Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria

To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode’s solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement transducer. Perfusate potassium concentrations were increased from 5.4 mmol · L⁻¹ to either 8.1 mmol · L⁻¹ or 10.8 mmol · L⁻¹ by adding KCl to the standard Tyrode’s solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate. In standard Tyrode’s solution (potassium 5.4 mmol · L⁻¹, pH 7.4), halothane 0.5–2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of halothane for 50% inhibition of contractile force (IC₅₀) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium-or pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas 1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis (pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria. The increase in resting tension observed during acidosis/ halothane conditions suggests than an increase in cytosolic calcium is associated with these synergistic interactions between acidosis and halothane. Pour mieux comprendre l’action direct de l’halothane sur la fonction myocardique pendant l’ischémie, nous avons étudié les effets de l’augmentation du potassium extracellulaire et de la diminution du pH extracellulaire (acidose), seuls ou en association avec l’halothane, sur la force contractile et la tension de repos d’oreillettes isolées. Des oreillettes gauches de cobaye furent perfusées avec une solution de Tyrode et stimulées à 1 Hz. La force contractile isométrique et la tension de repos ont été mesurées avec un transducteur de force de déplacement. Les concentrations de potassium perfusées ont été augmentées de 5,4 mmol · L⁻¹ à 8,1 mmol · L⁻¹ ou à 10,8 mmol · L⁻¹ par l’ajout de KCl à la solution standard de Tyrode, et son pH abaissé de 7,4 à 7,0 ou 6,5 par baisse des bicarbonates. Avec la solution standard de Tyrode (potassium 5,4 mmol · L⁻¹, pH 7,4), l’halothane (0.5–2%) diminue la force contractile proportionnellement à la dose (P < 0,05); la concentration efficace d’halothane requise pour produire une inhibition de 50% de la force contractile (IC_5O) a été de 1,3%. L’augmentation du potassium extracellulaire et la diminution du pH extracellulaire réduisent toutes les deux la force contractile proportionnellement au potassium ou au pH. L’inotropisme négatif de l’halothane (1%) n’est pas modifié par l’augmentation de la concentration de potassium alors que l’halothane produit une diminution plus importante de la force contractile à un pH de 6,5 que de 7,4. L’halothane (1%) exagère l’augmentation de la tension de repos induite par l’acidose (pH 6,5). Des arrythmies sont apparues sur une des huit préparations pendant l’acidose en présence d’halothane. Ces données suggèrent que l’acidose et l’halothane pourraient avoir une activité synergique sur le force contractile et la tension de repos des oreillettes. L’augmentation de la tension de repos observée pendant l’acidose combinée à l’halothane suggère l’association d’une augmentation du calcium cytosolique avec des interactions synergiques entre l’acidose et l’halothane.     

The medicine chest handed down in the Takaya family, doctors of Sendai-han

There is a medicine chest with design of Chrysanthemums in Makie made for Edo-era and handed down in the Takaya family, doctors of Sendai-han. Many kinds of crude drugs, named by one Chinese character, are kept in this chest. They were classified into three types, namely, [Japanese characters]. Identification of these crude drugs was carried out and the meaning of the classification was brought up as a question.     

Correlates of individual differences in body-composition changes resulting from physical training in obese children

BACKGROUND: No studies have been reported in children that assess correlates of body-composition changes in response to a physical training intervention. OBJECTIVE: The hypothesis studied was that variation in diet and physical activity would explain a significant portion of the interindividual variation in the response of body composition to physical training. DESIGN: The participants were 71 obese children aged 7-11 y (22 boys, 49 girls; 31 whites, 40 blacks). Body composition was measured by dual-energy X-ray absorptiometry, physical activity by a 7-d recall interview, and diet by two, 2-d recalls. The children underwent 4 mo of physical training. RESULTS: The mean attendance was 4 d/wk, the mean (+/-SD) heart rate for the 40-min sessions was 157 +/- 7 beats/min, and the mean energy expenditure was 946 +/- 201 kJ/session. On average, the percentage body fat decreased significantly in the total group, and total mass, fat-free soft tissue, bone mineral content, and bone mineral density increased, but there was a good deal of individual variability. Multiple regression models indicated that in general, more frequent attendance, being a boy, lower energy intake, and more vigorous activity were associated with healthier body-composition changes with physical training. Ethnicity was not retained as a correlate of the change of any component of body composition. CONCLUSIONS: In obese children, age, vigorous activity, diet, and baseline percentage body fat together accounted for 25% of the variance in the change in percentage body fat with physical training.     

Iodine-123-MIBG scintigraphy in neuroblastoma; relationship between the intensity of uptake and tumor characteristics

Iodine-123-MIBG (123I-MIBG) scintigraphy were performed for 23 patients with neuroblastoma at diagnosis. The intensity of MIBG activity in the primary tumor was evaluated visually (grade 3; intense uptake-grade 0; no definite uptake), and its relationship to the size, degree of tumor spread, urinary catecholamine metabolites (VMA, HVA), and histological types were investigated. The results of 123I-MIBG uptake grade were as follows: grade 3; 44% (10/23), grade 2; 30% (7/23), grade 1; 17% (4/23), grade 0; 9% (2/23). The grade was not associated with the tumor size, or the degree of tumor extension to the distant lesion, either. The more catecholamine metabolites were excreted in the urine, the tumor tended to have more intense uptake. The tumors of neuroblastoma rosette fibrillary type, and ganglioneuroblastoma poorly differentiated type had more intense uptake than neuroblastoma round cell type and ganglioneuroblastoma well differentiated type. The case of ganglioneuroma did not have definite MIBG uptake. The intensity of MIBG uptake is not relevant to the pathological grade of neuroblastoma, but considering the electromicroscopical features of neuroblastoma reported previously, it is thought to reflect the histological type.     

Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.

1. Anisatin, a toxic, insecticidally active component of Sikimi plant, is known to act on the GABA system. In order to elucidate the mechanism of anisatin interaction with the GABA system, whole-cell and single-channel patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. 2. Repeated co-applications of GABA and anisatin suppressed GABA-induced whole-cell currents with an EC50 of 1.10 microM. No recovery of currents was observed after washout with anisatin-free solution. 3. However, pre-application of anisatin through the bath had no effect on GABA-induced currents. The decay phase of currents was accelerated by anisatin. These results indicate that anisatin suppression of GABA-induced currents requires opening of the channels and is use-dependent. 4. Anisatin suppression of GABA-induced currents was not voltage dependent. 5. Picrotoxinin attenuated anisatin suppression of GABA-induced currents. [3H]-EBOB binding to rat brain membranes was competitively inhibited by anisatin. These data indicated that anisatin bound to the picrotoxinin site. 6. At the single-channel level, anisatin did not alter the open time but prolonged the closed time. The burst duration was reduced and channel openings per burst were decreased indicating that anisatin decreased the probability of openings.     

Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs

sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.