Sympathetic modulation of cutaneous polymodal receptors in chronically inflamed and diabetic rats.
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Animals↗
Biomedical subjects
T Kumazawa
Publications and source records attributed to T Kumazawa.
Temperatures measured by a deep body thermometer (Coretemp) compared with tissue temperatures measured at various depths using needles placed into the sole of the foot.
Continuous monitoring of body temperature during anaesthesia is a widely accepted clinical practice for which a variety of techniques are used. In this study, the accuracy of the deep body thermometer (Coretemp) was compared with temperatures measured by needle thermocouples. With IRB approval and informed consent, seven ASA physical status I and II patients undergoing otolaryngeal surgery were studied. General anaesthesia and neuromuscular blockade were induced with thiamylal and vecuronium. Anaesthesia was maintained with isoflurane at an end-tidal concentration of 1.0-2.0% and 66% nitrous oxide in oxygen. After induction of general anaesthesia, subcutaneous temperature was measured at the sole of the left foot using a Coretemp. Additionally 8-, 18-, and 38-mm-long needle thermocouples were inserted into the the sole of the left foot close to Coretemp and skin-surface temperature was also recorded adjacent to the needles. The Coretemp measurement (Tc) correlated best with 18-mm-deep needle temperature (r2 = 0.87). There was also a good correlation between Tc and 38-mm-deep needle temperature (r2 = 0.83). Skin and 8-mm-deep needle temperatures correlated poorly or only moderately with Tc (r2 = 0.67, 0.75, respectively). These results indicate that temperatures measured by Coretemp well reflect the temperatures at a depth of 18 mm or more from the skin into the foot.
Anesthesia, General↗
Characterization of the purified cytosolic thymidine kinase from murine ehrlich ascites tumor: interconversion of two different relative molecular weight forms.
Cytosolic thymidine kinase was purified 18,000-fold of the homogenate from murine Ehrlich ascites tumor, using the [p-aminophenyl 3' -dTMP]-CH-Sepharose affinity column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single protein band of molecular weight 26,000. Two different forms, relative molecular weight 50,000 and 70,000, were found by gel filtration, depending on the existence of dithiothreitol, ATP and other nucleotides. These agents also stabilize and stimulate the enzyme activity. The existence of two forms was also manifested by DEAE-Sephacel column chromatography, where the 50,000 form was eluted by 50 mM NaCl and the 70,000 form by 400 mM NaCl.
Adenosine Triphosphate↗
EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat.
1. Our previous studies, in which we used in vitro canine testispermatic nerve preparations, showed that prostaglandin E2 (PGE2) augments both bradykinin (BK)- and heat-induced discharges of polymodal receptors. However, the PGE2 concentration required to augment the BK responses were 100 times lower than those necessary for the heat responses, suggesting that different receptors are involved in these phenomena. We studied which receptors for E series of prostaglandins (EP receptors) were responsible, using the antagonist and agonists for three subtypes of EP receptors. 2. PGE2-induced augmentation of the BK responses was unaffected when treated with an antagonist for the EP1 receptor, AH6809. 3. An agonist for the EP3 receptor, M&B28767, at > or = 10 nM, significantly augmented the BK responses in a concentration-dependent manner that mimics the PGE2-induced effect. An agonist for the EP1 receptor, 17-phenyl trinor PGE2 (17-phen PGE2), at the high concentrations of 0.1 and 1 microM, augmented the BK responses in two and four of nine cases tested, respectively. However, this augmentation was not suppressed by the antagonist for the EP1 receptor, AH6809. In addition, an agonist for the EP2 receptor, butaprost, did not affect the BK responses even when applied at 10 microM. 4. In contrast, butaprost at > or = 10 nM significantly augmented the heat responses in a concentration-dependent manner. M&B28767 and 17-phen PGE2, respectively, augmented the heat responses at higher concentrations of 100 nM and 1 microM. 5. These results indicate that the EP3 and EP2 receptor subtypes are differentially implicated in the respective PGE2-induced augmentation of BK responses and heat responses of polymodal receptors.
Alprostadil↗
H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro.
1. We examined excitation and the facilitatory effect on the heat responses induced by histamine in visceral polymodal receptors with the use of the canine testis-spermatic nerve preparation in vitro. 2. The proportion of units that showed excitation (> 10 impulses 1 min after application of histamine was initiated) increased roughly with higher concentrations of histamine: 7% at 1 microM, 26% at 10 microM, 79% at 100 microM, and 61% at 1,000 microM. The discharge rate also increased with the concentration. 3. Histamine (100 and 1,000 microM) responses > 0.5 imp/s were observed only in units with conduction velocities (CVs) of < or = 10 m/s, but not in those with CVs faster than 10 m/s. On average, histamine-induced discharges were significantly greater in units with CVs of < or = 10 m/s at all concentrations > or = 10 microM. Thus units studied in this experiment were empirically divided into slow-CV (< or = m/s) and fast-CV (> 10 m/s) groups. 4. Histamine significantly facilitated the heat responses of the slow-CV group from 10 microM, and also facilitated the fast-CV group from 100 microM. This sensitizing effect was observed irrespective of the precedent histamine-induced excitation. The magnitude of sensitization tended to increase with an increase in histamine concentration. 5. For studying the histamine receptor subtype involved in excitation and facilitation, we used D-chlorpheniramine maleate (5 microM) (an H1 receptor antagonist), famotidine (20 microM) (an H2 receptor antagonist), and thioperamide maleate (20 microM) (an H3 receptor antagonist). The magnitude of histamine-induced excitation of the slow-CV group was significantly suppressed by the H1 receptor antagonist but not by other antagonists. 6. The facilitatory effect of histamine on the heat response was also suppressed by the H1 receptor antagonist in both slow- and fast-CV groups. 7. These results strongly suggested that both excitation and facilitation of the heat response induced by histamine are mediated through the H1 receptor.
Animals↗
Inhibitors of acyl-CoA: cholesterol acyltransferase. II. Preparation and hypocholesterolemic activity of optically active dibenz[b,e]oxepin-11-carboxanilides.
In a previous paper, we reported a novel inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), 2-bromo-N-(2,6-diisopropylphenyl)-6,11- dihydrodibenz[b,e]oxepin-11-carboxamide (1). In this work, we prepared both enantiomers and tested them for ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters in vivo. The precursor carboxylic acid 4 was optically resolved with cinchonidine. The obtained (-)- and (+)-4 were converted to (-)- and (+)-1 without racemization, respectively. The enantiomer (-)-1 showed potent ACAT inhibitory activity in vitro with an IC50 value of 8 nM and was approximately 10-fold more active than (+)-1. Furthermore, (-)-1 showed strong hypocholesterolemic activity in vivo, whereas (+)-1 was inactive. A molecular modeling study showed that the difference of ACAT inhibitory activity between the enantiomers was derived from the spatial alignment of the bromine. Compound (-)-1 was selected for further evaluation as KW-3033.
Animals↗
[Intraoperative TEE revealed the mitral valve vegetation and the operation was cancelled].
Intraoperative transesophageal echocardiography (TEE) was performed on a 53-yr-old man scheduled for the venous graft in the left leg under general anesthesia. The TEE revealed the severe mitral valve vegetation and because of the finding, the operation was cancelled. Preoperative transthoracic echocardiography showed mitral valve regurgitation only, and not mitral valve vegetation. TEE was useful not only in assessing global and regional cardiac function, but also in visualizing anatomic abnormalities of the heart and their influence on cardiac performance.
Acute Disease↗
[Effects of amrinon and prostaglandin E1 on intraoperative central and peripheral temperatures during peripheral arterial surgery].
Effects of amrinon (AM) and prostaglandin E1 (PG) on body temperatures during surgery under general anesthesia were studied. Thirty-nine elective peripheral arterial surgery patients were assigned to one of three groups. All groups received dopamine (DOA) 3 micrograms.kg-1.min-1 after intubation and ten patients receiving only DOA served as a control group. Fifteen patients who received AM 1 microgram.kg-1 followed by AM 5 micrograms.kg-1.min-1 were assigned as an AM group. Fourteen patients who received PG 0.02 micrograms.kg-1.min-1 were defined as a PG group. Rectal and fingertip temperatures were monitored continuously during surgery. Fingertip temperatures in both AM and PG groups were significantly higher than those in the control group 120 minutes after the administration of drugs. On the other hand, rectal temperatures in all groups did not differ significantly throughout the study. The rectum-fingertip temperature gradient was lower in both AM and PG group than in the control group. These results suggest that bolus injection of AM 1 microgram.kg-1 followed by AM 5 micrograms.kg-1.min-1 and PG 0.02 micrograms.kg-1.min-1 may be effective for maintaining central and peripheral temperatures during surgery under general anesthesia.
Aged↗
[A case of coronary artery spasm during burr hole opening for craniotomy].
We report a rare case of coronary artery spasm during burr hole opening for craniotomy in a patient with no past history of coronary artery disease. A 52-year-old man was scheduled for the removal of the brain tumor under general anesthesia. Anesthesia was induced with fentanyl, thiamylal, and vecuronium, and maintained with sevoflurane plus nitrous oxide in oxygen. When burr holes were made for the craniotomy, the heart rate decreased suddenly and the ECG in lead II demonstrated the elevation of the ST segment (0.3mV). After about 1 min, the ST segment elevation returned to normal without any treatment. The dura mater was rather tense with inspection. Despite many reported cases of coronary artery spasm during general anesthesia, coronary artery spasm during burr hole opening for craniotomy has not been reported. In the present case, since the heart rate decreased and the elevation of the ST segment occurred at the time of the burr hole opening for craniotomy, the activated vagal tone reflex induced by the stimulation of the dura mater seemed to have caused the coronary artery spasm.
Anesthesia, General↗
Gas chromatography with surface ionization detection: a highly sensitive method for determining underivatized codeine and dihydrocodeine in body fluids.
Underivatized codeine and dihydrocodeine in human plasma and urine have been determined with a high degree of accuracy by capillary gas chromatography (GC) with surface ionization detection (SID). The drugs were extracted with the aid of Sep-Pak C18 cartridges. Recovery of both drugs was > or = 90%. The calibration curves obtained with dimemorfan as an internal standard showed linearity in the range 4.5-72.3 and 3.0-75.5 ng/ml of plasma for codeine and dihydrocodeine, respectively. The detection limit was about 100 pg on column (2.5 ng/ml sample). Codeine was determined quantitatively in plasma and urine obtained from a volunteer who had received 10 mg codeine phosphate orally 3 h before the sampling: the levels were found to be 14.1 and 142 ng/ml, respectively. The present GC-SID method has been compared carefully with GC-NPD (nitrogen-phosphorus detection) using the same extracts; the sensitivity of GC-SID was more than ten times greater than that of GC-NPD, with background noise correspondingly lower.
Adult↗
(E)-4-(2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy)butyric acid derivatives: a new class of steroid 5 alpha-reductase inhibitors in the rat prostate. 1.
A series of (E)-4-(2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy)butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyl or benzyl substituent of proper size at position 1 of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2- butenyl]-amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).
5-alpha Reductase Inhibitors↗
Rapid extraction and capillary gas chromatography for diazine herbicides in human body fluids.
A simple and rapid method for the extraction of four diazine herbicides (terbacil, bromacil, norflurazon and PAC) from human whole blood, plasma and urine with use of Bond Elut C18 cartridges is presented. Whole blood, plasma and urine samples containing the herbicides, after mixing with distilled water, were loaded on Bond Elut C18 cartridges and the herbicides were eluted with chloroform/methanol (9:1). They were detected by capillary gas chromatography with flame ionization detection (FID) with splitless injection. Separation of the four diazine herbicides from each other and from impurities was generally satisfactory with the use of an intermediately polar DB-17 capillary column. The recovery of all compounds, which had been added to whole blood, plasma and urine, was > 89%. The calibration curve for the herbicides, which has been added to whole blood, plasma and urine, showed linearity in the range 1.6-100 ng on column. Their detection limits were 1.2-1.4 ng on column for whole blood and plasma, and 1.1-1.2 ng on column for urine.
Bromouracil↗
Levels of pyrroloquinoline quinone in various foods.
The levels of free pyrroloquinoline quinone (PQQ) in various foods were examined by the use of gas chromatography-mass spectrometry. PQQ was extracted from the samples, after addition of [U-13C]PQQ as internal standard, with n-butanol and Sep-Pak C18 cartridges. After derivatization of PQQ with phenyltrimethylammonium hydroxide, molecular peaks at m/z 448 and 462 were used for detection of PQQ and [U-13C]PQQ respectively, by selected ion monitoring. Free PQQ could be detected in every sample in the range 3.7-61 ng/g or ng/ml. Since its levels in human tissues and body fluids are 5-10 times lower than those found in foods, it is probable that PQQ existing in human tissues is derived, at least partly, from the diet.
Coenzymes↗
A simple analysis of 5 thinner components in human body fluids by headspace solid-phase microextraction (SPME).
A simple method for the extraction of 5 thinner components from human whole blood and urine, using the headspace solid-phase microextraction (SPME) method is presented. After heating a vial containing the samples with 5 compounds (toluene, benzene, n-butyl acetate, n-butanol and n-isoamyl acetate) at 80 degrees C, a polydimethylsiloxane-coated SPME fiber was exposed to the headspace of the vial to allow adsorption of the compounds. The fiber needle was then injected into a capillary gas chromatography (GC) port. The headspace SPME-GC gave intense peaks for each compound and a low level of background noise was seen only for whole blood. Recovery rates of the 5 compounds by use of the headspace SPME-GC were 50-70%. Reproducibility for headspace SPME-GC data were excellent for both body fluids. The calibration curves showed linearity in the range 2-100 ng/0.5 ml whole blood or urine. The detection limits of each compound were 1.1-2.4 ng/0.5 ml sample. The present results on the analysis of 5 thinner components by headspace SPME-GC suggest its applicability to a number of other volatile compounds in forensic toxicology.
1-Butanol↗
Influence of histamine on the bradykinin response of canine testicular polymodal receptors in vitro.
Effects of histamine on the testicular polymodal receptors were studied in vitro using canine testis-spermatic nerve preparations. Histamine induced distinct increase in the discharge rate in 6 out of 17 units tested (high responders), while it only weakly excited the remaining 11 units (low responders). The bradykinin response of low responders tended to be slightly facilitated by pretreatment with histamine, while that of high responders tended to be suppressed. Significant correlation was observed between the magnitude of histamine-induced discharges and the magnitude of change in the bradykinin responses.
Animals↗
Cardiac effects of methylmethacrylate in the rat heart-lung preparation with or without volatile anesthetics.
We have assessed the deleterious effects of methylmethacrylate (MMA) on cardiac function and metabolism in the isolated heart-lung preparation with or without volatile anesthetics. Wistar rats were prepared for the heart-lung model. They were randomly divided into 5 groups as follows. (1) Control (C) group. (2) Cement (M) group; they received MMA. (3) Halothane (H) group; they received MMA and 1% halothane. (4) Isoflurane (I) group; they received MMA and 1.5% isoflurane. (5) Sevoflurane (S) group; they received MMA and 2.5% sevoflurane. MMA 1000 micrograms/ml was administered 7 min after the start of perfusion except in the C group. At the end of the experimental period, the hearts were freeze-clamped and then myocardial high energy phosphates, lactate and glycogen were measured. Cardiac output in all groups but C group decreased significantly. PO2 of the perfusion blood in the M, H, I and S groups was significantly lower than that in the C group. Myocardial ATP in the M, H, I and S groups was significantly lower than that in the C group. ADP and AMP in the M, H, I and S groups were higher than those in the C group. There were no significant differences in lactate and glycogen levels between the 5 groups. MMA 1000 micrograms/ml is much higher than the blood level (0.05-31.89 micrograms/ml) which was reported in clinical patients who had femoral prosthesis. Therefore, the direct contribution of MMA itself to cardiac depression may be less than the other factors such as embolism in clinical situations. Volatile anesthetics did not influence the deleterious effects of MMA on cardiac function and metabolism.
Anesthetics↗
Comparative effects of halothane, enflurane, isoflurane and sevoflurane on function and metabolism in the ischaemic rat heart.
This study was designed to examined the effects of inhalation anaesthetics on function and metabolism in isolated ischaemic rat hearts. Four volatile anaesthetics in two different concentrations (1.0 to 1.5 MAC) were used before whole heart ischaemia was induced for 15 min followed by reperfusion for 30 min. The data were compared with a control group in which inhalation anaesthetics were not used. Before ischaemia, volatile anaesthetics depressed ventricular function. During reperfusion, ventricular function and coronary flow in both halothane groups were significantly lower than those in the control group. Myocardial ATP concentrations in the 1.0 MAC of enflurane and isoflurane groups were significantly higher than those in the control group. We conclude that halothane had more depressant effects than the other anaesthetics and that enflurane and isoflurane may enhance metabolic recovery in the ischaemic working rat heart.
Adenosine Triphosphate↗
Isoflurane and sevoflurane produce a dose-dependent reduction in the shivering threshold in rabbits.
All general anesthetics markedly impair thermoregulatory responses; nonetheless, sufficient hyperthermia or hypothermia will trigger most protective reflexes. Shivering, however, remains an exception among thermo-regulatory responses: it is common during postanesthetic recovery, but is rare at typical anesthetic concentrations. This observation suggests that general anesthesia impairs shivering far more than other thermoregulatory defenses. Accordingly, we tested the hypothesis that low concentrations of isoflurane and sevoflurane would virtually obliterate shivering. Japanese white rabbits were anesthetized with isoflurane or sevoflurane at end-tidal concentrations of 0.2, 0.3, and 0.4 minimum alveolar anesthetic concentration (MAC) (n = 6 in each group); the normal core temperature for these rabbits is approximately 39 degrees C. Core temperatures were subsequently reduced by a water-perfused thermode positioned in the colon. The core temperature triggering shivering identified the threshold for this response. Five of the six rabbits given 0.2 MAC isoflurane shivered at a mean core temperature of 36.3 +/- 0.3 degrees C (mean +/- SD), and one rabbit failed to shiver at a minimum core temperature of 35.0 degrees C. Four of the six rabbits given 0.3 MAC isoflurane shivered at a mean core temperature of 36.2 +/- 0.6 degrees C, and two of these rabbits failed to shiver at a minimum core temperature of 35.0 degrees C. However, no rabbit given 0.4 MAC isoflurane shivered, even at minimum core temperatures of 35.0 degrees C. All of the rabbits given 0.2 MAC sevoflurane shivered at a mean core temperature of 36.6 +/- 0.7 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthetics↗