Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

[Isolation and elucidation of chemical constituents of Shandanshaoyao Decoction(I)].

OBJECTIVE: To study the chemical constituents of Shandanshaoyao Decoction. METHOD: The sample was prepared using boiling water, then precipitated by 75% ethanol. The ethanol soluble fraction was extracted by chloroform, ethyl acetate and n-butanol respectively. The extracts were isolated using silica gel and polyamide column chromatography, and the chemical constituents were identified by chemical and spectroscopic methods. RESULT: Six compounds were isolated from the chloroform and ethyl acetate extracts, and elucidated as tanshinone IIA, benzoic acid, ferulic acid, cryptotanshinone, beta-stitosterol and ursolic acid respectively. CONCLUSION: A preliminary study on the chemical constituents in traditional Chinese compound recipe Shandanshaoyao Decoction is reported.

[Isolation and elucidation of chemical constituents of shandanshaoyao decoction (II)].

OBJECTIVE: To study the chemical constituents of Shandanshaoyao Decoction. METHOD: The sample was prepared by boiling water, then precipitated by 75% of ethanol. The ethanol soluble fraction was extracted by chloroform, ethyl acetate and n-butanol, respectively. The extracts were isolated using macroreticular resin, silica gel and polyamide column chromatography, and then the chemical constituents were identified by chemical and spectroscopic methods. RESULT: Nine compounds were isolated from the n-butanol extract and water soluble fraction, and elucidated as vitexin, quercetin, hyperoside, rutin, paeoniflorin, protocatechaldehyde, (+)-catechin, danshensu and citric acid respectively. CONCLUSION: The chemical constituents of traditional Chinese medicinal preparations Shandanshaoyao Decoction were reported for the first time.

Dietary fat consumption and non- communicable chronic diseases in China.

Fat consumption at a national level is largely determined by the economic development of a country. Based on the data of nationwide nutrition surveys undertaken in China in 1982 and 1992, the average intake per capita per day of meat increased from 62.6 to 100.5 g in urban areas and from 22.9 to 37.6 g in rural areas. The consumption per capita per day of eggs increased from 15.5 to 29.4 g in urban areas and from 3.8 to 8.8 g in rural areas. The daily consumption of cooking oil was 12 g in 1982 and reached 22.4 g in 1992, while the consumption of animal fat remained stable. The average fat intake accounted for 18.1% of total energy intake in 1982 and 22.0% in 1992. The daily fat intake of Beijing urban residents was 92.9 g per capita per day in 1992, accounting for 32.7% of total energy intake, which was beyond the top limit suggested by the World Health Organisation. The change of disease patterns in Chinese people has been great during the past two decades. The mortality rate due to cerebro-cardiovascular disease accounted for 12.07% of deaths in 1957, and increased to 40.72% in 1994. The non-communicable chronic diseases (NCCD) accounted for approximately 70% of total deaths. Twenty-five percent of the total population and 60% of day care patients suffered from chronic diseases. The risk factors of NCCD are increasing in China and more attention should be given to the prevention and intervention of NCCD in the future.

Skin testing in patients with high risk of anaphylactic reactions to penicillin.

Sequential skin testing including immediate patch test (IPT), skin prick test (SPT), and intradermal test (IT) with sodium benzylpenicillin G (Pen G), and SPT with benzylpenicilloyl human serum albumin (BPO-HSA) was done in 58 subjects with a history of probable anaphylactic reaction or shock of unknown cause. Based on positive skin tests, the diagnosis of penicillin anaphylaxis was confirmed in 30 patients. The average age of onset of penicillin allergy was 42 years ranging from 20-70 years. The sex ratio was 2:28 with marked female predominance. Anaphylactic shock, wheezing and urticaria occurred in 21, 20, 19 patients, respectively. Most symptoms were induced by skin tests and inhalation. The results of skin tests in these patients showed that IPT with 500 U/ml of Pen G was not only reliable but also safe. It is suggested that patients suspected of penicillin anaphylaxis should received IPT with 500 U/ml of Pen G as the initial diagnostic step; if a negative reaction occurred, then SPT and IT should be applied with the same concentration of Pen G, until a positive reaction developed or all the skin testing showed negative results. SPT to BPO-HSA was safe, but its positive rate was only 47.8% in our study; it seems to be less important than skin test to Pen G. As a whole, the skin testing procedure we recommend is relatively reliable, safe and practical even in individuals extremely sensitive to penicillin. In addition, once the patient develops a positive IPT, Pen G residue on the testing site should be wiped away rapidly and washed out with cool water thoroughly to disrupt further violent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Skin tests in patients with history of anaphylactic reaction to penicillin].

Skin tests including immediate patch test (IPT), skin prick test (SPT), or intradermal test (IT) with penicillin G(PenG) and SPT with benzylpenicilloyl human serum albumin (BPO) were done in 54 patients with history of anaphylactic reaction to penicillin or shock of unknown cause. 26 patients with penicillin allergy were diagnosed. BPO specific IgE measured with ELISA gave a lower positive rate in detecting penicillin allergy as compared with the tests mentioned above. The results of skin tests in 26 patients showed that IPT with 500 IU/ml of PenG was not only accurate but also safe. Because no skin injury occurred and PenG residue could be washed out, the amount of PenG penetrated into skin is very small, thus, adverse reactions were very few. It is recommended that IPT with PenG in 500 IU/ml concentration is performed at the beginning of skin tests. If negative, SPT and then IT both with a solution of 500 IU/ml concentration are carried out, until a positive reaction occurs. This procedure is relatively accurate, simple and safe.

[A preliminary study on isolation, purification and identification of penicillium chrysogenum allergen].

Penicillium chrysogenum crude extract was prepared in our laboratory. The protein concentration of this allergen assessed by coomassie blue G250 stain was 44-48 mg/ml. Three protein bands P1, P2a and P2b, were obtained by PAGE. Molecular weights of the bands were 94,000, 43,000 and 25,000 respectively as compared with standard molecular weight markers. Gel filtration through sephadex G200 revealed two peaks. These fractions were monitored for absorbance at 280 nm and combined into 3 pools according to the results of PAGE. Tube 1(T1), T2 and T3 were obtained. The average size of wheals developing after intradermal skin testing showed that T2 induced the strongest reaction. Since the main component of T2 was P2a, it is supposed that P2a of P. chrysogenum extract contains the protein with the highest allergenicity.

[Biologic effects of hyperthermia and radiation on gastric cancer cells (SGC-7901) in vitro. II. Ultrastructural changes of cells].

Different characteristic damages of the SGC-7901 gastric adenocarcinoma cells were studied by electron microscopy 1, 36, 72, 96 and 120 hours after heating and radiation in vitro. The visible damages, such as the enlarged mitochondria, increase of lysosomes and perichromatin granules could be shown 1 hour after heating (43 degrees C for 30 min) but no visible damages of the cells were shown until 36 hours following radiation (500 rad). In order to study the ultrastructural changes of the gastric cancer cells in mitosis after heating and radiation, we have used the new method of ultrastructural research in selecting and observing the M cell in vitro and found loosened structure of chromosome and disappearance of microtubules 1 hour following hyperthermia. At the same time, no apparent abnormalities of the mitotic cells were observed after radiation. It is the chief cause of division delay in heat injured cells. However, the chromosomes and microtubules of the new mitotic cells could recover 36 hours after heating (43 degrees C for 30 min). After radiation, the giant cells and abnormal morphologic changes of cells gradually increase and the living cells decrease. Unexpectedly, the division of a few giant cells is observed 72 hours after heating and radiation.

[Biologic effects of hyperthermia and radiation on gastric cancer cells (SGC-7901) in vitro--I. Influence on cell growth curve, number of colonies and mitosis].

Biologic effects of hyperthermia (42 degrees-44 degrees C) and radiation on SGC-7901 were studied quantitatively and morphologically. Action of hyperthermia and radiation on the population and subpopulation of cells was monitored by cell growth curve and colony counts. The results show that both hyperthermia (43 degrees C for 30 min) and radiation (500 rad) can cause the cell kill and growth curve decrease but the cells still tend to proliferate. The synergistic action of heat plus radiation is demonstrated when they are given in the interval of 30 min. The thermal enhance rate was 1.27 and 1.37 for survival rate down to 2% and 5%. The concentration of potassium ions in the media is increased with cell kill after heat and radiation. The damage from heating appears like a direct kill or immediate death, the damage from radiation reveals delayed or metabolic death. Partial and transitory redistribution of cell cycle occurs following heating or radiation. Delayed division is more marked following heating than radiation. The synchronization effect may be used to hit the cycling tumor cells in the most radiosensitive phase.

Threonine kinetics at graded threonine intakes in young men.

A study was undertaken in eight healthy young men to examine the effects of varying intakes of threonine on plasma free threonine concentrations and threonine kinetics, using a 3 h constant intravenous infusion of L-[1-13C]threonine. Subjects consumed diets based on an L-amino acid mixture, in which the quality of threonine was reduced every 7 days. On the last day of each diet period, determinations of plasma threonine flux and threonine oxidation were carried out while subjects consumed small meals, each supplying 1/12 daily intake, at hourly intervals. Threonine oxidation rates fell with reduced threonine intake, reaching a relatively constant level at intakes of 20 mg.kg-1.day-1 and below. These metabolic data are discussed in relation to the currently established value of 7 mg.kg-1.day-1 as the upper range of the threonine requirement for healthy young adults. It is concluded that actual threonine requirements may be considerably higher for this age group.

Lysine kinetics at graded lysine intakes in young men.

Healthy young men participated in a study designed to explore the effects of decreasing dietary lysine content on plasma amino acid concentrations and lysine kinetics, studied with L-[1-13C]lysine as tracer. Diets provided adequate energy and the equivalent (N X 6.25) of 0.8 g protein kg-1.day-1 as a synthetic L-amino acid mixture simulating egg protein. Lysine intake was reduced every 7 days. Changes in plasma amino acids suggested that effects characteristic of a dietary lysine inadequacy were prevented by consuming more than 32 mg lysine.kg-1 day-1. Primed, continuous intravenous infusions of L-[1-13C]lysine, at the end of each diet period while subjects were in the fed state, showed that as dietary lysine was reduced, 13C enrichment increased in plasma lysine and decreased in expired CO2. It was estimated that lysine oxidation exceeded, by 4.4 mg kg-1 day-1, the lysine intake of 20 mg kg-1.day-1 indicating that the lysine required for body protein maintenance would probably exceed this latter value. These results are discussed in relation to the physiological requirement in adults for lysine, currently accepted to be met by an intake of 12 mg kg-1.day-1. which is assumed to be the upper range of the lysine requirement for this population group.

Response of alanine metabolism in humans to manipulation of dietary protein and energy intakes.

Healthy young adult men were studied with 3 different series of dietary regimens: different levels of protein intake ranging from 1.5 to 0.0 g . kg-1 . day-1; different levels of dietary energy intake; and an excessive intake of protein (3.9 g . kg-1 . day-1). Under each dietary condition, subjects were infused postabsorptively with L-[1-13C]leucine, L-[15N]alanine, and L-[3,3,3-2H3]alanine to measure leucine and alanine kinetics. Leucine flux was significantly reduced when protein intake was restricted (maximum reduction = 24%), but changed insignificantly with dietary energy change or excessive protein intake. Alanine flux and de novo synthesis increased significantly when protein intake was restricted (maximum increase = 50%), changed proportionally with changes in dietary energy, and was significantly reduced with high protein intake. Stepwise regression showed that dietary carbohydrate intake, not protein intake, was the primary factor affecting alanine de novo synthesis. In addition, the alanine 2H tracer produced a 2.5-fold greater measure of alanine de novo synthesis than did the alanine 15N tracer.

Quantitative aspects of glycine and alanine nitrogen metabolism in postabsorptive young men: effects of level of nitrogen and dispensable amino acid intake.

The nutritionally indispensable amino acids (IAA) alone do not maintain body nitrogen (N) balance; a source of "nonspecific" nitrogen from dispensable amino acids (DAA), such as from glycine and alanine or other N compounds, is required. However, the in vivo regulation of the metabolism of these amino acids in humans with varying nutritional states has received little study. Hence, the effects of N intake and the IAA:DAA ratio on kinetic aspects of whole-body alanine and glycine metabolism were examined in eight healthy young adult male subjects. They received an L-amino acid diet supplying N equivalent to about 1.5 g and 0.6 g protein (N X 6.25) per kilogram body weight per day. All were studies at each N level with the IAA:DAA ratio (wt/wt) of 1:1 and 1:0, each for a 7-d diet period. Constant primed, intravenous infusions of L-[1-13C]leucine together with either L-[15N]alanine (four subjects) or [15N]glycine (four subjects) were given to each subject at the end of the diet period, after an overnight fast, to determine rates of de novo whole-body alanine and glycine N synthesis. The rate of alanine synthesis was similar (P greater than 0.05) for all four diets. Glycine de novo N synthesis declined (P less than 0.01) with removal of dietary DAA, especially at the lower intake, where the mean rates [micromoles/(kilogram X hour)] were 59 and 20 for 1:1 and 1:0 ratios, respectively. The possible significance of reduced rates of glycine N synthesis for maintenance of protein nutritional status in the healthy adult is discussed.