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Biomedical subjects

Z Fang

Publications and source records attributed to Z Fang.

At least 127 records · Page 7Linked to original sources
PubMed1998

Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia.

OBJECTIVE: To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects. METHOD: As2O3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas-phase chromatography. RESULTS: The plasma maximal concentration (Cpmax) was 0.94 +/- 0.37 mg/L (x +/- s), time to peak concentration (Tp) was 4 hours, plasma distribution half-time (t1/2 alpha) and elimination half-time (t1/2 beta) were 0.89 +/- 0.29 hours and 12.13 +/- 3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83 +/- 0.45 L, system clearance (CLs) was 1.43 +/- 0.17 L/h, and area under curve (AUC) was 7.25 +/- 0.97 mg.h/L. The continuous administration of As2O3 did not alter its pharmacokinetic behaviors. During As2O3 treatment, 24-hour arsenic content in urine accounted for 1%-8% of the daily dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven-fold higher than that of pre-treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ-impairment was found. CONCLUSION: As2O3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.

Adolescent↗
PubMed1998

[Therapeutic effect of Shengmai injection on respiratory function in chronic obstructive pulmonary disease].

OBJECTIVE: To explore the therapeutic effect of Shengmai injection (SMI) on respiratory function in chronic obstructive pulmonary disease (COPD). METHODS: Twenty patients with COPD were continuously treated with SMI by intravenous drip in 14 days and examined the lung vital capacity (VC), forced vital capacity (FVC), forced vital capacity of the first second (FEV1), FEV1/FVC, maximum voluntary ventilation (MVV), maximum inspiratory pressure (MIP), load respiratory time (LT), 6 minute walk distance (6 MWD), arterial blood gas analysis, and Brog dyspnea scale before and after treatment respectively and compared with itself or control group. RESULTS: After treatment all parameters of the treatment group were better than those of control group or itself before treatment except for FVC and FEV1/FVC. There were significant difference (P < 0.05). CONCLUSION: SMI can improve respiratory function in COPD. So it is an effective rehabilitative measure in treating COPD.

Aged↗
PubMed1998

[Primitive neuroectodermal tumor of bone and soft tissue].

OBJECTIVE: To study the pathological characteristics of primitive neuroectodermal tumor (PNET) of bone and soft tissue. METHOD: Five patients with bone and soft tissue of PNET (2 men and 3 women) were studied by light microscope and immunohistochemistry. The age of the patients was 18, 18, 43, 14, 32 years and the primary sites of involvement were the ilium (n = 2), axillary fossa (n = 1), condyle of femur (n = 1), and diploe (n = 1). X-ray films showed bone osteolytic destruction, and no periosteal reaction or calcification. Surgery was performed in the patients. RESULT: All patients received combined chemotherapy and 3 received radiotherapy. Three patients died of metastatic tumor of lung 20, 13, and 5 months after invasion. 1 patient metastatic tumor of lung 20 months after invasion, and 1 patient bone extensive metastasis 1.5 months after surgery. CONCLUSION: The treatment of PNET of bone and soft tissue awaits further study.

Adolescent↗
PubMed1997

Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.

Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Asn382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.

Animals↗
PubMed1997

Modified Evans blue fluorimetry for determination of pulmonary vascular permeability in rats sustaining burns, and delayed fluid resuscitation of burn shock.

The present experiment used modified Evans blue fluorimetry to determine changes in pulmonary vascular permeability using a delayed resuscitation model of burn shock in rats. The results showed that pulmonary vascular permeability in the immediate resuscitation (IR) group regressed to normal 12-24 h following the burn whereas it regressed slowly in the delayed resuscitation (DR) group. The study showed that Evans blue fluorimetry is a reliable and sensitive method for determining pulmonary vascular permeability, and dimethyl formamide is a preferable extracting solution which provides a quick and convenient means for scientific research.

Animals↗
PubMed1997

Environmental and occupational determinants of blood pressure in rural communities in China.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Adolescent↗
PubMed1997

Enhanced choline acetyltransferase activity does not explain the action of inhaled convulsants.

Enhancement of choline acetyltransferase (ChAT) activity and increased intraneuronal acetylcholine (ACh) may explain the convulsant activity of some inhaled compounds. Enflurane, for example, enhances such activity. Accordingly, we measured choline acetyltransferase (ChAT) activity in rat cortical synaptosomes in the presence of two inhaled convulsants, flurothyl (CF3CH2OCH2CF3) and 1,2-dichlorohexafluorocyclobutane at partial pressures below and greatly exceeding those which produce convulsions in vivo. Neither agent changed the kinetic parameters, maximum velocity (vmax) or Michaelis constant (Km). The vmax for controls in the flurothyl series was 016 (0.06) nmol mg-1 min-1 and the Km was 0.23 (0.11) mmol litre-1. For the 1,2-dichlorohexafluorocyclobutane series of experiments the results for the controls were vmax 0.23 (0.10) nmol mg-1 min-1 and Km 0.20 (0.08) mmol litre-1. Modification of ChAT activity did not contribute to the excitatory effects of these agents.

Administration, Inhalation↗
PubMed1997

Two novel gene orders and the role of light-strand replication in rearrangement of the vertebrate mitochondrial genome.

Two novel mitochondrial gene arrangements are identified in an agamid lizard and a ranid frog. Statistical tests incorporating phylogeny indicate a link between novel vertebrate mitochondrial gene orders and movement of the origin of light-strand replication. A mechanism involving errors in light-strand replication and tandem duplication of genes is proposed for rearrangement of vertebrate mitochondrial genes. A second mechanism involving small direct repeats also is identified. These mechanisms implicate gene order as a reliable phylogenetic character. Shifts in gene order define major lineages without evidence of parallelism or reversal. The loss of the origin of light-strand replication from its typical vertebrate position evolves in parallel and, therefore, is a less reliable phylogenetic character. Gene junctions also evolve in parallel. Sequencing across multigenic regions, in particular transfer RNA genes, should be a major focus of future systematic studies to locate novel gene orders and to provide a better understanding of the evolution of the vertebrate mitochondrial genome.

Amino Acid Sequence↗
PubMed1997

Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers.

Present package labeling for sevoflurane recommends the use of fresh gas flow rates of 2 L/min or more when delivering anesthesia with sevoflurane. This recommendation resulted from a concern about the potential nephrotoxicity of a degradation product of sevoflurane, "Compound A," produced by the action of carbon dioxide absorbents on sevoflurane. To assess the adequacy of this recommendation, we compared the nephrotoxicity of 8 h of 1.25 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 10) versus desflurane (n = 9) in fluid-restricted (i.e., nothing by mouth overnight) volunteers when the anesthetic was given in a standard circle absorber anesthetic system at 2 L/min. Subjects were tested for markers of renal injury (urinary albumin, glucose, alpha-glutathione-S-transferase [GST], and pi-GST; and serum creatinine and blood urea nitrogen [BUN]) before and 1, 2, 3, and/or 5-7 days after anesthesia. Desflurane did not produce renal injury. Rebreathing of sevoflurane produced average inspired concentrations of Compound A of 41 +/- 3 ppm (mean +/- SD). Sevoflurane was associated with transient injury to: 1) the glomerulus, as revealed by postanesthetic albuminuria; 2) the proximal tubule, as revealed by postanesthetic glucosuria and increased urinary alpha-GST; and 3) the distal tubule, as revealed by postanesthetic increased urinary pi-GST. These effects varied greatly (e.g., on postanesthesia Day 3, the 24-h albumin excretion was < 0.03 g (normal) for one volunteer; 0.03-1 g for five others; 1-2 g for two others; 2.1 g for one volunteer; and 4.4 g for another volunteer). Neither anesthetic affected serum creatinine or BUN, nor changed the ability of the kidney to concentrate urine in response to vasopressin, 5 U/70 kg subcutaneously (i.e., these measures failed to reveal the injury produced). In addition, sevoflurane, but not desflurane, caused small postanesthetic increases in serum alanine aminotransferase (ALT), suggesting mild, transient hepatic injury.

Adult↗
PubMed1997

Convulsant activity of nonanesthetic gas combinations.

Most nonanesthetics (inhaled compounds that neither cause anesthesia when given alone nor decrease the partial pressure of a known inhaled anesthetic required to produce anesthesia) and transitional compounds (inhaled compounds that are less potent than would be predicted by the Meyer-Overton hypothesis) cause convulsions. A possible exception is the perfluoroalkane series of nonanesthetics. The present study tested whether perfluoroalkanes do provide an exception. Further, we tested whether the convulsant effects of nonanesthetic and transitional compounds were additive. The nonanesthetic perfluoropropane caused convulsions at 7.5 +/- 0.7 atm (mean +/- SD). Convulsions also were produced by perfluorocyclobutane (0.976 +/- 0.002 atm), 1,2-dichlorotetrafluoroethane (0.358 +/- 0.011 atm), 2,3-dichlorooctafluorobutane (0.085 +/- 0.007 atm), 1,2-dichlorohexafluorocyclobutane (0.055 +/- 0.007 atm), and flurothyl (0.00156 +/- 0.00039 atm). Of these, 1,2-dichlorotetrafluoroethane is a transitional compound, the remainder being nonanesthetics. The combination of flurothyl plus 1,2-dichlorohexafluorocyclobutane gave evidence of antagonism (a 17% +/- 21% deviation from additivity; P < 0.05), whereas the combination of 1,2-dichlorotetrafluoroethane plus 2,3-dichlorooctafluorobutane gave evidence of synergy (a -13% +/- 8% deviation from additivity; P < 0.05). The combinations of perfluoropropane plus perfluorocyclobutane (-4% +/- 15%), and perfluoropropane plus 1,2-dichlorohexafluorocyclobutane (-1% +/- 26%) did not produce results that deviated significantly from additivity. We conclude that pairs of these compounds either produce convulsions in an additive manner, a finding consistent with (but not proving) a common mode of action; or deviate modestly from additivity, a finding suggesting that at least a portion of the mechanistic basis for convulsions might differ, particularly for flurothyl plus other nonanesthetics, or for the combination of non-anesthetics and transitional compounds.

Animals↗
PubMed1997

Maturation decreases ethanol minimum alveolar anesthetic concentration (MAC) more than desflurane MAC in rats.

The potency of conventional inhaled anesthetics increases with increasing age: the 50% effective dose (minimum alveolar anesthetic concentration [MAC]) for anesthesia in the neonatal animal or human exceeds MAC in the young adult by approximately 30% to 60%. We tested whether this relationship also applies to the alkanols, using ethanol as a representative alkanol. We found that the MAC of ethanol in neonatal rats was 1.86 times (86% greater than) the MAC for adult rats, based on ethanol partial pressures determined from brain specimens. In contrast, the MAC of desflurane in neonatal rats was 1.19 times (19% greater than) the MAC for adult rats, less than one-fourth the 86% found for ethanol. These differences must be explained by any unitary theory of narcosis. Alternatively, the mechanistic basis for alkanol versus conventional inhaled anesthetics may differ in part or whole.

Age Factors↗
PubMed1997

Anesthetic potencies of n-alkanols: results of additivity and solubility studies suggest a mechanism of action similar to that for conventional inhaled anesthetics.

The mechanism by which n-alkanols produce anesthesia and the characteristics relevant to those mechanisms (e.g., lipid solubilities versus potencies) remain unknown. Accordingly, we determined potencies (minimum alveolar anesthetic concentration [MAC]) and solubilities of normal methanol, ethanol, butanol, hexanol, and octanol. We also determined the additivity of these alkanols with a conventional anesthetic (desflurane) and the additivity of methanol with butanol. Finally, we determined whether alkanol metabolism influences alkanol potencies. MAC for methanol, ethanol, butanol, hexanol, and octanol (0.00200, 0.000989, 0.000133, 0.0000214, and 0.00000117 atm, respectively) increased with an increasing solubility in olive oil (olive oil/gas partition coefficients 48.6, 108, 1,650, 11,600, and 93,500, respectively) and octanol (octanol/gas partition coefficients 163, 1,150, 22,900, 135,000, and 4,140,000) to give a product of MAC x solubility for olive oil approximately 10 times less (values of 0.10-0.25) than that expected from the Meyer-Overton hypothesis (compared with conventional inhaled anesthetics). There was less deviation for octanol, but the results were more variable. Inhibition of methanol and butanol metabolism by 4-methylpyrazole did not alter MAC. Methanol, ethanol, butanol, hexanol, and octanol had approximately additive anesthetic effects with desflurane, with some small but statistically significant deviations both above and below additivity. In the presence of 0.5 MAC of desflurane, we needed to add 0.4-0.6 MAC of each alkanol to inhibit the movement of 50% of the rats in response to noxious stimulation. Similarly, the effects of methanol and butanol were additive (with each other). The saline/gas partition coefficient for each alkanol was high (3700, 2650, 1400, 900, and 709 for methanol through octanol), which indicates high polarity. We conclude that the potent anesthetic effects of normal alkanols may result from an affinity to both polar and nonpolar phases. Our finding of additivity of alkanols with each other is consistent with a common mechanism of action. Similarly, the finding of additivity or slight deviations from additivity for alkanols with desflurane is consistent with mechanisms of action that have much in common.

Alcohols↗
PubMed1997

Maturation decreases ethanol minimum alveolar anesthetic concentration in mice as previously demonstrated in rats: there is no species difference.

The potency of conventional inhaled anesthetics increases with maturation: the 50% effective dose (minimum alveolar anesthetic concentration [MAC]) for conventional inhaled anesthetics in the neonatal rat or human exceeds MAC in the young adult. This increase also applies to ethanol in rats tested using MAC as the measure of anesthesia. However, the converse appears to be true for studies in mice assessed with the righting reflex; that is, adult mice are six times more resistant than neonates to the effects of ethanol. These disparate findings imply that maturation in rats and mice may produce opposing changes in the quantity or sensitivity of one or more receptors that mediate the actions of anesthetics that lead to the anesthetic state. Such a finding would be important for two reasons. First, both rodents are widely used in studies of anesthetic effects, and, thus, a species-dependent divergence in anesthetic effects has immediate experimental implications. Second, confirmation of such a species difference would supply an opportunity to test which receptors might be crucial to anesthetic mechanisms. Accordingly, we investigated whether maturation decreased ethanol potency in mice, using MAC as the measure of anesthesia. Applying standard techniques, we tested MAC for ethanol in 15 CF-1 mice aged 10 days (6-8.5 g) and in 13 mice aged 77-84 days (34-39 g). MAC decreased with maturation, and the decrease was indistinguishable from that found in our previous studies of rats.

Aging↗
PubMed1997

Effects of inhaled nonimmobilizer, proconvulsant compounds on desflurane minimum alveolar anesthetic concentration in rats.

UNLABELLED: Anesthetics depress the central nervous system, whereas nonimmobilizers (previously called nonanesthetics) and transitional compounds having the same physical properties (e.g., solubility in lipid) do not produce anesthesia (nonimmobilizers) or are less potent anesthetics than might be predicted from their lipophilicity (transitional compounds). Potential explanations for the absent or decreased anesthetic effect of nonimmobilizer and transitional compounds include the theories that the nonimmobilizers are devoid of anesthetic effect and that transitional compounds have a decreased capacity to produce anesthesia; that the effects of these compounds are not apparent because the concentrations examined are too low; or that anesthesia, or lack thereof, results from a balance between depression and excitation (all nonimmobilizer and transitional compounds produce convulsions). To examine these issues further, we tested the effect of various multiples of the convulsive 50% effective dose (ED50) of three nonimmobilizers and one transitional compound on the minimum alveolar anesthetic concentration (MAC) of desflurane in rats. The nonimmobilizer 2,3-dichlorooctafluorobutane (NI-1), from 0.7 to 1.1 times its convulsive ED50, increased the MAC of desflurane by 14%-27%, but at 1.6 times its convulsive ED50 caused no change in MAC; the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (NI-2) did not change MAC at concentrations up to its convulsant ED50, but it increased MAC by 25% and 36% at 1.3 and 1.7 times its convulsant ED50, respectively. The nonimmobilizer flurothyl (NI-3) decreased the MAC of desflurane by 20% +/- 6% (mean +/- SD) at 0.5 times its convulsant ED50, but it caused no change at higher partial pressures (up to 7.8 times its convulsant ED50), and the transitional compound CF3CCl2-O-CF2Cl (T-1) significantly decreased MAC by 16% +/- 7% at 0.8 times its convulsant ED50, but the 6%-8% decreases in MAC at 0.4 and 1.6 times its convulsant ED50 were not significant. Thus, neither nonimmobilizer nor transitional compounds produced a consistent dose-related effect on the MAC of desflurane, and any changes were small. These results suggest that the excitation produced by transitional compounds or nonimmobilizers does not explain their limited ability or inability to produce anesthesia. The data are consistent with a decreased anesthetic efficacy of transitional compounds and the lack of efficacy of nonimmobilizers. IMPLICATIONS: Inhaled compounds that do not cause anesthesia (nonimmobilizers) are used to test theories of anesthetic action. Their use presumes that a trivial explanation, such as cancelling stimulatory and depressant effects, does not explain the absence of anesthesia. The present results argue against such an explanation.

Anesthetics↗
PubMed1997

Recovery and kinetic characteristics of desflurane and sevoflurane in volunteers after 8-h exposure, including kinetics of degradation products.

BACKGROUND: Desflurane and sevoflurane permit speedier changes in anesthetic partial pressures than do older halogenated anesthetics. The authors determined the kinetic characteristics of desflurane and sevoflurane and those of compound A [CH2F-O-C(=CF2)(CF3)], a nephrotoxic degradation product of sevoflurane. METHODS: Volunteers received 1.25 minimum alveolar concentration of desflurane or sevoflurane, each administered for 8 h in a fresh gas inflow of 2 l/min. Inspired (F(I)) and end-tidal (F(A)) concentrations of anesthetic and compound A were measured during administration, and F(A) relative to F(A0) (the last end-tidal concentration during administration) during elimination. The indices of recovery were also measured. RESULTS: The ratio F(I)/F(A) rapidly approached 1.0, with values greater for sevoflurane (desflurane 1.06 +/- 0.01 vs. sevoflurane 1.11 +/- 0.02, mean +/- SD). The ratio F(A)/F(I) for compound A was approximately 0.8. The F(A)/F(A0) ratio decreased slightly more rapidly with desflurane than with sevoflurane, and objective measures indicated faster recovery with desflurane: The initial response to command (14 +/- 4 min vs. 28 +/- 8 min [means +/- SD]) and orientation (19 +/- 4 vs. 33 +/- 9 min) was quicker, and recovery was faster as defined by results of the Digit Symbol Substitution, P-deletion, and Trieger tests. Desflurane produced less vomiting (1 [0.5, 3]; median [quartiles] episodes) than did sevoflurane (5 [2.5, 7.5] episodes). The F(A)/F(A0) ratio for compound A decreased within 5 min to a constant value of 0.1. CONCLUSIONS: These anesthetics have kinetics consistent with their solubilities. Sevoflurane's greater biodegradation probably increases F(I)/F(A) differences during anesthetic administration and decreases F(A)/F(A0) differences during elimination. The F(A) for compound A differs from F(I) by 20% (F(A)/F(I) = 0.8) because of substantial degradation. Recovery from anesthesia proceeds nearly twice as fast with desflurane than with sevoflurane. Differences in ventilation, or alveolar or tissue elimination, do not completely explain the slower recovery with sevoflurane.

Anesthetics, Inhalation↗
PubMed1997

A Mycobacterium tuberculosis IS6110 preferential locus (ipl) for insertion into the genome.

A 267-nucleotide Mycobacterium tuberculosis genomic sequence (ipl, the IS6110 preferential locus) which can harbor the insertion sequence IS6110 at six alternative locations has been identified in some three-quarters of the isolates tested. Only one IS6110 copy was observed at this locus in the ipl::IS6110(+)-containing isolates tested, and all insertions had the same orientation. The implications of this finding for IS6110 fingerprint typing methods is discussed in this work.

Base Sequence↗