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Biomedical subjects

R Y Sun

Publications and source records attributed to R Y Sun.

At least 19 recordsLinked to original sources

Quantitative design of optimal analgesic combination of acetaminophen, caffeine, and butalbital.

AIM: To quantitatively seek an optimal analgesic combination of acetaminophen (Ace), butalbital (Bul), and caffeine (Caf), and to characterize the pharmacodynamics of interaction among the three drugs. METHODS: The models of acute inflammatory pain in carrageenin-injected rats were applied to measure the vocalization threshold to paw pressure. Six groups with different ratios and doses were set to seek an optimal combination of Ace, Caf, and Bul, analyzed by the weighted modification method. Based on the ratio and doses in the optimal combination, four continuous doses were set to analyze the interactions of therapeutic effects by the reflection method. The interaction of the acute toxicity was evaluated by the parameter method. RESULTS: According to the degree of importance to the combined analgesic effect, Ace > Caf > Bul; Ace showed a significant dose-response relationship, whereas in Caf and Bul, this relationship was not apparent. A new combination was obtained by the theoretical analysis and confirmed further by experimentation. Namely, at a ratio of 8.6:1:1.5 Ace + Caf + Bul (240 + 28 + 42 mg/kg, ig) was an optimal combination. Both Caf and Bul had a synergism to Ace, but Caf was a stronger synergist in contrast to Bul. Such synergism increased the therapeutic effects in the range of Ace 153.6 - 300 mg/kg combined with Caf 17.9 - 35 mg/kg and Bul 26.8 -5 2.5 mg/kg (8.6:1:1.5). However, the dose of Ace + Caf + Bul at 300 + 35 + 52.5 mg/kg resulted in sedation in rats. The peak latency was approximately 1 h for all four continuous doses, but the peak amplitude was dose-related, and the duration of the therapeutic effect was less than 2 h. The acute toxicity of the three drugs in combination remained the same. CONCLUSION: Ace + Caf + Bul at a dose of (240 + 28 + 42) mg/kg (ig) results in an optimal combination. The therapeutic window of the combination is located in the range of Ace (153.6 - 240 mg/kg)+Caf (17.9 - 28 mg/kg)+Bul (26.8 - 42 mg/kg) (8.6:1:1.5). Caf has a stronger synergism with Ace than Bul.

Acetaminophen↗

Effect of pH and Zn(2+) on subcultured muscle cells from Macrobrachium nipponense.

A cell culture system was devised for muscle cell of Macrobrachium nipponense in the study. The juvenile and adult shrimps were held in laboratory aquaria with penicillin 1000 IU/ml and streptomycin 1000 microg/ml for 12-24 hours. Cell cultures were established in medium 199 supplemented with 20% fetal bovine serum, 1 g/L glucose, 5.2 g/L NaCl, 1.43 g/L CaCl(2), 0.05 g/L MgCl(2), 100 IU/mL penicillin and 100 microg/ml streptomycin. Fibroblast-like cells were passaged up to three times and survived for 54 days. The results showed the optimum for subculture in vitro was in medium 199 with pH 7.6. Moreover, basal medium supplemented with Zn(2+) 60 microg/L could enhance the growth of the muscle cells. It was found that better results for cell culture would be obtained more easily with juvenile shrimps caught in spring than adults in summer or autumn; and shrimps caught within 12 hours after ecdysis could grow much better than the intermoult shrimps.

Animals↗

Analysis of drug interactions in combined drug therapy by reflection method.

AIM: To set up a new method to analyze multidrug interaction in combined drug therapy. METHODS: Based on a dose-effect curve of the combined drugs and the equieffective test, a new mathematical model was set as Q = (Eo - Et)/L (-1 < Q < 1 addition, Q < or = 1 antagonism, Q > or = 1 synergism) where Eo = an observed value (or its fitted value) of combined effect, Et = an expected value of combined effect, and L = an equieffective cutoff between Eo and Et, decided by the equieffective criterion of a special field, the number of data points, and the experimental error. The different types of experimental data were analyzed by the new model. RESULTS: This reflection method could deal with data in combined drug therapy, unnecessary to distinguish between independent and similar action, or exclusive and non-exclusive case among drugs. The number of drugs for combination did not need to be limited. But the experimental data should be enough to fit a dose-effect curve of drugs in combination. If every dose-effect curve of drugs for combination was made, a series of Q values was obtained from all levels of dose-effect for a systematic analysis. To large animal or human experiment, the points of dose-effect of each drug used alone could be reduced to even 1 point. The results of analysis took the criterion of a special field and laboratory error into account in this method. CONCLUSION: The reflection method is an effective method for analysis of multidrug interaction in combined drug therapy.

Animals↗

Quantitative design of drug compatibility by weighted modification method.

AIM: To set up a new method for designing and quantitatively analyzing drug compatibility. METHODS: Drugs for compatibility were divided into 6 dose levels which were evenly distributed to 6 compound groups according to a fixed design. A new mathematical model was set up to fit the dose-effect data of 6 groups. The coefficients, obtained from the model, reflected the dose-effect relationship and the important degree of every drug in combination. According to the coefficients, the drugs in compatibility could be distinguished into principal drug, synergist, inferior, antagonist, and assistant. Because compatibility in the maximal effect group was nearly (or was) an optimal one in 6 groups, the doses in the group were taken as a base for further modification which considered interaction among drugs. The results of the modification were demonstrated by further experiment. This method was applied to design and to quantitatively analyze the compatibility of allantoin, metronidazole, and dexamethasone sodium phosphate by 2 effect indices in mice. RESULTS: This new method was able to effectively determine important degree of drugs in combination, and to optimize their doses for designing compatibility. CONCLUSION: This weighted modification method is a highly efficient, accurate, and practical means for designing and quantitatively analyzing drug compatibility.

Allantoin↗

Uncoupling protein mRNA, mitochondrial GTP-binding, and T4 5'-deiodinase activity of brown adipose tissue in Daurian ground squirrel during hibernation and arousal.

The mRNA level of uncoupling protein (UCP) specific for brown adipose tissue (BAT) in Daurian ground squirrel, was detected by using a [32P]-labeled oligonucleotide probe. The UCP concentration in mitochondria was indirectly determined by titration with its specific ligand [H3]-labeled GTP. Type II T4 5'-deiodinase of BAT was assayed concomitantly. We found two species of mRNA for UCP with lengths of about 1.9 and 1.5 kb, respectively, both occurring in almost the same concentration. UCP mRNA content was elevated significantly during hibernation, but the UCP concentration did not change compared with that of nonhibernating controls kept at room temperature. When hibernating squirrels were aroused, the UCP mRNA remained at the elevated level as during hibernation, but the UCP concentration increased in comparison with that of nonhibernating controls or during hibernating. Changes in T4 5'-deiodinase activity in BAT were similar to the variations of the UCP mRNA level. These results suggest that the activation of T4 5'-deiodinase in BAT may be an important factor for the up-regulation and maintenance of UCP mRNA content needed for the synthesis of sufficient UCP to acquire the thermogenic capacity for arousal from hibernation.

Adipose Tissue↗

Analysis of multidrug effects by parameter method.

AIM: To set up a new analytic method for multidrug effects. METHODS: Based on the principles of the target site kinetics and the equieffective test, a new mathematical model was set as Q = (Eo-Ee)/magnitude of Ee x W-sx x T (-1 < Q < 1 addition, Q < or = -1 antagonism, Q > or = 1 synergism) where Eo = a fitted value of the observed effect of a combination, Ee = an expected value of combined effect, W = an equieffective criterion decided by a special field, sx = a common standard error of Eo and Ee, and T = a value of one-sided t0.05. All the calculations were completed with computer. Dose-effect data from different types of experiments were fitted by the new model and the results were compared with those of other methods. RESULTS: This parameter method dealt with different types of data well fitted with the Hill equation, and was not limited to analyze receptor interaction of drugs, or the number of combined drugs. A series of Q values was obtained from all levels of dose-effect for a systematic analysis. The analysis took the criterion of a special field and laboratory error into account. CONCLUSION: This parameter method can effectively analyze the multidrug effects.

Acetylcholine↗

[Effect of enterogastric circulation of diazepam on its CNS inhibitory action in mice].

The present study was designed to examine whether disturbance of the enterogastric circulation of diazepam would obviously affect its inhibitory action on CNS. Intragastric administration of acidic liquid (pH 1) elicited a marked increase in the amount of diazepam in the gastric juice of mice 1 h after i.v. diazepam, as measured by HPLC method. The effects of ig acidic charcoal (2 g.kg-1, pH 1), neutral charcoal and normal saline on diazepam-induced CNS depression were compared by studying the duration of hypnotic action, inhibition of spontaneous activity, dropping rate in rotating rod test and mortality after i.v. diazepam (10-40 mg.kg-1) in mice. The results showed that the animals receiving ig acidic charcoal recovered more rapidly from CNS depression and exhibited lower mortality than the animals in neutral charcoal group and normal saline group.

Animals↗

Orthogonal analysis of aggravating effects of alpha-, beta-agonists and leukocytes on reperfusion-induced arrhythmias and ventricular fibrillation in Langendorff's rat heart.

AIM: To study the effect of leukocyte (Leu), alpha-agonist (alpha-Ago), and beta-agonist (beta-Ago) on the arrhythmias induced by ischemia and reperfusion to determine which of the 3 factors was the most important one in exacerbating arrhythmias. METHODS: Arrhythmias were induced by the reduction and subsequent resumption of perfused flow in Langendorff's perfused rat hearts. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded on ECG, and the results were orthogonally analyzed. RESULTS: When Leu was present, the incidence of VF induced by ischemia-reperfusion was 80%. The incidence in Leu-depleted hearts was 20%, alpha-Ago and beta-Ago elevated it to 60% and 100%, respectively. The results by orthogonal analysis demonstrated Leu or alpha-Ago+ beta-Ago increased VF incidence. With regard to arrhythmias, arrhythmia score was remarkedly increased by all of 3 factors and various combinations except beta-Ago + Leu. CONCLUSION: Among these 3 factors, Leu was the most important one in facilitating reperfusion-induced arrhythmias.

Adrenergic alpha-Agonists↗

[Pharmacokinetic analysis of enterogastric circulation of diazepam in rabbits].

The concentration-time curves of diazepam exhibited double peaks after i.v. 5 mg.kg-1 to 6 rabbits. A pharmacokinetic model taking account of enterogastric circulation was proposed to explain this double-peak phenomenon and showed good agreement with data. This model provides not only the ordinary pharmacokinetic parameters: T1/2 (alpha) = 0.21 +/- 0.15 h, T1/2 (beta) = 2.2 +/- 0.6 h, Ke = 1.5 +/- 0.6 h-1, K12 = 2.0 +/- 1.0 h-1, K21 = 1.0 +/- 0.4 h-1, V1 = 3.1 +/- 1.6 L.kg-1, AUC = 1.7 +/- 0.5 microgram.h-1.ml-1, but also the parameters of enterogastric circulation of diazepam: lag time of reabsorption T' = 0.25 +/- 0.24 h, reabsorption rate constant Ka = 3.5 +/- 1.4 h-1, reabsorption rate Ra = 24 +/- 7%.

Animals↗

Second peak of plasma diazepam concentration and enterogastric circulation.

Intragastric food administration caused a pronounced second peak of plasma diazepam concentration in rabbits after iv diazepam 5 mg.kg-1. The second peak disappeared after gastrostomy and choledochostomy. A large amount of diazepam was found in the gastric juice while its content in bile remained at a much lower level during the whole experiment. These results suggested that diazepam may undergo an enterogastric circulation in addition to its enterohepatic circulation, with the former mainly contributing to the appearance of the second peak.

Animals↗

[Effect of activated leukocytes on pulmonary arterial pressure].

Shock model was established by intravenous injection of E Coli endotoxin with a dosage of 5 mg/kg wt in dog. An immediate fall in systemic arterial pressure (SAP) was found after injection, while an increase in pulmonary arterial pressure (PAP) and a markedly leukopenia in circulatory blood were also found. Rats lung was perfused with warm (37 degrees C) krebs solution in constant flow rate. There was an obviously increase in PAP when activated leukocytes had been added to the perfusion solution. The results suggested that activated leukocytes in the lung blood vessels may play an important role in the pathogenesis of pulmonary hypertension.

Animals↗

[Site of endotoxic pulmonary vasoconstriction and the effect of anisodamine].

Using arterial and venous occlusion techniques in an in situ, isolated left goat lung preparation, the total arteriovenous pressure drop across the lung was partitioned vertically into pressure drops across the relatively indistensable arteries (delta Pa) and veins (delta Pv) and the middle distensible vessels (delta Pm). Endotoxin primarily increased delta Pv and Pc. Anisodamine only showed a slight effect on pressure drops in different segment under normal conditions. It could attenuate the endotoxin effect however. Serotonin mainly increased delta Pa and showed no effect on delta Pv and delta Pm. Norepinephrine and histamine increased delta Pv and Pc while it showed almost no effect on delta Pa. It is possible that the norepinephrine and histamine mediate the pulmonary hypertension caused by endotoxin.

Animals↗

Role of beta-receptor in the radix Angelicae sinensis attenuated hypoxic pulmonary hypertension in rats.

Acute pulmonary hypertension was caused by inhalation of 5% O2 in rats. Pulmonary vascular resistance (PVR) increased, but heart rate (HR), cardiac output (CO) and carotid arterial pressure (CAP) were not obviously changed. After an intravenous administration of Radix Angelicae sinensis, the acute pulmonary hypertension induced by inhalation of 5% O2 could be attenuated, but this effect disappeared if propranolol was given before Radix Angelicae sinensis. In chronic experiments, the same results were obtained, but the protective effect of Radix Angelicae sinensis on heart function was not influenced by propranolol. It is suggested that Radix Angelicae sinensis might play a role by stimulating the beta 2-receptor in the prevention of acute and chronic hypoxic pulmonary hypertension. However, prevention of hypertrophy of the right ventricle and enhancement of heart function in chronic hypoxic rats might not be attributed to the beta 1-receptor in the heart.

Adrenergic beta-Agonists↗

[Observation on the development of Plasmodium falciparum in Anopheles dirus].

This paper is a record of our observation on the stages of development of Plasmodium falciparum in Anopheles dirus. The malarial parasites were derived from 5 infected patients living in Guizhou Province and used to infect 8 batches of An.dirus. The morphology of various developmental stages studied under light microscope and their average size were as follows: Microgametes were filament-shaped, 13.31 +/- 2.22 microns; macrogametes and zygotes oval or round, 4.36 +/- 0.59 microns and 3.39 +/- 0.39 microns respectively; ookinetes banana shaped, 13.56 +/- 0.80 microns x 2.90 +/- 0.48 microns; oocysts ovoid or spherical in shape, the smallest one being 7.086 microns in equivalate diameter (2 days old) and the largest one 72.60 microns (11 day old); slender sporozoites measured 10.625 +/- 0.82 microns x 1.179 +/- 1.3 microns. The late sporogonic stage of P. falciparum was observed with scanning electron microscope. The sporozoite buds developed on the surface of the sporoblast bodies, being round or elliptic or irregular-shaped. The anterior end of sporozoites was truncate and sometimes a micropyle could be seen at a distance 1/3 from the anterior end. A description was given of the different characteristics of the macrogametes and zygotes, together with the arrangement of the pigment granules of oocysts.

Animals↗