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Biomedical subjects

S Kashimoto

Publications and source records attributed to S Kashimoto.

At least 73 records · Page 4Linked to original sources

Combination effect of recombinant human interleukin 1 alpha with antitumor drugs on syngeneic tumors in mice.

To investigate the combination effects of recombinant human interleukin 1 alpha (rHu IL-1 alpha) and antitumor drugs, groups of 7 mice bearing syngeneic tumors (Meth A sarcoma in BALB/c mice and colon 26 adenocarcinoma in BALB/c x DBA/2 F1 mice) were treated i.v. with the antitumor drugs according to the early (once daily on days 1, 4, 7, 10, and 13) and/or late (once daily on days 7, 10, 13, 16, and 19) medication schedules in combination with rHu IL-1 alpha administered i.m. at various timings (1 day before, concurrently with, and 1 day after every drug administration). Inhibition rates of the antitumor drugs (mitomycin C, doxorubicin, cisplatin, cyclophosphamide, and 5-fluorouracil) for both the murine tumors were more or less raised by coadministration of rHu IL-1 alpha irrespective of medication schedules and combination timings. After both early and late treatments with the optimal combinations of rHu IL-1 alpha (0.1-3 micrograms/mouse) and cisplatin (2-4 mg/kg) and by the late treatment with the optimal combinations of rHu IL-1 alpha (0.3-3 micrograms/mouse) and carboplatin (32 mg/kg) or thiotepa (4 mg/kg), many mice were completely cured of colon 26 adenocarcinoma and survived for more than 90 days. Combined use of rHu IL-1 alpha and antitumor drugs seems to be beneficial in antitumor chemotherapy.

Adenocarcinoma↗

Protective effects of prostaglandin I2 analogues on CPK release in rat's heart-lung preparation.

The effects of prostaglandin I(2) analogues (PGI(2)-a: op-41483 and op-2507) on oxygen toxicity during hyperoxic perfusion were evaluated in an experiment on isolated rat heart lung preparation, with the release of creatine phosphokinase (CPK) in the perfusate blood. There were no significant differences in heart rate and right atrial pressure between PGI(2)-a treated and untreated hearts. The CPK release from the heart with oxygen was significantly higher than that of the air ( P < 0.001). However, the CPK release from the PGI(2)-a treated hearts was significantly less than that from the untreated hearts ( P < 0.05). These results indicate that PGI(2)-a may prevent cell damage which was induced by hyperoxia.

Journal Article↗

Functional and metabolic effects of propafenone in the rat heart-lung preparation.

The effects of propafenone on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Propafenone 0.3, 3 or 30 microg.ml(-1) was administered 5 min after the start of perfusion. Heart rate decreased in the 30 microg.ml(-1) group significantly following the drug administration. The highest dose of propafenone (30 microg.ml(-1)) reduced cardiac output significantly, and this dose was associated with a higher incidence of arrhythmias than the other groups. Although there were no significant differences in myocardial lactate and glycogen concentrations among groups, ATP content in the 30 microg.ml(-1) group was significantly less than that in the control group. As therapeutic plasma concentration of propafenone is about 0.6 (range 0.06 to 1.0) microg.ml(-1), 30 microg.ml(-1) is 50 times greater than its concentration. These results suggest that the negative inotropic and chronotropic effects of propafenone are almost same with those of lidocaine which we have previously reported.

Journal Article↗

[The effect of prostaglandin E1 (PGE1) on body temperature and on postoperative shivering under high dose epidural fentanyl].

Ninety-nine elective abdominal surgeries were performed under high dose epidural fentanyl anesthesia. PGE1 (0.02 microgram.kg-1.min-1 = 0.02 gamma) was administered to 34 patients (0.02 gamma group), and PGE1 (0.05 gamma) was administered to 16 patients (0.05 gamma group). PGE1 was not administered to 49 patients (control group). The effect of PGE1 on body temperature and on postoperative shivering was compared within three groups. In the 0.02 gamma group, the temperature of the fingertip was significantly higher and the rectum-fingertip temperature gradient was significantly lower than in the other groups. The forearm-fingertip temperature gradient was lower in the 0.02 gamma and 0.05 gamma groups than in the control group. The incidence of postanesthetic shivering was significantly lower in the 0.05 gamma group than in the other groups. These results suggest that; 1) PGE1 (0.02 gamma and 0.05 gamma groups) affects the peripheral blood flow and peripheral temperature, and 2) PGE1 (0.05 gamma group) significantly affects the incidence of postanesthetic shivering.

Abdomen↗

Anaesthetic management of dilated cardiomyopathy with severe ventricular dysrhythmias.

A 67-year-old man with dilated cardiomyopathy underwent subtotal gastrectomy. The risks due to anaesthesia and surgery were considered to be very high because of the severe dysrhythmias and renal dysfunction. Anaesthesia was induced with fentanyl and midazolam and maintained with additional fentanyl, midazolam, and 60% nitrous oxide. Dobutamine, dopamine, lignocaine and a temporary pacemaker were used to control cardiovascular responses during surgery. Mild hypotension and tachycardia occurred, but neither circulatory failure nor other major complications were observed during and after the operation.

Aged↗

The effects of ulinastatin on cardiac and hepatic energy metabolism in rats subjected to hypovolemic shock.

Ulinastatin is a trypsin inhibitor extracted from human urine. In this study the effects of ulinastatin on myocardial and hepatic tissue concentrations of creatine phosphate (CP), ATP, ADP, AMP, lactate, pyruvate, and glycogen have been investigated in rats which were in hemorrhagic shock state. Hypovolemia was induced by bleeding from the femoral artery, and systolic blood pressure was maintained 40 mmHg for 25 min, then ulinastatin 50,000 units.kg(-1) in saline or saline vehicle was intravenously administered. Thereafter the heart and liver were extirpated and frozen quickly with liquid nitrogen. The tissue concentrations of CP, ATP, ADP, AMP, lactate and glycogen were measured enzymatically. Systolic blood pressure elevated significantly after ulinastatin administration. The myocardial tissue CP level was higher in ulinastatin-treated group than that of control group, whereas no significant difference in energy charge between two groups. The hepatic tissue level of AMP, lactate and L/P ratio was lower in ulinastatin-treated group than that of control group, however, no significant difference was found in hepatic tissue level of ATP, ADP and energy charge. From these results it is concluded that ulinastatin can improve the energy metabolism of myocardium to some extent, but not of the liver in rats with hypovolemic shock.

Journal Article↗

Anesthetic influence on myocardial energy metabolism during hemorrhagic shock in rats.

Twenty-eight male Wistar rats were used to assess the influence of inhalation anesthetics on myocardial energy metabolism during hemorrhage. They were anesthetized with pentobarbital and divided into four groups: a control group and three others which received 1.2% halothane, 2.2% enflurane or 1.4% isoflurane, respectively. Following a 15-min stabilization period, blood was gradually withdrawn over a 5-min period from a femoral artery. Systolic blood pressure was maintained at 40 mmHg for 30 min. Immediately after hemorrhage, the heart was removed and myocardial metabolites (ATP, ADP, AMP, lactate and glycogen) were measured by the enzymatic methods. Although no significant differences could be detected in ADP, AMP and lactate among the groups, there were significant increases of ATP content in rats receiving halothane and isoflurane when compared with the controls. There were also differences in myocardial glycogen content between the control group and those receiving isoflurane with those receiving halothane or enflurane. These results suggest that halothane or isoflurane may be more desirable than enflurane for maintenance of anesthesia during hypovolemia.

Adenosine Triphosphate↗

Interaction between calcium channel blockers and volatile anaesthetics in the rat heart-lung preparation.

We have studied the effects of the calcium channel blockers verapamil, diltiazem and nifedipine and the volatile anaesthetics halothane, enflurane and isoflurane on myocardial metabolism after postischaemic reperfusion in the rat isolated heart-lung preparation. In the presence of the volatile anaesthetics, the preparations were perfused for 10 min, made globally ischaemic for 8 min, and then reperfused for 10 min. Each of the calcium blockers was administered 5 min before ischaemia. Three hearts in the halothane-verapamil group (n = 10) failed to recover from the ischaemia and the recovery time in the same group was significantly longer than in the enflurane-verapamil or isoflurane-verapamil groups. Although there was no significant difference in myocardial lactate concentrations among the groups, ATP and glycogen contents in the halothane-verapamil group were significantly less than those in the other groups. The results suggest that the combination of halothane and verapamil causes significant myocardial depression during recovery from ischaemia and subsequent metabolic deterioration.

Anesthetics↗

Functional and metabolic effects of bupivacaine and lignocaine in the rat heart-lung preparation.

We have examined the effects of bupivacaine and lignocaine on myocardial metabolism in the rat isolated heart-lung preparation. Bupivacaine 1, 5 or 25 micrograms ml-1 or lignocaine 4, 20 or 100 micrograms ml-1 was administered 5 min after the start of perfusion. Both bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 reduced heart rate significantly. Bupivacaine 25 micrograms ml-1 was associated with a higher incidence of arrhythmias than the other groups. Three hearts in the bupivacaine 25 micrograms ml-1 group (n = 8) and two hearts in the lignocaine 100 micrograms ml-1 group (n = 8) failed (zero cardiac output) at the end of the experiment. Although there were no significant differences in myocardial lactate and glycogen concentrations between groups, ATP content in the bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 groups was significantly less than that in the control group. The results suggest that myocardial depression and subsequent metabolic deterioration occurred with both the high doses of local anaesthetics; these findings do not account for the apparent increased cardiotoxicity of bupivacaine.

Adenosine Triphosphate↗

Effects of sevoflurane on myocardial metabolism during postischemic reperfusion in the rat.

In experiments on isolated rat heart lung preparation, the effects of sevoflurane on myocardial metabolism during postischemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10 min initially and made globally ischemic for 8 min. Afterwards, they were reperfused for 12 min. Sevoflurane was administered from 5 min after the start of perfusion to the end of reperfusion. There was no significant difference in myocardial lactate levels between the sevoflurane (S) and control groups. However, the myocardial ATP level in Group S was significantly higher than that in control (17.45 +/- 1.51 vs 15.50 +/- 0.87 : P < 0.01). The administration of sevoflurane to the isolated rat heart during pre- and post-ischemia enhanced metabolic recovery in the postischemic state.

Journal Article↗

Effects of naloxone on cardiac energy metabolism in hypovolemic shock in rats.

It has been reported that naloxone may be useful in the treatment of hypovolemic shock. However, the effects of naloxone on cardiac energy metabolism in hemorrhagic shock have not been investigated. The effects of naloxone on myocardial metabolism were evaluated in the rats which were bled to a systolic pressure of 40 mmHg and maintained at that pressure for 30 min. Naloxone (10 mg/kg) was administered intravenously 5 min before the heart was removed. Then the intramyocardial high energy phosphates, pyruvate, lactate, and glycogen were measured. Naloxone increased systolic blood pressure and decreased heart rate significantly. However, there were no significant differences in high energy phosphates, energy charge, pyruvate, lactate and glycogen between the control and naloxone groups. These data suggest that naloxone may have no direct effect on the cardiac energy metabolism in a 30-min hypovolemic shock.

Animals↗

In vitro and in vivo antibacterial activities of AT-4140, a new broad-spectrum quinolone.

AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5- dimethyl-1-piperazinyl)-4-oxoquinoline-3-carboxylic acid, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.1 to 0.78 micrograms/ml against gram-positive organisms, such as members of the genera Staphylococcus, Streptococcus, and Enterococcus, and 0.0125 to 1.56 micrograms/ml against gram-negative organisms, such as members of the family Enterobacteriaceae and the genera Pseudomonas, Branhamella, Campylobacter, Haemophilus, and Neisseria. Its MICs were 0.025 to 0.78 micrograms/ml against glucose nonfermenters, such as members of the genera Xanthomonas, Acinetobacter, Alcaligenes, Moraxella, Flavobacterium, and Brucella; 0.2 to 0.78 micrograms/ml against anaerobes, such as Clostridium perfringens and Bacteroides fragilis; 0.0125 to 0.05 micrograms/ml against Legionella spp.; 0.0125 to 0.2 micrograms/ml against Mycoplasma spp.; 0.031 to 0.063 micrograms/ml against Chlamydia spp.; and 0.1 to 0.3 micrograms/ml against Mycobacterium spp. The potencies of AT-4140 against gram-negative organisms were comparable to those of ciprofloxacin and higher than those of ofloxacin, enoxacin, and norfloxacin. The potencies of AT-4140 against gram-positive organisms, glucose nonfermenters, anaerobes, Mycoplasma spp., Chlamydia spp., and Mycobacterium spp. were generally higher than those of the quinolones with which AT-4140 was compared. AT-4140 showed good oral efficacy against systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa in mice. Its efficacy was better when a daily dose was given once than when it was given in two doses. Good efficacies of the orally administered drug were also observed in pulmonary, dermal, and urinary tract infection models in mice. The in vivo efficacies of AT-4140 were equal to or better than those of ciprofloxacin, ofloxacin, enoxacin, and norfloxacin.

Animals↗

[Effects of inhalation anesthetics on hepatic ATP and L/P ratio in the rat subjected to hemorrhagic shock].

Both anesthetics and hemorrhage may affect the hepatic energy metabolism. The effects of inhalation anesthetics (halothane, enflurane and isoflurane) on hepatic ATP level and L/P ratio were evaluated in rat under hemorrhagic shock. There was no significant difference in the hepatic ATP levels among 4 groups. However the L/P ratio in 3 inhalation anesthetic groups was significantly lower than that in control group. These results suggest that inhalation anesthetics may improve the hepatic energy metabolism during hemorrhagic shock.

Animals↗

[A case report of hypoxia in a child after renal transplantation].

A 4 year-old boy underwent renal transplantation and the kidney was given by his mother. Anesthesia was induced slowly with halothane and nitrous oxide in oxygen. The trachea was intubated with pancuronium and the anesthesia was switched to neurolept anesthesia. Blood, plasmanate and crystalloid were infused in order to increase the circulatory blood volume measuring the CVP before the kidney was transplanted because it was so large for the child that it could not be perfused adequately. The spontaneous breathing and soon the recovery followed immediately after the end of operation. However, the patient became hypoxic on the next day probably due to the aspiration of gastric juice. He recovered from hypoxia after 3 days since the aspiration pneumonia was not severe. When the adult kidney is transplanted into a very small child, gastric juice can easily be regurgitated because of the high intraabdominal pressure. Therefore, we must be careful when a child undergoes renal transplantation.

Anesthesia, General↗

[Anesthetic management in surgery of a descending aortic aneurysm in an eighteen-month-old boy].

Aortic aneurysm occurs rarely in childhood. Most aneurysms in children are associated with conditions such as Marfan's syndrome, coarctation of the aorta, Ehlers-Danlos syndrome and neurofibromatosis. We report a case of descending thoracic-abdominal aortic aneurysm in an eighteen month old boy with a mask-like face, ocular hypertelorism, blepharoptosis, a high arched palate and low set ears. He was scheduled for a bypass graft of the descending thoracic and abdominal aorta under partial cardiopulmonary bypass. High dose morphine anesthesia (2mg/kg) was employed and halothane was used to control the blood pressure. To our knowledge, anesthetic management of such an infant had not been reported. Therefore, we anesthetized this child according to anesthetic managements for adult cases considering carefully the boy's multiple anomalies. Anesthetic managements for the surgery of aortic aneurysms in childhood are discussed.

Anesthesia↗

Effects of volatile anesthetics on cardiac metabolism in the low-pressure perfused rat heart.

Effects of halothane, enflurane and isoflurane on the myocardial metabolism were studied in the rat heart-lung preparation. Hearts were perfused at a low perfusion pressure (SBP 50 mmHg, DBP 30 mmHg) with succinate or glutamate as substrates. Thirty minutes after the perfusion, intramyocardial ATP, pyruvate, lactate and glycogen were measured enzymatically. Although there was no significant difference in ATP levels of hearts with either substrate, and whether or not volatile anesthetics were present, 1% halothane and 1.5% isoflurane reduced the L/P ratio when succinate was substrate (24.46 +/- 4.81, 17.68 +/- 9.10 vs 39.82 +/- 10.83), and 2% enflurane decreased it when glutamate was substrate (22.25 +/- 10.99 vs 38.44 +/- 6.55). The glycogen levels in volatile anesthetics groups were lower than control when succinate was substrate. The improvement of energy demand-supply balance by inhalation anesthetics may be stronger than their inhibition of electron transport in mitochondria under certain ischemic conditions.

Journal Article↗

Augmented antitumor effect of recombinant human interleukin-1 alpha by indomethacin.

In murine syngeneic tumor models, the antitumor effect of recombinant human interleukin-1 alpha (rHu IL-1 alpha) was significantly augmented by oral coadministration of indomethacin (IND). The augmentation was more or less observed by various routes of rHu IL-1 alpha (i.m., i.v., and intratumoral routes), against various tumors (Meth A sarcoma, colon 26 adenocarcinoma, B16 melanoma, and Lewis lung carcinoma) and irrespective of administration timings (in early and late stages of tumor growth). This results suggests that prostaglandin E2 produced by host cells in response to rHu IL-1 alpha and/or by tumor mass might interfere with the antitumor activity of rHu IL-1 alpha and also that cyclooxygenase inhibitors such as IND might counteract such interference. In the combination of rHu IL-1 alpha with IND, its efficacious doses (5-50 micrograms/kg) against murine tumors were at least 300-3000 times lower than its median lethal dose (more than 15 mg/kg). In addition, IND partially prevented the loss of body weight attributed to rHu IL-1 alpha injections at relatively high doses. Combined use of rHu IL-1 alpha with IND seems to be desirable from both therapeutic and toxicological viewpoints.

Adenocarcinoma↗