The paper is aimed to establish a method of residue analysis for thiamethoxam and to study its degradation dynamic and final residue and its standard of safe application of thiamethoxam on Lonicera japonica. Samples extracted with methanol by ultrasonication were purified with dichloromethane by liquid-liquid extraction and SPE column and analysed by HPLC-UV. The results showed that average rate was 84.91%-94.44% and RSD 1.74%-4.96% with addition of thiamethoxam in respectively diverse concentration, which meets inspection requirement of pesticide residue. Two kinds of dosages of thiamethoxam were treated- varying from recommended dosage (90 g x hm(-2)) to high dosage (135 g x hm(-2)), Results of two years test showed that thiamethoxam was degraded more than 90% seven days after application and the half - life period of thiamethoxam was 1.54-1.66 d. The digestion rate of thiamethoxam was fast in the L. japonica. The recommended MRL of thiamethoxam in the L. japonica is 0.1 mg x kg(-1), the dosage of 25% thiamethoxam WDG from 90-135 g x hm(-2) is sprayed less than three times a year on L. japonica and 14 days is proposed for the safety interval of the last pesticide application's and harvest's date.
Agriculture ; methods ; standards ; Chromatography, High Pressure Liquid ; Flowers ; chemistry ; growth & development ; parasitology ; Half-Life ; Insect Control ; methods ; standards ; Insecticides ; adverse effects ; chemistry ; Lonicera ; chemistry ; growth & development ; parasitology ; Neonicotinoids ; Nitro Compounds ; adverse effects ; chemistry ; Oxazines ; adverse effects ; chemistry ; Pesticide Residues ; adverse effects ; chemistry ; Plant Diseases ; parasitology ; prevention & control ; Thiazoles ; adverse effects ; chemistry

Objective: To evaluate and compare the effects of bevacizumab, mitoinycin-C (MMC), 5-fluorouracil (5-FU), and triamcinolone acetonide (TA) on the viability of cultured human Tenon's capsule fibroblasts (cHTF) in vitro.

Methods: Human Tenon's fibroblasts (HTF) were harvested and cultured in a Roswell-Park-Memorial 1-Institute (RPMI) media. MMC, 5-FU, bevaciz. umab, and TA were administered to the cHTF at 3-fold decreasing concentrations starting from 20 ug, 5 mg, 25 mg, and 4 mg respectively. A negative control/untreated group containing RPMI media only was included in the study. Fibroblast cell viability was assessed using resazurin fluorim etric assay. Half¬maximal inhibitory concentration (IC50) was computed for agents which showed significant decrease in cHTF viability compared to the untreated group.

Results: There was no significant difference in cH IF viability between the untreated control group compared to 5-FU (p=0.97), bevacizumab (p=0.10), and TA (p=0.06) groups. Mitomycin-C showed a significant decrease in cHTF viability (p<0.001) which was dose dependent. The IC50 of MMC was computed at 12.16 ug using the prism software.

Conclusion: Mitomycin-C demonstrated dose-dependent decrease in viability of cultured human Tenon's fibroblasts. 5-FU, bevacizumab, and triamcinolone did not show this effect.

Key Words: Mitomycin-C, 5-fluorouracil, Bevaciz. umab, Tria. mcinolone acetonide, Fibroblast, Trabeculectomy

Human ; Male ; Female ; .humans ; Mitomycin ; Triamcinolone Acetonide ; Trabeculectomy ; Resazurin ; Bevacizumab ; Fluorouracil ; Cell Survival ; Control Groups ; Inhibitory Concentration 50 ; Tenon Capsule ; Xanthenes ; Oxazines ; Antibodies, Monoclonal, Humanized ; Fibroblasts ; Software

PURPOSE: Indoxacarb insecticide poisoning causes methemoglobinemia, which is occasionally life-threatening. However, there is limited data on indoxacarb effects after human ingestion. The purpose of this study was to examine the clinical features, complications, management, and medical outcome of patients with indoxacarb insecticide poisoning. METHODS: We retrospectively reviewed the medical records of 10 patients with indoxacarb insecticide poisoning who had visited our emergency centers from January 2008 to December 2011. We collected data on the general characteristics of the patients, their clinical symptoms and signs, laboratory data, management of their condition, and clinical results. RESULTS: Among the 10 patients, 8 were diagnosed with methemoglobinemia. The clinical manifestations of indoxacarb insecticide poisoning were hypotension (3 patients), altered mentality (5 patients), cyanosis (5 patients), dyspnea (2 patients), seizure (3 patients), and cardiac arrest (2 patients). Four patients had a poisoning severity score of 3 and 2 patients had a poisoning severity score of 2. Four patients were treated with methylene blue for methemoglobinemia and one patient was treated with a high dose (150 mg/kg) of ascorbic acid. The serum methemoglobin saturation of five patients who were treated with methylene blue or a high dose of ascorbic acid was nearly normalized. Four patients experienced rhabdomyolysis, pneumonia, hemolytic anemia, acute pancreatitis, and heart failure as a complication of indoxacarb insecticide poisoning. CONCLUSION: We observed a variety of clinical features, complications, management, medical outcome, and clinical course of patients with indoxacarb insecticide poisoning. We could also ascertain the efficacy of methylene blue and high dose ascorbic acid for indoxacarb-induced metheglobinemia.
Anemia, Hemolytic ; Ascorbic Acid ; Cyanosis ; Dyspnea ; Eating ; Emergencies ; Heart Arrest ; Heart Failure ; Humans ; Hypotension ; Medical Records ; Methemoglobin ; Methemoglobinemia ; Methylene Blue ; Oxazines ; Pancreatitis ; Pneumonia ; Retrospective Studies ; Rhabdomyolysis ; Seizures

OBJECTIVETo establish a rapid and sensitive high-performance liquid chromatography (HPLC) method for detecting pazufloxacin concentrations in the saliva, gingival crevicular fluid and serum of healthy adults.

METHODSSamples of saliva, gingival crevicular fluid and serum were obtained from healthy adults receiving intravenous infusion of pazufloxacin. The concentrations of pazufloxacin in the samples were quantified by HPLC equipped with a reversed-phase column (Agilent Zorbax SB-C18 5 µm, 250 mm×4.6 mm). The mobile phase for pazufloxacin was a mixture of acetonitrile and 0.5% phosphoric acid containing 1% triethylamine (155:850), and 20 µl of the resulting solution was injected into the HPLC system at a flow rate of 1.0 ml/min. The detection wavelength was set at 245 nm. The samples were first deproteinized by precipitation with methanol followed by supernatant drying; the residue was reconstituted with the mobile phase and centrifuged, and the supernatants were directly injected into the HPLC system.

RESULTSPazufloxacin in the samples were totally separated without interference by any endogenous substances. The calibration curves showed a good linear regression (r>0.999). The detection limit was 10 ng/ml with within-day and between-day coefficients of variation performance all below 5% and recovery rates all above 91%.

CONCLUSIONHPLC is both sensitive and selective for quantification of pazufloxacin in saliva, gingival crevicular fluid and serum.

Adult ; Chromatography, High Pressure Liquid ; methods ; Female ; Fluoroquinolones ; analysis ; blood ; Gingival Crevicular Fluid ; chemistry ; Humans ; Male ; Oxazines ; analysis ; blood ; Saliva ; chemistry ; Sensitivity and Specificity ; Young Adult

PURPOSE: To investigate the effects of dipyridamole (DPD) on the production of reactive oxygen species (ROS) and oxidative stress in cultured human trabecular meshwork cells (HTMC). METHODS: Antioxidant activity of DPD was determined by DPPH assay. Primarily cultured HTMC were exposed to 0, 20, and 50 microm DPD using serum-deprived media. The effect of DPD on the production of ROS was assessed with the DCHFDA assay. The effect of DPD on the t-butyl hydroperoxide (tBHP)-induced oxidative stress was assessed with resazurin assay. RESULTS: DPD showed significant antioxidant activity. DPD significantly decreased the production of ROS (p < 0.05) and improved cellular activity significantly after treatment with t-BHP (p < 0.05). DPD did not affect the generation of nitric oxides. CONCLUSIONS: DPD suppressed the formation of ROS and possessed cytoprotective activity against the oxidative stress in HTMC.
Dipyridamole ; Humans ; Oxazines ; Oxidative Stress ; Reactive Oxygen Species ; tert-Butylhydroperoxide ; Trabecular Meshwork ; Xanthenes

LIVE/DEAD(R) BacLight(TM) and alamarBlue(R) are fluorescent materials used for the enumeration of live and dead bacteria. LIVE/DEAD(R) BacLight(TM) is generally used for confocal microscopy applications to differentiate live from dead bacteria in a biofilm or planktonic state. AlamarBlue(R) has also been used widely to assay live and dead bacteria in a planktonic state. Whilst these materials are successfully utilized in experiments to discriminate live from dead bacteria for several species of bacteria, the application of these techniques to oral bacteria is limited to the use of LIVE/DEAD(R) BacLight(TM) in biofilm studies. In our present study, we assessed whether these two methods could enumerate live and dead oral bacterial species in a planktonic state. We tested the reagents on Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Enterococcus faecalis and found that only LIVE/DEAD(R) BacLight(TM) could differentiate live from dead cells for all five of these oral strains. AlamarBlue(R) was not effective in this regard for P. gingivalis or A. actinomycetemcomitans. In addition, the differentiation of live and dead bacterial cells by alamarBlue(R) could not be performed for concentrations lower than 2 x 10(6) cells/ml. Our data thus indicate that LIVE/DEAD(R) BacLight(TM) is a more effective reagent for this analysis.
Bacteria ; Biofilms ; Enterococcus faecalis ; Fluorescence ; Indicators and Reagents ; Microbial Viability ; Microscopy, Confocal ; Oxazines ; Plankton ; Porphyromonas gingivalis ; Streptococcus mutans ; Streptococcus sobrinus ; Viridans Streptococci ; Xanthenes

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting diarthroidal joints. Following the successful application of biologic agents, several small molecule inhibitors are currently under clinical trials. Small molecule inhibitors have several strengths compared with biologics. First, they can target several inflammatory cytokines together by blocking common signal transduction pathways. Second, they can be taken orally. Third, the price can be made flexible. Among the several small molecule inhibitors in the development process, fostamatinib and tofacitinib are the closest to the clinics at the moment. Fostamatinib, which is a Syk inhibitor, showed superior efficacy over placebo with tolerable safety signals. Diarrhea, hypertension and infection are representative adverse events. Tofacitinib, which is JAK inhibitor, is now finishing phase 3 clinical trials. It showed clinical efficacy comparable to Adalimumab and similar adverse effect profiles to the biologics, which include opportunistic infections. For laboratory abnormalities, leukopenia, anemia, increase of LDL and serum Cr were reported, which, however, were stabilized with prolonged use. Other classes of small molecule inhibitors did not show impressive efficacy as these small molecule inhibitors. In conclusion, small molecule inhibitors are promising novel therapeutic agents for the treatment of RA. They will be able to change the treatment paradigm of RA if they can show long-term safety.
Anemia ; Antibodies, Monoclonal, Humanized ; Arthritis, Rheumatoid ; Biological Agents ; Cytokines ; Diarrhea ; Hypertension ; Joints ; Leukopenia ; Opportunistic Infections ; Oxazines ; Piperidines ; Pyridines ; Pyrimidines ; Pyrroles ; Signal Transduction

Indoxacarb is an oxadiazine insecticide with selective lethality through blockade of neuronal voltage-dependent sodium channels. It has a low mammalian toxicity, and few cases of human toxicity after indoxacarb ingestion can be found in the literature. A 36 year-old male patient visited our ED after a generalized tonic clonic seizure, which was witnessed by his mother. His past medical history was nonspecific. On initial presentation, he showed a decreased level of consciousness with a Glasgow coma score of 5/15 (E1V1M3), unprotected airway, hypoxia, and cyanosis. The saturation gap and cyanosis after intubation and mechanical ventilation was strongly suggestive of methemoglobinemia due to poisoning. Finally, the methemogobin (metHb) level was 27.4%. Therefore, the patient received 100 mg of methylene blue (2 mg/kg, 1% solution) and 50 g of charcoal. The insecticide was found to be ingested xenobiotic (Steward Gold(R); 5% indoxacarb; 95% inert ingredients and other components). On the second hospital day, the patient became alert. The patient's metHb level was 0.1%. The endotracheal tube was removed. On the fifth hospital day, he was discharged in good condition. Herein we present a case of indoxacarb poisoning with methemoglobiemia and seizure, which are unusual presentations.
Anoxia ; Charcoal ; Coma ; Consciousness ; Cyanosis ; Eating ; Humans ; Intubation ; Male ; Methemoglobinemia ; Methylene Blue ; Mothers ; Neurons ; Oxazines ; Respiration, Artificial ; Seizures ; Sodium Channels ; Wit and Humor as Topic

Compounds with serotonin reuptake inhibition/5-HT(1A) dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio. Based on the model, 8 novel aryl piperazine benzo[b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI(1) and VI(7) showed potent functional activities at both 5-HT transporter and 5-HT(1A) receptor, which can be used as lead compounds to guide future research of design and synthesis of potent novel compounds.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Drug Design ; Genetic Vectors ; Molecular Structure ; Oxazines ; chemical synthesis ; chemistry ; pharmacology ; Piperazines ; chemical synthesis ; chemistry ; pharmacology ; Plasmids ; Protein Binding ; Receptor, Serotonin, 5-HT1A ; genetics ; metabolism ; Serotonin Plasma Membrane Transport Proteins ; genetics ; metabolism ; Serotonin Uptake Inhibitors ; metabolism ; Structure-Activity Relationship ; Transfection

BACKGROUND: Propofol directly inhibits vascular reactivity. However, available information regarding the underlying mechanisms of propofol is poor. Therefore, mechanisms of the underlying relaxant action of propofol were investigated using rabbit renal arteries. METHODS: Propofol-induced relaxation of rabbit renal arteries was studied in contracted preparations with 50 mM KCl or 10microM histamine. Vessel tension was recorded with a pen recorder. We were interested in determining whether propofol-induced vasodilation is affected by endothelium-denudation, L-NG-nitroarginine methyl ester (L-NAME), tetraethylammonium (TEA), iberiotoxin, glibenclamide, 4-aminopyridine, 7-ethoxyresorufin, caffeic acid, baiclalein, ryanodine, and thapsigargin. RESULTS: Propofol-induced concentration-dependent vasodilation was not affected either by endothelium denudation or by L-NAME during histamine-induced contraction. The relaxing effect of propofol on histamine-induced contraction was inhibited by either TEA, a K+ channel inhibitor, or iberiotoxin (100 nM), a selective blocker of the large conductance Ca(2+)-activated K+ channel (BKCa channel). In contrast, the relaxing effect of propofol was unaffected by 10microM glibenclamide, an ATP-sensitive K+ channel blocker, by 5 mM 4-aminopyridine, a blocker of delayed rectifier, by 7-ethoxyresorufin, a cytochrome P450 inhibitor, by 10microM caffeic acid and 10microM baiclalein, lipooxygenase inhibitors, or by 10microM ryanodine and thapsigargin, Ca2+store inhibitors. CONCLUSIONS: These results suggest that the relaxant effect of propofol may result from activation of BKCa channels by inhibiting voltage-gated Ca2+ influx in a prolonged manner.
4-Aminopyridine ; Caffeic Acids ; Contracts ; Cytochrome P-450 Enzyme System ; Endothelium ; Glyburide ; Glycosaminoglycans ; Histamine ; NG-Nitroarginine Methyl Ester ; Oxazines ; Peptides ; Propofol ; Relaxation ; Renal Artery ; Ryanodine ; Tea ; Tetraethylammonium ; Thapsigargin ; Vasodilation