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At least 811 records · Page 45Linked to original sources

Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes.

AIM: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 % of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drug-drug interaction. METHODS: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery. Primary incubated hepatocytes were treated with 0, 0.01, 0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis. RESULTS: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1 mM) showed no inhibitory effect on the cellular protein expression of P450 3A4. CONCLUSION: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression. propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.

Aryl Hydrocarbon Hydroxylases↗

[Atherosclerosis and androgen levels in elderly males].

OBJECTIVE: To observe the relation of androgen levels and atherosclerosis (AS) in elderly males. METHODS: Both carotid arteries and arteries of lower extremity were examined with Doppler ultrasonography. Those with arteriosclerosis and much atheromatous plaque were designated as case group, and those with normal results formed control group. Total testosterone (TT), free testosterone (FT) and estradiol (E2) were measure by radioimmunoassay, HDL-C, LDL-C, TC and TG were assayed by colorimetry, vascular endothelium growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1) were determined by ELISA. RESULT: FT was significantly lower in case group than in control group (P<0.01), no differences were found in TT, E2. HDL-C in control group was higher than that in case group (P<0.01), TC and TG were higher in case group than those in control group (P<0.05). HDL-C was correlated positively and LDL-C was negatively with FT level, while both TC and TG in case group had negative relation with FT. VEGF was higher in case group (P<0.05), and it had negative relation with FT in both groups. TNF-alpha and IL-6 were significantly higher in case group (P<0.05), and they had negative relation with FT. sICAM-1 was significantly lower in control group than it in case group (P<0.01). CONCLUSION: The normal androgen levels, especially FT, have beneficial effect in AS development in elderly males. Low FT level may be an independent risk factor in AS development.

Aged↗

Development and evaluation of field methods for ammonia in air.

Three methods for measuring ammonia in air have been evaluated. Filters impregnated with 10% (volume/volume) phosphoric acid in methanol were used for two methods. Sampling was done either with a filter cassette connected to a pump or with the filters placed in a passive monitor (Gasbadge). The filters were leached with distilled water after the sampling and analyzed with ion chromatography or colorimetry (Nessler). The third method tested was a colorimetric air-monitoring badge system (ProTek). The tests showed that the accuracy of the filter methods is good and that the results are not affected by humidity. If ion chromatography is used for the analysis, amines do not interfere. The Gasbadge monitors increased their uptake when the air velocity over the sampler was raised from 0.2 to 1.0 m/s. The accuracy of the ProTek method was poor, the method was biased, and blank samples showed high values. In field tests carried out in a foundry and at a fertilizer plant, the agreement between the filter methods was good, whereas the results of the ProTek method deviated drastically from those of the other methods.

Air Pollutants, Occupational↗

Effect of sodium glycyrrhetinate on chemical peritonitis in rats.

AIM: To study the anti-inflammatory mechanisms of sodium glycyrrhetinate (SG). METHODS: Rat chemical peritonitis was used. The protein content and prostaglandin E2 (PGE2) content in exudate were measured by Folin-phenol assay and RIA, respectively. SOD activity in neutrophils (Neu) was determined by pyrogallol-NBT colorimetry. cAMP content in Neu was detected by competitive protein binding assay. RESULTS: In peritonitis caused by histamine, SG 10-20 mg.kg-1 i.m. reduced exudate volume and Neu counts, and 5-20 mg.kg-1 i.m. lowered the protein content in exudate. In peritonitis induced by carrageenan, SG 20 mg.kg-1 i.m. reduced exudate volume, Neu counts, protein content and PGE2 content in exudate, increased SOD activity in Neu, but did not affect beta-glucuronidase release from Neu. In peritonitis induced by arachidonic acid, SG 20 mg.kg-1 i.m. reduced Neu counts, protein content, and PGE2 content in exudate, and attenuated the reduction of cAMP level in Neu. CONCLUSION: SG exerts its anti-inflammatory action by lowering permeability of capillaries in inflammatory site, inhibiting Neu emigration and PGE2 biosynthesis, and scavenging oxygen free radicals.

Animals↗

[External quality control of the laboratory determination of glucose in the urine and material for its realization].

Urine of diabetics without concomitant diseases with a certain concentration of glucose was collected for preparing reference material. Water saturated with phenol (872 mmole/liter) was added to urine pool during intensive stirring on a magnetic stirrer at 20 degrees C, so that the final concentration of phenol were 50 mmole/liter. Glucose content in the resultant reference material remained stable for 130 days at 18-20 degrees C. For glucose measurements, 2 ml reference material and 0.5 ml 2.5 M sodium oxide hydrate are put in centrifuge tubes, stirred, put on boiling water bath for 2 min, cooled, and colorimetried in cuvettes with 1-mm optic route. The content of monosaccharide is calculated using the proportion rule in comparison with the values for 139 mM reference glucose solution in control urine.

Diabetes Mellitus↗

[Concentration of magnesium in serum and cerebrospinal fluid in patients with stroke].

Magnesium concentration in blood serum and cerebrospinal fluid (CSF) was determined in 131 patients aged from 21 to 91 years, with RIND, complete stroke, cerebral haemorrhage and control group. Magnesium was estimated by the use of colorimetry and the method of Mann and Yoe. The results are presented in figures. Statistical evaluations revealed significant decrease of magnesium concentrations in blood serum and CSF in ischaemic stroke compared with control group. In complete stroke significantly lower concentrations of magnesium in blood serum and CSF were found compared with RIND. In ischaemic stroke higher MgSER/MgCSF index was found compared with control group. Magnesium concentration in blood serum was not statistically different within 2 weeks of the disease. No relationships were found between blood serum or CSF Mg concentrations and gender or age.

Adult↗

[Transduction of the IL-2 gene into human gastric cancer cell: an experimental study].

We evaluated the possibility of inducing a productive transfer of the IL-2 gene into human gastic cancer cells (GCC) and assessed the phenotypic and proliferative changes generated in the nude mice. The plasmid vector (BMGNeo-IL-2) carrying the human IL-2 gene was used to transduce the SGC-7901 GCC line by the lipofectin reagent. The IL-2 gene was analyzed by Southern blot and productive IL-2 release using IL-2-dependent CTLL. Cytotoxicity of LAK cells was tested by MTT colorimetry. The kinetics of in vitro growth and proliferation of parental and engineered cells were also measured. Parental and IL-2 gene transduced GCC were injected into nude mice. The tumorigenic potential of IL-2 gene-transfected GCC was evaluated by examining their in vivo growth in nude mice. The productive insertion of the IL-2 gene was achieved in SGC-7901. The amounts of IL-2 constitutively released by the engineered neoplastic cells ranged from 20 to 131 U/ml of IL-2 produced from 10(6) cells in 24 hours. Transduction of GCC with IL-2 gene did not modify the morphology and growth rate. IL-2 gene transfected cells demonstrated increased susceptibility to cell killing by LAK cells. IL-2 producing cells lost their tumorigenicity as evidenced by failure to grow in nude mice. The results demonstrate that IL-2 gene can be productively transduced into human gastric cancer cells without modifying their morphology and growth rate and this transduction leads to reduced or abrogated in vivo tumorigenic potential.

Animals↗

[Studies on effects of cytokine released from alveolar macrophage induced by mineral dust on lung fibroblast].

OBJECTIVE: To understand the role of cytokine released from alveolar macrophage (AM) in lung fibrosis caused by mineral dust. METHODS: Rabbit's AM obtained by lavage was cultured with mineral dust in vitro. Activities of tumor necrosis factor (TNF) and interleukin 6 (IL-6) in its supernatant were determined with isotope labelling method and MTT colorimetry, respectively. Human fetal lung fibroblast WI-138 was cultured with this supernatant. Proliferation of fibroblast and synthesis of collagen were examined by 3H-thymidine (3H-TdR) and 14C-proline (14C-Pro) incorporation and its total hydroxyproline (HOP) level was analyzed by chloramine-T method. RESULTS: Proliferation of lung fibroblast and synthesis of collagen could be enhanced by the supernatant containing AM induced by quartz, asbestos and uranium mineral dust, with 3H-TdR incorporated counts per minute (cpm) of 6,584, 3,848 and 6,893 in the group of 100 micrograms 3H-TdR and 14C-Pro incorporated 27,952, 13,416 and 18,538 in the group of 200 micrograms respectively, which were significantly higher than those in the control group. Total HOP levels in the culture media for lung fibroblast enhanced by AM supernatant were 22.41, 24.00 and 21.39 micrograms/ml, respectively, and was significantly higher than that in the control group (12.91 micrograms/ml). Release of TNF and IL-6 could be stimulated by mineral dust, such as quartz, asbestos and uranium mineral dust, and their activities were significantly higher than those in the control group, with those of 1,396, 1,198 and 852 U/ml in TNF group and 1,336, 1511 and 1,335 U/ml in IL-6 group, respectively. Proliferation of lung fibroblast and synthesis of collagen could be inhibited by antibody against TNF and interferon-r (gamma), and the effect of the latter was weaker than that of the former on inhibition of fibroblast proliferation and the effect on collagen synthesis was just in the opposite direction. CONCLUSION: Lung fibrosis caused by mineral dust correlated with abnormal expression of TNF and IL-6. Antibody against TNF and gamma interferon could antagonize the effect of NTF and IL-6.

Animals↗

[Differentiation of lens epithelial cell and effects of serum and ocular tissue on its proliferation in vitro].

OBJECTIVE: To study the pathogenesis of lens posterior capsular opacification (PCO) and the effects of the breakdown of blood-aqueous barrier and remain of lens cortex on PCO in cell culture level. METHODS: The differentiation of cultured bovine lens epithelial cells (BLEC) was observed by Coomassie BB staining, light and electron microscope. The effects of fetal bovine serum, aqueous humor and lens cortex, etc., on the proliferation of BLEC were tested by Giemsa-staining colorimetry. RESULTS: BLEC in vitro could gradually differentiate into lens fiber cells or lens fibers in 1-7 passages. The characteristics of differentiation were that the shape of cells changed from polygon into fusiform and fibriform, the bulk enlarged, and cytoskeleton gradually increased. Fetal bovine serum promoted the proliferation of BLEC depending on its concentration (P < 0.05). High concentration of aqueous humor inhibited the proliferation (P < 0.01). Supernatant and suspension of lens cortex, supernatant of lens nucleus, vitreous humor could promote the proliferation (P < 0.01). CONCLUSION: The differentiation of lens epithelial cells plays important roles in PCO, the breakdown of blood-aqueous barrier, the remain of lens cortex and the prolapse of vitreous may promote PCO by stimulating the proliferation of lens epithelial cells.

Animals↗

The color of gingiva studied by visual color matching. Part I. Experimental studies on the discrimination threshold for color difference and effect of training.

As a preliminary experiment on the gingival color indicated by Munsell system, the makings or the qualities for color sensation of the individual were checked with regard to (1) discrimination threshold for color difference with certain color range of gingiva (paired difference test for color comparison) and (2) promotion of memorial power by training (test for memory color). A total of 20 males and females (20-30 years old) participated in this preliminary study as experimental subjects and the following results were obtained: (1) the average color discrimination threshold for color difference among subject trained for color memory is 0.8 Lab. (Hunter), and is assumed to be greater in the actual colorimetry of gingiva, (2) the similarity of discrimination is more frequent among the subjects trained for color memory than among those who were not trained, and (3) training for color memory is found to be effective in promoting the ability for color discrimination.

Adult↗

[Research of daunomycin as an agent for preventing posterior capsule opacification].

OBJECTIVE: To investigate the inhibitory activity and the effective concentration of daunomycin against the proliferation of lens epithelial cells in vitro, and make progress in pharmacological prevention of posterior capsule opacification. METHODS: Cultured bovine, rabbit and human lens epithelial cells were exposed to 0.5, 2.5, 5.0, 7.5 and 10.0 micrograms/ml daunomycin solution for ten minutes. Growth of cells was observed, after 48 hours of exposure, absorbency of the cells was tested by using Giemsa staining and colorimetry, and the median lethal dose (LD50) was calculated respectively. RESULTS: Daunomycin significantly suppressed the proliferation of bovine, rabbit and human lens epithelial cells in vitro, showing dose-dependent manner. Daunomycin can effectively inhibit the proliferation of human lens epithelial cells at the concentration of 0.5 microgram/ml, almost reaching the greatest effect at the concentration of 7.5 micrograms/ml. The calculated LD50 for bovine, rabbit and human lens epithelial cells was 0.49, 4.30 and 4.06 micrograms/ml respectively. CONCLUSION: Short time exposure of daunomycin at low concentration can effectively inhibit the proliferation of lens epithelial cells in vitro, after further research in vivo, daunomycin may possibly become a valuable agent for the prevention of posterior capsule opacification.

Adult↗

Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone.

BACKGROUND: In Paget disease of bone (PD), serum total alkaline phosphatase (TAP) is a valid marker of disease activity. The aim of the present longitudinal study was to compare TAP with new and potentially more specific markers of bone turnover in bisphosphonate-treated patients with PD. METHODS: Twenty patients with active PD were studied before and after treatment with 2 mg of intravenous ibandronate over a period of 12 months. TAP (by colorimetry), serum bone-specific alkaline phosphatase (BAP; by enzyme immunoassay), serum osteocalcin (OC; by ELISA), serum bone sialoprotein (BSP; by RIA), and urinary total pyridinoline (PYD; by HPLC) and deoxypyridinoline (DPD; by HPLC) were measured as markers of bone turnover. RESULTS: Before treatment, TAP, BAP, and BSP were increased in all 20 patients, whereas OC was increased in 10, PYD in 13, and DPD in 15 patients. Three months post treatment, nine patients showed normalized TAP values, and a >/=25% re-increase (i.e. , relapse) was observed in all patients after 12 months. A normalization of BAP was achieved in six patients only. No significant changes were found for OC. BSP was decreased significantly at 24 h, and DPD at 48 h post treatment. A normalization of BSP was found in 8, of PYD in 18, and of DPD in 16 cases. Both PYD and DPD increased significantly from 9 months post treatment onward. CONCLUSIONS: Most markers of bone turnover show similar long-term changes after treatment of active PD with ibandronate. With regard to cost-effectiveness and assay performance, TAP remains the marker of choice in therapeutic monitoring of PD. However, more specific markers may improve the biochemical assessment of PD in certain situations.

Aged↗

Quantitative chromatics analysis for computer imaging of cytologic subtypes of lung cancer stained by Papanicolaou stain.

OBJECTIVE: To determine the role of quantitative chromatics analysis in the classification of subtypes of lung cancer stained by Papanicolaou stain. STUDY DESIGN: By means of computer image analysis, 60 keratinized squamous carcinoma cells (KSCC), 88 nonkeratinized squamous carcinoma cells (NKSCC) and 150 adenocarcinoma cells (ACC) from lung cancer in sputum smears stained by Papanicolaou stain were analyzed and distinguished based on quantitative colorimetry. The features measured were the content of three primary colors, red (R), green (G) and blue (B) and the coefficients of R, G and B (r, g and b, respectively). Hue, saturation, brightness and gray level were also measured. A stepwise discriminant analysis was carried out. RESULTS: The values of R, G and B and r, g and b, hue and saturation in NKSCC and ACC were significantly different from those of KSCC, and the changes in the three primary colors were more sensitive than those in the gray level. Computer assessment based on three primary color coefficients, hue and saturation yielded accuracy of distinguishing KSCC from NKSCC and KSCC from ACC of 95.2% and 95%, respectively. CONCLUSION: Quantitative analyses of R, G and B and r, g, b and hue and saturation are valuable in distinguishing KSCC from NKSCC and ACC.

Adenocarcinoma↗

The potential of phosphorescence spectrometry in clinical chemistry--the new generation of instrumentation and methodology.

We review recent advances in instrumentation and methodology in phosphorimetry that should facilitate the use of phosphorimetry for clinical analyses and recent phosphorescence studies of interest to the clinical chemist. We indicate recent advances, particularly improvements in instrumentation, novel methodologies, and new chemical processes that result in either an increase in sensitivity or selectivity (or both) of measurement of compounds of clinical importance. The greatest use of phosphorimetry in the clinical laboratory will not be for the analysis of very large numbers of samples for one species via automatic instrumentation, but rather will be for the analysis of those molecular species difficult or impossible to measure by conventional methods (colorimetry, fluorometry, etc.). Although various instrumental and methodological advances are discussed separately here, the most important use of these advances in clinical chemistry will undoubtedly be when two or more of them are combined, for example, in the use of time- or frequency-resolved phosphorimetry for the selective measurement of the phosphorescence resulting with inorganic probes and the appropriate choice of solvent and pH (of course, the instrument could contain an image vidicon detector for rapid determination of the spectrum, the decay curve, or both).

Antimetabolites↗

Glucocorticoid-induced apoptotic pathways in eosinophils: comparison with glucocorticoid-sensitive leukemia cells.

Glucocorticoids are known to promote apoptosis of eosinophils, normal and neoplastic lymphoid cells, and blastic cells in some patients with acute myeloid leukemia. We investigated the biochemical signal transduction pathways, in particular, the generation of reactive oxygen species (ROS) and activation of caspases in dexamethasone (DEX)-induced apoptosis of eosinophils, and we compared them with those in DEX-sensitive myeloid and lymphoid leukemia cell lines. The GC-receptor antagonist completely abolished DEX-induced apoptosis of eosinophils and leukemia cells. Among inhibitors related to the ROS system, diphenylene iodonium (DPI), a nicotinamide adenine dinucleotide diphosphate (NADPH) oxidase inhibitor, strongly inhibited both spontaneous and DEX-induced apoptosis of eosinophils at concentrations as low as 0.2 to 2 mumol/L, while promoting apoptosis of leukemia cells in a dose-dependent manner. Apocynin, another NADPH oxidase inhibitor, and antioxidants did not affect the apoptosis of eosinophils or leukemia cells. DEX treatment did not change intracellular production of O2- and H2O2, and it decreased the extracellular release of O2- in both cells. These results suggest little or no involvement of ROS generation in DEX-induced apoptosis of both cells. Although among peptide-based caspase inhibitors, only z-VAD-FMK, a broad caspase inhibitor, partially inhibited the apoptosis of eosinophils and leukemia cells, DEX treatment increased the activities of caspases 2-, 3-, 6-, and 8-like proteases assessed by colorimetry in both cells, suggesting the involvement of a similar caspase activation pathway in DEX-induced apoptosis in both cells. DPI markedly reduced caspase 3-like activity in eosinophils, while augmenting the activity in leukemia cells, indicating that DPI acts upstream of caspase 3 activation opposingly in both cells. Thus, the action of DPI in eosinophils seems peculiar in respect to apoptosis induction, and DPI appears to exert an influence on unknown targets rather than those involved in NADPH oxidase inhibition.

Apoptosis↗

[Arterial plasma nitric oxide and lactate level in hemorrhagic shock patients].

OBJECTIVE: To investigate the relationship between arterial plasma nitric oxide(NO), lactate (LA) concentration and prognosis of hemorrhagic shock patients. METHODS: The blood levels of a NO and LA were measured with fluoropholometry and colorimetry in 48 hemorrhagic shock patients, and other 30 patients for selective surgery served as controls. RESULTS: NO level was significantly lower and LA level was significantly higher in the hemorrhagic shock group than that of the control group respectively. NO level had a negative correlation with LA level and trauma index. NO level in the patients complicated by sepsis was still lower than that of the control group. CONCLUSION: Decrease of NO level may be a main cause of disturbance of microcirculation and increase of LA. The lower the NO level, the higher the LA level, the worse the prognosis. So NO and LA level play an important role in forecasting progress of hemorrhagic shock patients.

Adolescent↗

Antagonistic effect of l-stepholidine on striatal ischemic injury in rat.

AIM: To elucidate the protection of l-stepholidine (SPD) on neuronal morphology and function against the striatal ischemic injury in rat. METHODS: The forebrain ishemia to Sprague Dawley rats was induced with four-vessel occlusion. Histological examination was performed on the dorsolateral striatum with cresylviolet stain. In striatal slices of rat as an in vitro ischemic model, the activity of calcium/calmodulin-dependent protein kinase II (CCDPK) and lactate dehydrogenase (LDH) was examined by the method of 32P-incorporation and colorimetry, respectively. RESULTS: In the SPD-treated groups, most of the neurons in the striatum kept the normal morphological appearance after 30-min ischemia followed by 6-h or 12-h reperfusion. The number of neurons was much more in SPD groups than that in vehicle group. The sparse and abnormal neurons were observed in the vehicle group. SPD attenuated the ischemic effect on the CCDPK activity in striatal slices. In addition, SPD inhibited the leakage of LDH from neurons induced by ischemia in incubated striatal slices. CONCLUSION: SPD protected striatal neurons against ischemic injury and antagonized the inhibitory action on CCDPK activity induced by ischemia. SPD reduced the leakage of LDH from striatal neurons induced by ischemia.

Animals↗

Dopamine-glutamate interaction in rat striatal slices: changes of CCDPK II, PKA, and LDH activity by receptor-mediated mechanisms.

AIM: To study the effects of dopamine (DA) and glutamate (Glu) and their receptor agonists/antagonists on Ca2+/calmodulin-dependent protein kinase II (CCDPK II), cyclic AMP-dependent protein kinase A (PKA) activities and the LDH release in rat striatal slices, and to examine the interaction between DA and Glu transmitter systems in striatum. METHODS: The activities of CCDPK II, PKA, and the release of LDH were determined with the 32P-incorporation and colorimetry respectively in rat striatal slices. RESULTS: (1) Exogenous DA, D1 receptor agonist SKF 38393 and D2 receptor agonist LY 171555 reduced CCDPK II activity in striatal slices; Glu also inhibited CCPPK II activity in a concentration-dependent manner. NMDA receptor antagonist MK-801 could antagonize the inhibitory effect of SKF 38393 and LY 171555 on the CCDPK II activity. D1 and D2 receptor antagonists SCH 23390 and spiperone could also antagonize the decrease of CCDPK II activity induced by Glu; (2) DA and SKF 38393 markedly increased PKA activity in striatal slices, which was reduced by MK-801; (3) DA and Glu increased the release of LDH from the striatal neurons in a concentration-dependent manner. MK-801 antagonized the increase of LDH induced by DA. Spiperone, rather than SCH 23390, could reduce the release of LDH from striatal neuron in the presence of Glu. CONCLUSION: The interaction between DA and Glu transmitter systems is found in the regulation of the CCDPK II and PKA activities and cell function in the striatum.

Animals↗