Impact of a systematic education model for palliative care in cancer.

In clinical practice, pharmacists are continually required to improve their knowledge and expertise; however, the postgraduate education system for professional development cannot be confidently stated to be well established. The establishment of a systematic and multifaceted educational curriculum should be useful to improve home care and pharmacists' contribution; therefore, we developed a curriculum in collaboration with the university faculty of pharmaceutical sciences, department of pharmacy in hospital, and the Fukuoka Pharmaceutical Association. Class topics were extracted from the "Kanwa-Iryou-Yakugaku", edited by the Japanese Society for Pharmaceutical Palliative Care and Sciences. The items are necessary to perform palliative care as a pharmacist. A class schedule of 6 days (24 classes in total) was formulated. Questionnaires on comprehension degree before and after each class were provided to the participants. Comprehension was assessed on a scale of 1 to 10, where "I do not understand at all" was 1 and "I understand enough" was 10. The average recovery rates of questionnaires from each class were 92.6 % and 88.9 % before and after class, respectively. The average number of participants who completely answered the questionnaire before and after class was 45.6; therefore, these data were analyzed. Comprehension degree on each topic had significantly increased after attendance of all classes (p < 0.01). The comprehension degree of participants of the medical science of palliative care did greatly improve. Consequently, it is clear that the standard education model constructed was meaningful for the professional development of pharmacists in palliative care medicine.

Mechanism and properties of inhibition of purified rat brain adenylate cyclase by G protein beta gamma-subunits.

The mode of the inhibition of purified rat brain adenylate cyclase by the beta gamma-subunits of G protein (beta gamma) was studied. These subunits inhibited the catalytic activity of the cyclase with the maximal inhibition of 85% and the half-maximal inhibition at about 0.7 nM beta gamma. The complex of beta gamma and adenylate cyclase isolated by density gradient centrifugation contained 1.8-2.0 mol beta gamma per mol of the cyclase when beta gamma was assayed by immunoblotting and by its inhibitory activity on adenylate cyclase. However, the beta gamma concentration-inhibition curves suggest that one of the two beta gamma molecules bound may be essential for the inhibition. The role for the second beta gamma molecule is unknown. As a tentative estimate, 70% of the adenylate cyclase activity remained inhibited by beta gamma when the complex was isolated. The inhibition was not dependent on G alpha s or calmodulin. Although purified adenylate cyclase contained a protein (0.06-0.08 mol/mol of adenylate cyclase) that reacted with anti-G alpha s antibody, this protein was not liberated from the cyclase when it formed a complex with beta gamma. In addition, guanine nucleotide analogs little affected the cyclase activity or the inhibition by beta gamma. The inhibition by beta gamma was reversed by the dilution of the complex, and the following re-addition of beta gamma suppressed the enzyme activity to about 15% of the initial activity again. These findings provide strong evidence that beta gamma inhibits adenylate cyclase directly and reversibly through the formation of the complex.

[Properties and activation by lysophospholipids and fatty acid of membrane-bound guanylate cyclase in lymphocytes and erythrocytes from mouse spleen].

To clarify the properties of membrane-bound guanylate cyclase of lymphocytes and a functional role of lysophospholipids, the enzymic properties of membrane-bound guanylate cyclase and the effects of lysophospholipids and a free fatty acid with Ca2+ on the cyclase in lymphocyte and erythrocyte membrane fractions prepared from mouse splenic whole cells were examined. The membrane-bound guanylate cyclase activities of lymphocyte and erythrocyte membrane fractions from splenic whole cells were activated markedly by several lysophospholipids and linoleate. Lysophospholipids were divided into three groups according to their effects on the cyclase. 1) The first group of lysophospholipids exhibited the concentration-activity curve which was similar to that of linoleate. 2) The second group showed the curves which were markedly different in the presence and absence of Ca2+. 3) The third group had no effects on the enzyme activity. The membrane-bound guanylate cyclase activity in the erythrocyte membrane fractions was about 2 times stronger than that in the lymphocyte fractions. On the other hand, the membrane-bound guanylate cyclase activity in the erythrocyte fractions from peripheral blood was not enhanced by these substances. The marked activation of the guanylate cyclase by lysophospholipids and linoleate is considered to have important significance in the regulation of cGMP-mediated signal transduction.

Effects of calcium channel agonists (BAY K 8644, CGP28392 and YC-170) on 45Ca uptake by rat uterine segments.

The characteristics of the stimulating effects of the calcium channel agonists BAY K 8644, CGP28392 and YC-170 on 45Ca uptake by rat uterine segments were investigated. BAY K 8644, CGP28392 and YC-170 caused about 150, 100 and 150% increase, respectively in the 45Ca uptake induced by 20 mM KCl. The ED50 values of BAY K 8644, CGP28392 and YC-170 were 1.8 X 10(-9), 2.5 X 10(-8) and 9.8 X 10(-9) M, respectively. These agonists had little effect on the 45Ca uptake induced by 10(-6) M acetylcholine. They also did not affect the basal 45Ca uptake. Their enhancing effects were blocked by the Ca channel antagonist nitrendipine. We conclude that rat uterine segments have voltage-sensitive Ca channels that are stimulated by Ca channel agonists (BAY K 8644, CGP28392 and YC-170) under depolarizing conditions and that the characteristics of the stimulating effects of CGP28392 and YC-170 on 45Ca uptake by rat uterine segments are qualitatively the same as those of BAY K 8644.

Enhancement by L-methionine on the contractile response of uterine segments to acetylcholine and high KCl is mainly due to enhancement of Ca uptake.

Acetylcholine (ACh)- and high KCl-stimulated 45Ca uptake into rat uterine segments was inhibited by 3-deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL), and this inhibitory effect was attenuated by L-methionine (L-Met). Ca-depleted Ringer solution in which uterine muscle had been incubated with L-Met did not enhance the contractile response of another uterine segment to ACh and high KCl in the presence of 3-DAA plus HCTL. These findings together with previous results suggest that the enhancing effect of L-Met on the contractile responses to ACh and high KCl is mainly due to an increase in Ca2+ uptake into the uterine muscle.

[Anesthetic management of a patient with acromegaly complicated with hyperthyroidism].

A rare anesthetic experience of a 30-year-old woman with acromegaly complicated with Basedow's disease is reported. After the thyroid function was successfully controlled by drug therapy, resection of pituitary adenoma was performed under general anesthesia. Anesthesia was induced and maintained with NLA. No problem was observed during the operation and postoperative period. Careful attention should be paid to the management of circulation, respiration, metabolism and endocrinium through the perioperative period.

Characteristics of acetylcholine-induced phosphorylase a activity in uterine segments as a substitute for contractile response to acetylcholine.

Studies were made on whether the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could be used as a substitute for the contractile response to ACh. This ACh-induced phosphorylase a activity was dependent upon the concentration of ACh and was inhibited by atropine, suggesting that it was linked to muscarinic ACh receptors. Both extracellular calcium and an increase of the intracellular calcium concentration were needed for its activation by ACh. Ca2+-antagonists such as Co2+, diltiazem, nitrendipine and verapamil inhibited the ACh-induced activity, suggesting that the activation by ACh required the influx of calcium ions into the uterine muscle through Ca2+-antagonist sensitive Ca2+ channels. The IC50 values of CoCl2, diltiazem, nitrendipine and verapamil on the ACh-induced phosphorylase a activity were 3.4 x 10(-3) M, 2.5 x 10(-4) M, 2.5 x 10(-5) M and 1.1 x 10(-4) M, respectively. These values were comparable with the IC50 values of these Ca2+-antagonists on the contractile response of isolated rat uterine muscle segments to 3 x 10(-4) M ACh. The inhibitory effects of Co2+, nitrendipine and verapamil, but not diltiazem, on ACh-induced phosphorylase a activity were attenuated by higher concentrations of CaCl2 (0.36 to 2 mM). These findings suggested that the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could be used as a substitute for the contractile response to ACh.

General characteristics of the superprecipitation reaction of rat crude uterine myosin B: effects of L-methionine and/or transmethylation blockers on the reaction.

The characteristics of superprecipitation of uterine myosin B from 17 beta-estradiol-3-benzoate-treated rats and the effects of L-methionine and/or 3-deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL) on the reaction were investigated. The slope and plateau phases of the superprecipitation were dependent on ATP, calcium and magnesium. The calmodulin antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide, inhibited the slope and plateau phases, but not the basal superprecipitation. SDS-polyacrylamide gel electrophoresis of the precipitate obtained in complete medium showed the presence of actin and myosin. Addition of 3 mM L-methionine had little affect on either the slope or plateau phases of the basal- or calcium-dependent superprecipitation, while 500 microM 3-DAA plus 1 mM HCTL caused only 9 to 20% decrease in the calcium-dependent superprecipitation in the presence of 0.1 mM or 1 mM ATP. These findings suggest that the calcium-dependent superprecipitation of rat uterine myosin B reflected the contractile response of uterine muscle, and that L-methionine and/or 3-DAA plus HCTL did not affect the calcium-dependent superprecipitation of uterine myosin B.

L-methionine enhances the contractile response to norepinephrine of rat vas deferens.

Under Ca-depleted conditions, the contractile responses of rat vas deferens in the presence of norepinephrine were not elicited until the addition of CaCl2. L-Methionine enhanced the contractile response of vas deferens in the presence of methylation blockers under these conditions. The enhancing effect of L-methionine on some other smooth muscles could not be determined because under Ca-depleted conditions, these muscles showed 60-80% of the maximal contractile response on addition of CaCl2 alone. These findings suggested that L-methionine has an enhancing effect on contraction of the rat vas deferens as it does on rat uterine muscle.

Enhancement by L-methionine of contractile responses to acetylcholine and high KCl in uterine segment.

The contractile responses of isolated uterine segments from 17 beta-estradiol-3-benzoate-treated ovariectomized rats to acetylcholine (ACh) and high KCl in Ca-depleted modified Locke-Ringer solution on addition of CaCl2 were used as indicators of Ca2+ influxes through ACh receptor- and voltage-operated Ca2+ channels, respectively. L-Methionine (L-Met) significantly enhanced these responses. The enhancement depended on the time of treatment with L-Met and concentration of L-Met. 3-Deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL), which inhibit S-adenosylmethionine-dependent methylation, caused dose-dependent inhibition of these contractile responses to ACh and high KCl. These inhibitory effects of 3-DAA plus HCTL were significantly attenuated in the presence of L-Met. Protein carboxylmethyltransferase and phospholipid methyltransferase activities were detected in the isolated uterine segment under conditions similar to those in which the contractile responses were observed. 3-DAA plus HCTL inhibited these enzyme activities. These findings suggest that S-adenosylmethionine-dependent methylations of protein and/or phospholipid in isolated uterine segment are involved in the contractile responses to ACh and high KCl in Ca-depleted modified Locke-Ringer solution on addition of CaCl2.

Comparison of the nutritive values of L-, DL- and D-tryptophan in the rat and chick.

Experiments were designed to compare the nutritive values of L-, DL- and D-tryptophan in rats and chicks. Growing rats and chicks were fed for 19 and 21 days, respectively, diets containing amino acid mixtures with graded levels of either L-, DL- or D-tryptophan so that the regression of weight gain or protein retention on tryptophan intake could be established. After the end of the experiments, plasma free L-tryptophan was estimated by a microbiological method. The nutritive values of DL- and D-tryptophan relative to the L-isomer were 47 and 21%, respectively in chicks and close to 100% in rats. In chicks, plasma free L-tryptophan concentration increased with the increase of L- and DL-tryptophan levels in the diet, but remained at a low level regardless of the D-tryptophan level in the diet. In rats, however, a good correlation was observed between plasma free L-tryptophan and tryptophan level in the diet.

Inversion of D-tryptophan to L-tryptophan and excretory patterns in the rat and chick.

The behavior of D-tryptophan in the blood plasma and the pattern of tryptophan excretion in the urine were studied in the rat and the chick. When D-tryptophan was administered orally to rats and chicks, both showed D-tryptophan in the plasma. Conversion of D-tryptophan to the L-isomer in the rat was found by an examination of plasma from the posterior vena cava and the portal vein, following stomach intubation of 100 micromoles D-tryptophan/100 g of body weight. The peak in the increase of L-tryptophan was approximately 150 nmoles/ml plasma when measured at 30 minutes after administration and the peak was 200 nmoles when measured 2 hours after administration. No conversion of D-tryptophan to the L-isomer was found in chicks. Under similar conditions, D-tryptophan was measured in the urine of rats and chicks. In rats the D-tryptophan excreted was at most 1% of the amount administered; while in chicks most of the D-tryptophan was excreted.

Nutritive value of L-, DL- and D-tryptophan in the chick.

The present study was undertaken to determine the nutritive value of L-, DL- and D-tryptophan in chicks. Day-old chicks were fed commercial chick starter ration for one week and then they were given an experimental diet containing zein as a protein source for three weeks. The experimental results were analyzed by a slope ratio technique (weight gain vs. tryptophan intake). The relative biological utilization of DL- and D-tryptophan compared to L-tryptophan was approximately 55 and 15%, respectively. At the end of the experiment, the chicks were sacrificed and the concentration of free tryptophan in plasma was measured. The free tryptophan concentration in plasma corresponded closely with the increment level of tryptophan in diet when there was a normal level of dietary protein. But there was less correspondence when chicks were fed a diet low in protein.