a value of delta heart rate/ delta mean arterial pressure after infusion of phenylephrine (3 micrograms/kg). Both bupivacaine and ropivacaine (at the largest dose) significantly suppressed BRS. Acute respiratory acidosis (pHa 7.24 +/- 0.04, Paco2 63 +/- 4 mm Hg) enhanced BRS. The BRS enhanced during acidosis was also suppressed with bupivacaine and ropivacaine, but less so than in the absence of acidosis. The presence of hypocapnic alkalosis (pHa 7.55 +/- 0.03, Paco2 25 +/- 2 mm Hg) did not affect BRS and reversed BRS suppression caused by both drugs. Thus, bupivacaine and ropivacaine affect neuronal control mechanisms for maintaining cardiovascular stability, and acute changes of respiration could significantly modify such suppression.

Acidosis, Respiratory↗

PubMed1997

The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients.

Lidocaine and tetracaine suppress superoxide anion (O2-) generation of neutrophils. We examined the effects of eight local anesthetics on O2- generation in human neutrophils and searched for a potential relationship between the biological activities and the physicochemical properties of presently available eight local anesthetics. Human neutrophils incubated with local anesthetic and a Cypridina luciferin analog as a O2(-)-specific chemiluminescence probe were stimulated by phorbol ester. The chemiluminescence development based on O2- generation was monitored by a luminometer. All of the tested local anesthetics suppressed O2- generation in a concentration-dependent manner. The concentration of each of eight local anesthetics that produced 50% inhibition of peak chemiluminescence (IC50) had a rank order of dibucaine < tetracaine < bupivacaine < ropivacaine < procaine < mepivacaine < lidocaine = prilocaine. A linear relationship was obtained between IC50 values and the values of logarithm of partition coefficient (log P) of eight local anesthetics; log (IC50 in molarity) = -1.252 - 0.514 x log P, r2 = 0.891, P < 0.001. Unlike with staurosporine, which inhibits protein kinase C (PKC), no effect was observed on the O2- generation in the presence of tetrodotoxin (TTX), veratridine (VTD), or amiloride. These results suggest that the inhibitory effects of local anesthetics on O2- generation of neutrophils are predicted by physicochemical properties of the drugs, especially partition coefficients.

Amiloride↗

PubMed1997

The effects of topical and intravenous ropivacaine on canine pial microcirculation.

To assess the direct cerebrovascular effects of ropivacaine, we studied pharmacological responses to its topical and intravenous (IV) administration on vasomotor tone of pial vessels in in vivo experiments using a parietal cranial window in 24 dogs anesthetized with pentobarbital. We directly measured the diameters of pial arteries and veins after the administration of five different concentrations of ropivacaine solution (10(-7) to 10(-3) mol/L) randomly given into the window (n = 10). In six dogs, after pretreating the pial vessels with yohimbine (10(-5) mol/L), the inhibitory action of yohimbine was examined after the application of ropivacaine (10(-3) mol/L). The effects of IV ropivacaine (1 and 4 mg/kg) were also evaluated in the remaining eight dogs. Ropivacaine produced significant constriction of the pial arteries in a concentration-dependent manner (10(-7) to 10(-3) mol/L, P < 0.05) and only exerted a constrictive action on small veins (P < 0.05) at 10(-3) mol/L. Yohimbine had no effect on ropivacaine-induced constriction of pial vessels. IV ropivacaine, 4 mg/kg but not 1 mg/kg, caused pial vascular constriction (large arteries P < 0.005, small arteries P < 0.0001, large veins P < 0.01, small veins P < 0.005) associated with decrease in heart rate (P < 0.001). The results indicate that topical application of ropivacaine constricts pial arterial vessels in a concentration-dependent manner. A large dose of IV ropivacaine produced pial vasoconstriction associated with a decrease in heart rate and no decrease in mean arterial blood pressure. These effects do not appear to be mediated via the mechanism that depends on the activation of alpha2-adrenoceptors. We conclude that ropivacaine in high concentrations could, perhaps directly, cause significant constriction of the central nervous system vasculature.

Administration, Topical↗

PubMed1997

Spinal conduction block by intrathecal ketamine in dogs.

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

Anesthesia, Spinal↗

PubMed1997

Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique.

BACKGROUND: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. METHODS: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. RESULTS: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. CONCLUSIONS: The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.

Amides↗

PubMed1997

Effects of blood glucose changes and physostigmine on anesthetic requirements of halothane in rats.

BACKGROUND: Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. METHODS: In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). RESULTS: In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. CONCLUSIONS: Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.

Anesthetics, Inhalation↗

PubMed1997

[The differences of the cerebral and spinal vessels in sensitivity to PaCO2 and vasoconstrictors].

We investigated the differences in the response to arterial CO2 tension and vasoconstrictors between the cerebral and spinal vasculatures using cranial and spinal window technique which provided the direct observation of pial vessels. Pentobarbital anesthetized dogs (n = 18) (CO2 tension; n = 6 and vasoconstrictor; n = 12) were instrumented for measurement of pial vessel diameters by intravital microscopy in the cranial and spinal window preparation simultaneously. We achieved hypocarbia (20-25 mmHg) followed by adjusting CO2 levels for normocarbia (35-40 mmHg) and for hypercarbia (55-60 mmHg) using CO2 gas addition. After obtaining the desired PaCO2, the measurements were made. In the next experiment, we administered 2 different concentrations of epinephrine or phenylephrine solutions (1:2 x 10(6), 1:2 x 10(5)) through the window, and the measurement was made sequentially. The response of cerebral and spinal vasculature to change in PaCO2 was almost similar. Topical application of both drugs produced a significant constriction of spinal pial arterioles compared with the cerebral ones, while epinephrine but not phenylephrine constricted cerebral pial venules compared with spinal ones. These results suggest that the responses to vasoconstrictor of cerebral and spinal pial vessels are not similar, and high sensitivity of spinal arterioles to vasoconstrictors may possibly contribute to a risk of ischemic damage of the spinal cord.

Animals↗

PubMed1997

[Usefulness of alpha 2-adrenoceptor agonists and practical problems associated with their use in clinical anesthesia--II. Effects in regional anesthesia and analgesic effects for pain relief].

In the second part of this review, we summarized the effects of alpha 2-adrenoceptor agonists (clonidine and dexamedetomidine) in regional anesthesia and pain control, and evaluated their usefulness as anesthetic adjuvants and analgesics in the clinical settings. In addition, we referred to practical problems associated with their use.

Adjuvants, Anesthesia↗

PubMed1997

[A case of leukocytosis after massive blood transfusion for postpartum hemorrhagic shock].

We experienced the perioperative management of a hemorrhagic shock associated with postpartum uterine rupture. After the emergency abdominal total hysterectomy, massive blood transfusion was required to maintain the hemodynamics and the laparotomy for hemostasis was performed on the 1st, 2nd and 7th ICU day. Total amount of transfused blood products was 37,000 ml during one week. The patient immediately developed DIC and acute renal failure. Laboratory data showed increased leukocyte count (the peak value was 56,100 microliters-1 on the 12th ICU day), and neutrophilic fraction was more than 90% of leucocyte. After the decrease in CRP, the decrease in total bilirubin concentration was delayed. There were no other signs of infection and no remarkable change in MOF score. There was a discrepancy between this leukocytosis and the severity of organ dysfunction, and the cause of the leukocytosis was unknown.

Female↗

PubMed1997

[Bronchospasm due to anaphylactic reaction to Hydroxyethyl starch (HESPANDER)].

A 14-year-old male without any history of allergic disorders developed severe bronchospasm with skin rash 15 min. after the administration of hydroxyethyl starch (HES) during thoratic epidural anesthesia supplemented with N2O-sevoflurane-O2 anesthesia. Aminophylline, hydrocortisone, and epinephrine were administered. These treatments were effective, and the airway pressure was restored to normal ranges within 3 hrs. After the operation, the patient was extubated, because the results of the arterial blood gas examinations recovered to normal ranges. Plasma histamine and complement levels were almost within normal limits, but IgE levels were approximately 5 times higher than normal. Subsequent immediate skin test with hydroxyethyl starch showed an immunologically positive response. These results demonstrate evidence that an anaphylactic reactions could occur just after the start of HES infusion. Severe adverse reactions to HES are very rare, but it is important to keep the possibility always in mind.

Adolescent↗

PubMed1997

[Changes in alpha 2-adrenoceptor binding nature in guinea-pig brain following the development of morphine dependence].

We examined the effect of morphine dependence on alpha 2-adrenoceptors in guinea-pig brain. We also studied the influence of clonidine on the naloxone-induced withdrawal signs. 1. Guinea-pigs were implanted subcutaneously with MS contin (300 mg.kg-1). Two days after implantation, the binding of 3H-UK14304 (alpha 2 selective ligand) to brain membranes prepared from morphine dependent and control animals was determined. Scatchard plot of the saturation binding data revealed an increase in Bmax values and no change in the Kd values from dependent animals. These results indicate that brain alpha 2-adrenoceptors are up-regulated in morphine dependent guinea pigs. 2. Subcutaneous injection of naloxone on the 2 nd day after implantation caused characteristic withdrawal symptoms. Clonidine has been shown to reduce some opiate withdrawal signs in morphine-dependent animals.

Adrenergic alpha-Agonists↗

PubMed1997

[Changes in opioid receptor binding nature in rat brain and spinal cord following formalin or carrageenan-induced nociception].

Previous reports demonstrated the regulation of opioid and their receptor in nociception, but it is not clear how nociceptive activation may alter opioid receptor binding nature. We determined the change of mu, delta and kappa opioid receptor types in brain and spinal cord homogenates obtained from animal models receiving nociceptive treatment. 1) Rats received a subcutaneous injection of formalin and carrageenan into planter aspect of a hindpaw. These agent-injected animals were observed for appearance of pain-related behavior (guarding of the treated paw) within 2-3 hour after treatment. Following these pain behavior, rats were decapitated and brain and spinal cord were removed rapidly. 2) The binding of 3H-DAGO (mu agonist), 3H-DPDPE (delta agonist) and 3H-EKC (kappa agonist) to brain and spinal cord membranes prepared from nociceptive treatment and control rats was determined. Using these tracer 3H-opioid ligands, we failed to see any change in the total number of opioid binding sites (Bmax values) or the affinity constant (Kd values) for binding in whole brain and spinal cord. These results indicate that in these animal models which use experimentally induced inflammation to stimulate a condition of nociception, there appears to be no alteration in the levels of mu, delta or kappa binding sites.

Animals↗

PubMed1997

[Effects of nicorandil on regional cerebral oxygen saturation].

Nicorandil is usually considered to be a potent antianginal agent characterized as a potassium channel opener. It has been suggested that it may exert similar action on cerebral vessels. We administered nicorandil to surgical patients under general anesthesia. While the regional cerebral oxygen saturation (rSO2) and blood volume index (BVI) were determined continuously, each patient received the drug at dose of 0.08 mg.kg-1.h-1 initially, and after 15 minutes, the dose was increased by 0.08 mg.kg-1.h-1 at a time. This was repeated until the dose reached 0.40 mg.kg-1.h-1. At every dose level, rSO2 and BVI were determined, and the dose-response relationship was obtained. We found that nicorandil also produces cerebral arterial dilation under clinical conditions.

Adult↗

PubMed1997

[Hemodynamic effects of continuous epidural infusion with local anesthetics].

Epidural blockade with local anesthetic may cause hypotension resulting from sympathetic block and/or systemic effect produced by absorbed local anesthetic through epidural blood vessels. In the present study, we compared the hemodynamic effects of saline 0.5 ml.h-1, lidocaine 0.5 ml.h-1, bupivacaine 0.5 ml.h-1, lidocaine 2 ml.h-1, and bupivacaine 2 ml.h-1, which were given epidurally combined with morphine. There was not significant difference in hemodynamics among 5 groups. Continuous epidural infusion with a small dose of local anesthetic agent combined with morphine is unlikely to induce apparent hemodynamic effects during postoperative period.

Adult↗

PubMed1996

[Intraoperative acute myocardial infarction during total gastrectomy under general anesthesia combined with thoracic epidural anesthesia].

A 61-year-old, 54-kg man with gastric cancer was scheduled for total gastrectomy under general anesthesia combined with thoracic epidural anesthesia. Approximately 20 minutes after the start of the operation, the patient developed sudden hypotension and ventricular fibrillation. The cardiac rhythm returned to normal after 38 minutes of cardiopulmonary resuscitation. The operation was discontinued and the patient was transferred to an intensive care unit. A 12-lead electrocardiogram (ECG) revealed complete right bundle branch block and elevation of the ST-segment from leads II, III, aVF, V1, and V2 which indicated an inferior myocardial infarction. Laboratory data showed elevated levels of enzymes such as glutamic oxaloacetic transaminase (495 IU.l-1), lactic dehydrogenase (1781 IU.l-1), and creatine kinase-MB (112 IU.l-1). The mildly elevated levels of the enzymes decreased around 10 hours after the termination of the operation, but they increased markedly again without any change in ECG on the second postoperative day. Elevation in serum myoglobin and glutamic pyruvic transaminase and decline in arterial ketone body ratio were also detected. Furthermore, renal failure developed with increase in blood urea nitrogen and creatinine. Because of hepatic failure and renal failure which might have been caused by rhabdomyolysis, the patient needed inotropic support with dopamine, dobutamine, and epinephrine to maintain the circulation. The patient died of reinfarction of the 20th postoperative day despite intensive care such as intraaortic balloon pumping, hemodiafiltration, and continuous intravenous infusion of prostaglandin E1.

Acute Kidney Injury↗

PubMed1996

[Perioperative managements of a mentally retarded child with obstructive sleep apnea syndrome for adeno-tonsillectomy].

We describe a mentally retarded child with obstructive sleep apnea syndrome (OSAS) in whom it was difficult to maintain upper airway in the perioperative period. The child underwent awake intubation, because the preanesthetic evaluation of the airway with a direct fiberoptic visualization revealed a very narrow airway. Also we considered that if we used an anesthetic agent, a perioperative airway management would be very troublesome. Postoperatively we continuously monitored for apnea and arrhythmias. When the child was sleeping, we found frequently that her thoratic movements were getting weak and percutaneous oxygen saturation went down to about 70 percent. The preoperative direct fiberoptic visualization of the upper airway is effective for the evaluation of the degree of airway obstruction in this child. We also recommend the continuous intensive postoperative monitorings including pulse oximetry, ECG, and apnea monitor which are very important to avoid life-threatening complications such as upper airway obstruction and serious arrhythmias in patients with obstructive sleep apnea syndrome.

Adenoidectomy↗