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1.
Zhonghua Yi Xue Za Zhi ; 103(40): 3186-3192, 2023 Oct 31.
Article in Chinese | MEDLINE | ID: mdl-37879872

ABSTRACT

Objective: To investigate the oncological outcomes of active surveillance (AS) in patients showing thyroid nodules measuring≤1 cm with highly suspicious ultrasound features. Methods: A prospective single-center cohort study. A total of 534 patients with highly suspicious thyroid nodules (2015 American Thyroid Association Nodule Sonographic Patterns and Risk of Malignancy: High Suspicion) were enrolled in this study, the patients received AS at Peking Union Medical College Hospital between January 2017 and November 2022 to assess oncological outcomes (disease progression, recurrence/metastasis rate, etc). The patients were followed up every 6 months for physical examination and neck ultrasound examination. And the value of tumor volume changes in evaluating tumor enlargement was explored too. Results: There were 413 females and 121 males in this cohort, with a mean age of (42.6±11.8) years. During a median follow-up period of 45.6 months (ranged from 3.5 to 176.0 months), disease progression occurred in 26 patients (4.9%) with highly suspicious thyroid nodules, characterized by a minimum 3-mm increase in tumor diameter in 19 patients (3.6%) and lymph node metastases in 7 patients (1.3%). Forty-seven (8.8%) patients opted for delayed surgery, with 29 patients due to a change in preference. There was no significant differences in pathologic and follow-up outcomes between patients with disease progression and preference change. Patients aged≤40 years had a higher cumulative incidence of 5-year disease progression than those aged>40 years (4.9% vs 1.9%, P=0.060). No patients experienced distant metastases or deaths. Among the 595 high-risk thyroid nodules with continuous volume assessment results and an increase in nodule diameter of less than 3 mm (including all high-risk nodules in patients with single or multiple nodules), 184 (30.9%) and 79 (13.3%) nodules exhibited volume increases of more than 50% and 100%, respectively, in multiple measurements. Among the nodules with volume changes exceeding 50% and 100%, the proportion of nodules with a baseline tumor diameter of≤0.5 cm was significantly higher than those with a diameter of>0.5 cm, at 69.0% vs 31.0% (P<0.001) and 77.2% vs 22.8% (P<0.001), respectively. Conclusions: Active surveillance in patients with highly suspicious subcentimeter thyroid nodules has good short-term oncological outcomes and can be considered a safe alternative to surgery. Due to the large variability in the measurement results of tumor volume, it is not suitable as an indicator for evaluating tumor enlargement.


Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Male , Female , Humans , Adult , Middle Aged , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Cohort Studies , Prospective Studies , Watchful Waiting , Ultrasonography/methods , Retrospective Studies , Disease Progression
3.
Poult Sci ; 98(7): 2927-2932, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30753620

ABSTRACT

This experiment was conducted to evaluate the effects of lysine deficiency or excess on growth and the expression of lipid metabolism genes in slow-growing birds. A total of 360 one-day-old chicks were randomly divided into 3 groups, with 6 replicates of 20 birds each. The birds fed the basal diet with a total lysine 0.60% (LL), 1.00% (ML), or 1.40% (HL). The amount of lysine (ML) as the control group, LL and HL as the experimental group, the trial period last 3 wk. The results showed that compared with ML, LL significantly decreased average daily gain and average daily feed intake and remarkably increased feed conversion ratio of birds at 21 day old (P < 0.01), while the above indices in HL had no significant effects (P > 0.05). Besides, LL reduced the pectoral muscle rate (P < 0.01) and decreased the percentage of abdominal fat significantly (P < 0.05). In addition, compared with ML, the expression of fatty acid binding protein 1 (FABP1), acetyl-CoA carboxylase (ACC), malic enzyme (ME), and sterol regulatory element binding protein 1 (SREBP1c) mRNA of liver in LL was significantly decreased (P < 0.05), and the expression of cholesteryl ester transfer protein (CETP) mRNA was significantly increased (P < 0.01), whereas LL had no significant effects on the expression of peroxisome proliferator activated receptor alpha (PPARα) mRNA (P > 0.05). Moreover, compared with ML, HL significantly reduced the expression of FABP1, ACC, ME, SREBP-1c, and PPARα mRNA in the liver (P < 0.05), and had no significant effects on the expression of CETP mRNA (P > 0.05). The results of current research suggest that dietary lysine deficiency could reduce the growth and fat deposition of slow-growing broilers mainly by downregulating the expression of lipid synthesis genes.


Subject(s)
Diet/veterinary , Lipid Metabolism/drug effects , Lysine/pharmacology , Animal Feed/analysis , Animals , Chickens/growth & development , Gene Expression , Lipid Metabolism/genetics , Liver/drug effects , Liver/metabolism , Lysine/deficiency , Random Allocation
4.
Zhonghua Wai Ke Za Zhi ; 56(10): 768-771, 2018 Oct 01.
Article in Chinese | MEDLINE | ID: mdl-30369159

ABSTRACT

Objective: To investigate the safety and efficacy of needle-tract assisted standard percutaneous nephrolithotomy (PCNL) for the treatment of complicated upper urinary tract calculi. Methods: The clinical data of 1 562 patients with complicated upper urinary calculi who received standard PCNL from December 2013 to December 2017 at Department of Urology, the First Affiliated Hospital of Xiamen University were retrospectively analyzed. There were large residual stones in 256 patients through B-ultrasound exploration after standard PCNL, could't be detected with nephoscope in standard PCNL tracts. 16 F mini PCNL tract were established in 120 cases for treatment of residual stones, while needle-tract were established in order to guide nephroscope to find residual stones in 126 cases. Needle-tract were transferred to 16 F mini PCNL tract for treatment of residual stones in 10 patients if these residual stones could't be detected through needle-tract. Operation time, change of hemoglobin level after operation, incidence of postoperative complications, time of hospitalization and rate of stone clearance were measured in two groups. The statistical methods used included t test, Wilcoxon rank sum test, and χ2 test. Results: There were 1 to 3 mini tracts (M(QR): 1(1)) established in the mini tracts group and 1 to 7 needle-tracts (M(QR): 3(2)) established in the needle-tract group (Z=-10.57, P=0.000). Compared with mini tract group, the operation time ((62.0±18.0) minutes vs. (84.0±15.5) minutes, t=10.242, P=0.000), hospitalization time ((4.40±0.86) days vs. (5.20±0.81) days, t=7.570, P=0.049), hemoglobin dropped ((1.31±0.47) g/L vs. (2.74±0.63) g/L, t=20.12, P=0.000), and incidence of postoperative complications (7.9% (10/126) vs. 19.2% (23/120), χ2=6.674, P=0.01) of needle-tract group were lower, while postoperative stone clearance rate was higher (89.7% vs. 76.7%, χ2=7.497, P=0.006). No perioperative severe complications such as pleural injury, pneumatothorax, perforation of renal, trauma of abdominal organ occurred in two groups. Conclusion: Needle-tract assisted standard PCNL for the treatment of complicated upper urinary calculi can significantly improve stone clearance rate, reduce operation time, decrease risk of kidney and surrounding organs damage.


Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Humans , Kidney Calculi/therapy , Retrospective Studies , Treatment Outcome , Urinary Calculi
5.
Nanotechnology ; 29(46): 465202, 2018 Nov 16.
Article in English | MEDLINE | ID: mdl-30203785

ABSTRACT

Germanane, fully hydrogenated germanene, has recently attracted great interest, both theoretical and experimental. In this paper we thoroughly study strain-tunable n/p-type doping in germanane by adsorption of tetrathiafulvalene (TTF)/tetracyanoquinodimethane (TCNQ) molecules through first-principles calculations. The results show that both TTF and TCNQ molecules can non-covalently functionalize the electronic properties of germanane. Not surprisingly, TTF molecular adsorption induces n-type doping in germanane because the TTF molecule is a typical electron donor. Moreover, a linearly tunable band gap of germanane and differing n-type doping strengths can be realized by a biaxial strain ranging from -3% to 3%. Analysis indicates that tensile strain would promote the doping effect whereas compressive strain would inhibit it. Comparatively, TCNQ molecular adsorption induces a germanane/TCNQ system which exhibits metallic characteristics. Surprisingly, however, under a tensile strain of 2.5%, a strong p-type doping effect is achieved in germanene/TCNQ. In particular, with increasing tensile strain over the range 2.5%-3%, the strain-tunable p-type doping effect decreases gradually. Such a multiple effect of molecular adsorption and strain on the electronic properties of germanane could be helpful for potential future applications of germanane-based electron devices.

6.
Genet Mol Res ; 15(3)2016 Sep 02.
Article in English | MEDLINE | ID: mdl-27706699

ABSTRACT

Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs. As a key regulator of gene expression, miRNA are involved in a wide variety of biological processes; in fact, several miRNAs have been implicated in the development and progression of inflammatory or autoimmune disorders. In this study, we compared the miRNA expression profiles of dermal MSCs from patients with psoriasis to those in MSCs from normal individuals by microarray, and found that the pro-inflammatory miRNA miR-155 was significantly overexpressed in psoriatic MSCs (2.44 fold, P < 0.001). Additionally, the expression of miR-155 target gene TAB2 (8.47 ± 1.55 vs 6.38 ± 2.10, P < 0.01,) and the downstream gene iNOS (5.26 ± 2.58 vs 3.73 ± 1.89, P < 0.05) was found to be inhibited in psoriatic dermal MSCs by real-time PCR. Therefore, we speculated that the elevation in miR-155 levels may be an indicator of, or a key regulatory pathway in, the pathogenesis of psoriasis, resulting in functionally impaired dermal MSCs.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Dermis/metabolism , Gene Expression Regulation , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , Psoriasis/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adult , Case-Control Studies , Dermis/pathology , Female , Humans , Male , Mesenchymal Stem Cells/pathology , MicroRNAs/metabolism , Middle Aged , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oligonucleotide Array Sequence Analysis , Psoriasis/metabolism , Psoriasis/pathology , Real-Time Polymerase Chain Reaction , Severity of Illness Index , Signal Transduction
7.
Phys Chem Chem Phys ; 18(33): 22794-8, 2016 Aug 17.
Article in English | MEDLINE | ID: mdl-27498822

ABSTRACT

Rod-like copper manganese mixed oxides (CuMnx-NR) have been synthesized from copper manganese mixed oxide particles by sodium hydroxide hydrothermal treatment, and a higher BET surface area of 221 m(2) g(-1) is obtained on the nanorod-like sample, which exhibits superior catalytic activity toward toluene combustion at 210 °C due to the increase in its oxygen mobility of the chemisorbed oxygen species as well as the increase in surface concentrations of higher valance cations, Cu(2+), Mn(3+) and Mn(4+), in the samples.

8.
Genet Mol Res ; 14(4): 15793-801, 2015 Dec 02.
Article in English | MEDLINE | ID: mdl-26634547

ABSTRACT

Psoriasis is a common chronic relapsing inflammatory skin disease, in which mesenchymal stem cells (MSCs) have been hypothesized to play an important role in abnormal localized inflammation and vascular proliferation observed in skin lesions. Previous studies have revealed abnormal gene expression patterns, DNA methylation status, and cytokine secretion of MSCs in psoriatic skin lesions, as well as some gene expression abnormalities related to inflammation and angiogenesis. We further verified the gene and protein expressions of inflammation-related lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), and angiogenesis-related hematopoietically expressed homeobox (HHEX) in MSCs derived from the skin lesions of psoriasis patients. The gene expression of LITAF, DUSP1, and HHEX in dermal MSCs was measured at the mRNA level using reverse transcription-polymerase chain reaction and the corresponding protein expression levels were analyzed by western blotting analysis. The gene and protein expression levels of LITAF, HHEX, and DUSP1 in dermal MSCs were significantly lower in psoriasis patients compared to controls. Amplification and western blotting results were consistent with our previously reported gene chip data. Our results suggest that dermal MSCs in psoriatic skin lesions may be involved in the development, progression, and regulation of localized inflammatory abnormalities by reducing the expression of LITAF, HHEX, and DUSP1, which are related to inflammation and angiogenesis.


Subject(s)
Dual Specificity Phosphatase 1/genetics , Gene Expression , Homeodomain Proteins/genetics , Mesenchymal Stem Cells/metabolism , Nuclear Proteins/genetics , Psoriasis/genetics , Transcription Factors/genetics , Adult , Case-Control Studies , Dual Specificity Phosphatase 1/metabolism , Female , Homeodomain Proteins/metabolism , Humans , Male , Middle Aged , Nuclear Proteins/metabolism , Psoriasis/diagnosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Severity of Illness Index , Transcription Factors/metabolism , Young Adult
9.
J Biol Regul Homeost Agents ; 29(3): 521-6, 2015.
Article in English | MEDLINE | ID: mdl-26403390

ABSTRACT

With the development of photoelectric technology and single-chip microcomputer technology, objective optometry, also known as automatic optometry, is becoming precise. This paper proposed a presbyopia optometry method based on diopter regulation and Charge Couple Device (CCD) imaging technology and, in the meantime, designed a light path that could measure the system. This method projects a test figure to the eye ground and then the reflected image from the eye ground is detected by CCD. The image is then automatically identified by computer and the far point and near point diopters are determined to calculate lens parameter. This is a fully automatic objective optometry method which eliminates subjective factors of the tested subject. Furthermore, it can acquire the lens parameter of presbyopia accurately and quickly and can be used to measure the lens parameter of hyperopia, myopia and astigmatism.


Subject(s)
Diagnostic Imaging , Eye , Microcomputers , Optometry , Presbyopia , Diagnostic Imaging/instrumentation , Diagnostic Imaging/methods , Eye/pathology , Eye/physiopathology , Humans , Optometry/instrumentation , Optometry/methods , Presbyopia/diagnosis , Presbyopia/physiopathology
10.
Genet Mol Res ; 14(2): 4939-48, 2015 May 11.
Article in English | MEDLINE | ID: mdl-25966269

ABSTRACT

Bacillus pumilus is able to secrete subtilisin-like prote-ases, one of which has been purified and characterized biochemically, demonstrating great potential for use in industrial applications. In the current study, the biosynthesis and transcription of extracellular pro-teases in B. pumilus (BA06) under salt stress were investigated using various methods, including a proteolytic assay, zymogram analysis, and real-time PCR. Our results showed that total extracellular proteolytic activity, both in fermentation broth and on milk-containing agar plates, was considerably repressed by salt in a dosage-dependent manner. As Bacillus species usually secret multiple extracellular proteases, a vari-ety of individual extracellular protease encoding genes were selected for real-time PCR analysis. It was shown that proteases encoded by the aprE and aprX genes were the major proteases in the fermentation broth in terms of their transcripts in B. pumilus. Further, transcription of aprE, aprX, and epr genes was indeed repressed by salt stress. In con-trast, transcription of other genes (e.g., vpr and wprA) was not repressed or significantly affected by the salt. Conclusively, salt stress represses total extracellular proteolytic activity in B. pumilus, which can largely be ascribed to suppression of the major protease-encoding genes (aprE, aprX) at the transcriptional level. In contrast, transcription of other pro-tease-encoding genes (e.g., vpr, wprA) was not repressed by salt stress.


Subject(s)
Bacillus/enzymology , Endopeptidases/biosynthesis , Stress, Physiological/drug effects , Bacillus/drug effects , Endopeptidases/genetics , Fermentation , Gene Expression Regulation, Bacterial/drug effects , Sodium Chloride/pharmacology
11.
Genet Mol Res ; 14(1): 474-82, 2015 Jan 23.
Article in English | MEDLINE | ID: mdl-25729981

ABSTRACT

There are significant differences on the biological characteristics of bone marrow mesenchymal stem cells (BMMSCs), immunological response, and antigen-presenting functions between patients with psoriasis and normal subjects, but there are no significant differences in aborted fetuses. We examined the differences in BMMSCs between aborted fetuses and patients with psoriasis in this study. Bone marrow from normal subjects, aborted fetuses, and patients with psoriasis were obtained using a MidiMACS machine. Density gradient centrifugation method was used to isolate the bone marrow mononuclear cells of patients with psoriasis and aborted fetus and the cells were cultivated. Bone marrow CD34(+) cells from normal subjects were isolated. MTT colorimetric detection was used to test the proliferation activity of bone marrow CD34(+) cells. The purity of bone marrow CD34(+) cells and BMMSCs was determined by flow cytometry. The BMMSC culture supernatant fluid of patients with psoriasis and aborted fetuses showed no statistically significant difference with bone marrow CD34(+) cell proliferation in normal subjects (P > 0.05).


Subject(s)
Antigens, CD34/metabolism , Bone Marrow Cells/cytology , Mesenchymal Stem Cells/cytology , Adult , Cell Proliferation , Cell Separation , Cells, Cultured , Female , Flow Cytometry , Humans , Male , Middle Aged , Psoriasis/pathology , Young Adult
12.
Genet Mol Res ; 14(4): 17758-67, 2015 Dec 22.
Article in English | MEDLINE | ID: mdl-26782421

ABSTRACT

Psoriasis is an inflammatory skin disease characterized by excessive proliferation and abnormal differentiation and apoptosis of keratinocytes (KCs). Mesenchymal stem cells (MSCs) from skin lesions of psoriasis patients demonstrate abnormal cytokine secretion, which may affect KC proliferation and apoptosis. Here, we explored how MSCs from skin lesions of psoriasis patients affect HaCaT cell proliferation and apoptosis. First, flow cytometry and multipotent differentiation methods were used to identify skin MSCs, which were then co-cultured with HaCaT cells. HaCaT cell proliferation was analyzed in real-time, and cell cycle progression and apoptosis were assessed by flow cytometry. Cell morphologies and multipotencies of skin MSCs were similar between the psoriasis group and healthy control group, with high levels of CD29, CD44, CD73, CD90, and CD105 and limited expression of CD34, CD45, and HLA-DR. MSCs from skin lesions of psoriasis patients promote KC proliferation more potently and are less capable of inducing KC apoptosis. This may underlie KC proliferation and abnormal apoptosis in psoriasis skin lesions, which results in abnormal thickening of the epidermis.


Subject(s)
Keratinocytes/pathology , Mesenchymal Stem Cells/pathology , Psoriasis/genetics , Skin/pathology , Adult , Antigens, CD/biosynthesis , Antigens, CD/genetics , Apoptosis/genetics , Cell Differentiation/genetics , Cell Proliferation/genetics , Epidermis/metabolism , Epidermis/pathology , Female , Flow Cytometry , Humans , Keratinocytes/metabolism , Male , Mesenchymal Stem Cells/metabolism , Middle Aged , Psoriasis/pathology , Skin/metabolism
13.
Poult Sci ; 90(4): 836-41, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21406370

ABSTRACT

Biliverdin is responsible for the coloration of blue eggs and is secreted onto the eggshell by the shell gland. Previous studies confirmed that a significant difference exists in biliverdin content between blue eggs and brown eggs, although the reasons are still unknown. Because the pigment is derived from oxidative degradation of heme catalyzed by heme oxygenase (HO), this study compared heme oxygenase (decycling) 1 (HMOX1), the gene encoding HO expression and HO activity, in the shell glands of the Dongxiang blue-shelled chicken (n = 12) and the Dongxiang brown-shelled chicken (n = 12). Results showed that HMOX1 was highly expressed at the mRNA (1.58-fold; P < 0.05) and protein levels in blue-shelled chickens compared with brown-shelled chickens. At the functional level, blue-shelled chickens also showed 1.40-fold (P < 0.05) higher HO activity than brown-shelled chickens. To explore the reasons for the differential expression of HMOX1, an association study of 6 SNP capturing the majority of HMOX1 variants with the blue egg coloration was performed. Results showed no significant association between SNP and the blue egg coloration in HMOX1 (P > 0.05). Taken together, these results show that blue egg formation is associated with high expression of HMOX1 in the shell gland of Dongxiang blue-shelled chickens, and suggest that differential expression of HMOX1 in the 2 groups of chickens is most likely to arise from an alteration in the trans-acting factor.


Subject(s)
Chickens/physiology , Egg Shell/physiology , Heme Oxygenase-1/metabolism , Pigmentation/physiology , Alleles , Animals , Biliverdine/metabolism , Blotting, Western/veterinary , Chi-Square Distribution , Chickens/genetics , Chickens/metabolism , Egg Shell/enzymology , Egg Shell/metabolism , Female , Genotype , Heme Oxygenase-1/biosynthesis , Heme Oxygenase-1/genetics , Pigmentation/genetics , Polymorphism, Single Nucleotide , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 14(6): 340-2, 324, 1994 Jun.
Article in Chinese | MEDLINE | ID: mdl-8000221

ABSTRACT

Huan-an Powder (HA) was used to prevent and treat the intrauterine device (IUD) caused abnormal menstruation in 155 cases, who were divided into the prevention group and treatment group. In the former, 70 cases had taken the powder, resulting in no obvious difference in their amounts of menstrual blood, menstrual period, menstrual cycle and hemoglobin between after and before the applying of IUD (P > 0.05). In the latter, there were 85 cases, of whom, 30 with hypermenorrhea, 30 with menostaxis, and 25 with preceded menstrual cycle, the total effective rate was 90%, 93% and 88% respectively. After HA was used, the amount of the menstrual blood was significantly reduced, the menstrual period markedly shortened (P < 0.01), while the menstrual cycle was prolonged and hemoglobin increased significantly (P < 0.01). The results showed that HA is a good recipe in preventing and treating abnormal menstruation caused by applying IUD, with highly effective and safe, and without any side effects and contraindications.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Intrauterine Devices/adverse effects , Menstruation Disturbances/drug therapy , Adult , Female , Hemoglobins/metabolism , Humans , Menorrhagia/drug therapy , Menorrhagia/etiology , Menstruation Disturbances/etiology , Menstruation Disturbances/prevention & control
17.
Neurotoxicol Teratol ; 9(5): 333-7, 1987.
Article in English | MEDLINE | ID: mdl-2826981

ABSTRACT

The radioprotective and neuromotor effects of WR-2721 were studied in male albino ICR strain mice. The protective activity was evaluated by graded doses of WR-2721 (50-400 mg/kg, IP) against whole body 60Co gamma irradiation at a single maximal lethal threshold dose rad (i.e., 1250 rad). The neuromotor effects of the drug were assayed by its action, at the same dose range as used in the protection assay, on spontaneous motor activity (SMA) and wire hanging performance (WHP). Drug doses were administered 30 min before radiation exposure and neurobehavioral testings. The results showed a dose-dependent increase in radioprotection and an inhibition in the neuromotor tasks. The radioprotective efficacy was seen at doses at which intrinsic neuromotor deficits were detected (100-400 mg/kg). A dose-related parallelism of protective efficacy and neurobehavioral toxicity (i.e., SMA inhibition and WHP disruption) was also observed. The present findings suggest that WR-2721 induces neuromotor dysfunctions along with its radioprotectivity.


Subject(s)
Amifostine/toxicity , Neuromuscular Junction/drug effects , Organothiophosphorus Compounds/toxicity , Amifostine/administration & dosage , Amifostine/pharmacology , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Radiation-Protective Agents
18.
Fundam Appl Toxicol ; 6(3): 506-14, 1986 Apr.
Article in English | MEDLINE | ID: mdl-3699334

ABSTRACT

The kinetics of the reactivation of acetylcholinesterase inhibited by isopropyl methylphosphonofluoridate was studied. The reactivators used include nine bispyridinium monooximes and three bispyridinium dioximes. The dissociation constant (Kd) and the rate constant (k2) of dephosphorylation of the complex formed from the organophosphorus acetylcholinesterase (OP-AChE) and the oxime were measured. The reactivation parameters obtained from the in vitro kinetic studies were used to elucidate the structure-activity relationships. The hydrophobic property of a nonoxime substituent at the 3-position on the pyridinium ring can exert a positive effect on their binding affinity to OP-AChE. However, the rate constants (k2) of the nucleophilic displacement of OP-AChE by oximes depend negatively on these physical and structural factors of the oximes. The correlations of the in vivo antidotal efficacy (ED50) of these bispyridinium oximes have been analyzed with their pharmacological properties, e.g., reactivation potency, antimuscarinic activities, and antinicotinic activities. However, no satisfactory correlations were observed. It may be concluded that the detoxication mechanism of poisoning by isopropyl methylphosphonofluoridate is different from those of pinacolyl methylphosphonofluoridate and paraoxon.


Subject(s)
Cholinesterase Reactivators/pharmacology , Organophosphorus Compounds/toxicity , Oximes/pharmacology , Acetylcholinesterase , Animals , Antidotes/pharmacology , Binding Sites , Cattle , Kinetics , Phosphorylation , Structure-Activity Relationship
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