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Objective:To determine the current status of multiple antibiotic residues in meat and meat products in Shanghai based on a 5-year surveillance， and perform the health risk assessment. Methods:We performed the examination in accordance with the Manual for National Food Contamination and Harmful Factor Risk Monitoring， and conduct health risk assessment according to the national limit standards on the monitoring data of 2016‒2020. Results:The total detection rate of multiple antibiotics in meat and meat products in Shanghai was determined to be 16.03%， in which the total unqualified rate was 1.97%. Moreover， the detection rate of quinolones was 2.78% and its unqualified rate was 0.83%. The unqualified rate of loxacin in cooked meat products was 2.12%. The detection rate of tetracyclines was 17.06% and its unqualified rate was 0.34%， in which the highest detection rate was identified in doxycycline （11.64%）. The detection rate of sulfonamides was 3.16%， in which the highest detection rate was in sulfamethazine （1.05%）. The detection rate of florfenicol was 5.15% and its unqualified rate was 0.12%. The difference of ofloxacin residues between diverse food categories （χ2=17.44， P<0.05） and processing links （χ2 =14.10， P<0.05） was statistically significant. In addition， the sum amount of ofloxacin， enrofloxacin and ciprofloxacin in cooked meat products was higher than other food categories； the unqualified rate and residual amount of ofloxacin available in online stores and catering links were both higher. The residual amount of doxycycline and the unqualified rate in the online store link were significantly higher than those in other links. Based on preliminary assessment， the high exposure values in the 97.5 percentile of meat and meat products accounted for a very low proportion of the corresponding acceptable daily intake （ADI） and posed a low health risk to the population. Conclusion:The total detection rate of tetracyclines in meat and meat products is relatively high， which obviously accumulates in the offals of livestock and poultry. In addition， some antibiotics， such as ofloxacin and doxycycline， are relatively high in catering and online stores. It is recommended to strengthen the supervision of quinolones in cooked meat products， especially ofloxacin， enrofloxacin， and ciprofloxacin， and improve the supervision of doxycycline in meat and meat products in online stores.
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Aim:To systematically design, synthesize and evaluate the biological activities of new threonine-based sulfonamide derivatives in order to achieve improved drug potency.Methodology: Sulfamoyl carboxylic acidswere prepared by the reaction of threonine with the appropriate sulfonyl chloride while their acetylated, carboxamide and aniline derivatives were synthesized via Lumiere-Barbier acetylation, Schotten-Baumann ammonolysis and Buchwald-Hartwig cross-coupling methods respectively. The FTIR, 1H-NMR, 13C-NMR and elemental analytical data were employed in the structural characterization. In vitro andin silico antioxidant and antimicrobial studies were carried out.Results:Compounds 1b and 1d displayed thebest in vitro antibacterial activities againstEscherichia coli, Salmonella typhi, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and antifungal activities against Candida albicansandAspergillus niger. Compound 1f (IC50= 1.150±0.003μg/ml) exhibited the best in vitro antioxidant activity. Compound 1a had a higherin silicoantibacterial (-11.51 kcal/mol) binding energies than antibacterial reference drug, penicillin (-10.89 kcal/mol). Compound 1c had the highest in silicoantifungal binding energy (-10.48kcal/mol)comparable to ketoconazole(-10.85 kcal/mol). Conclusion: All the compounds were found to be potential antioxidant and antimicrobial drug candidates having complied with Lipinski’s rule of five.
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SUMMARY Solubility of sulfadiazine (SD), sulfamerazine (SMR) and sulfamethazine (SMT) in cosolvent mixtures octanol+methanol was investigated to 278.15 K, 298.15 and 313.15 K. In all cases, the lowest solubility of each drug was obtained in pure octanol at 278.15 K. The maximum solubility depends on the polarity of the drug, thus SMR and SMT reached their maximum solubility in cosolvent mixtures methanol-rich. The solution thermodynamic functions were calculated from the experimental solubility data, using the van't Hoff and Gibbs equations, following the approach proposed by Krug et al. The enthalpy of solution is positive in all cases, which is an indication of the endothermic process with a marked entropic favor. Theoretical solubility and mean lethal concentration were calculated using the Abraham model.
RESUMEN Se investigó la solubilidad de sulfadiazina (SD), sulfamerazina (SMR) y sulfametazina (SMT) en mezclas codisolventes de octanol + metanol a 278,15 K, 298,15 y 313,15 K. En todos los casos, la solubilidad más baja de cada fármaco se obtuvo en octanol puro a 278,15 K. La solubilidad máxima depende de la polaridad del fármaco, por lo que SMR y SMT alcanzaron su máxima solubilidad en mezclas cosolventes ricas en metanol. Las funciones termodinámicas de solución se calcularon a partir de los datos experimentales de solubilidad, utilizando las ecuaciones de van't Hoff y Gibbs, siguiendo el enfoque propuesto por Krug et al. La entalpia de la solución es positiva en todos los casos, lo cual es una indicación del proceso endotérmico con un marcado favorecimiento entrópico. La solubilidad teórica y la concentración letal media se calcularon utilizando el modelo de Abraham.
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The purpose of this study is to find out whether there are broad cross-reactivity between antibacterial and nonantibacterial sulfonamide agents, the method of the study contained two parts, one is literature research mainlyfrom PubMed database by using the MeSH terms (“Drug name” + allergy); (“Drug name” + hypersensitivity);(“Drug name” + cross-allergenicity) and (“Drug name + cross-reactivity), the search drugs included somecommonly seen medication such as carbonic anhydrase inhibitor, COX-2 inhibitor, loop diuretic, sulfonylurea,thiazide and certain antiviral drugs; the other parts of this thesis is to conduct a statistical review, we screen outpatients who have a previous allergic history of antimicrobial sulfonamides from hospital medical record systemduring Jan 1st, 2015 to Dec 31th, 2016, we did a descriptive statistics of general patients medical information,analyze the suspect cases which patients present potential allergic reaction after using non-antimicrobialsulfonamides agents. Result of literature research reveal there are no convincing evidences and research toconfirm there are bored allergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamide inthe aspects of chemical structure, immunological study, and large scale population study as well; Result ofhospital patient’s statistics found out there are only 3 suspected cases that the patients were having adverseeffect during their pharmacotherapy from 506 cases. However, we did not found any strong correlation of broadallergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamides from these suspectedcases. Conclusion: There is minimal evidence of cross-reactivity between the antimicrobial sulfonamides and thenon-antimicrobial sulfonamides. However, the non-antimicrobial sulfonamides are rarely implicated inhypersensitivity reactions as well, so it is impossible to say with certainty that cross-reactivity does not occur.
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Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO2-NH2) and is one of the strongest pharmacological inhibitors of carbonic anhydrase activity. Acetazolamide is excreted unchanged in the urine. Here, we report on the development, validation and biomedical application of a stable-isotope dilution GC-MS method for the reliable quantitative determination of acetazolamide in human urine. The method is based on evaporation to dryness of 50 μL urine aliquots, base-catalyzed derivatization of acetazolamide (d0-AZM) and its internal standard [acetylo-2H3]acetazolamide (d3-AZM) in 30 vol％ pentafluorobenzyl (PFB) bromide in acetonitrile (60 min, 30 °C), reconstitution in toluene (200μL) and injection of 1-μL aliquots. The negative-ion chemical ionization (NICI) mass spectra (methane) of the PFB derivatives contained several intense ions including [M]- at m/z 581 for d0-AZM and m/z 584 for d3-AZM, suggesting derivatization of their sulfonamide groups to form N,N-dipenta-fluorobenzyl derivatives (R-SO2-N(PFB)2), i.e., d0-AZM-(PFB)2 and d3-AZM-(PFB)2, respectively. Quanti-fication was performed by selected-ion monitoring of m/z 581 and 83 for d0-AZM-(PFB)2 and m/z 584 and 86 for d3-AZM-(PFB)2. The limits of detection and quantitation of the method were determined to be 300 fmol (67 pg) and 1μM of acetazolamide, respectively. Intra-and inter-assay precision and accuracy for acetazolamide in human urine samples in pharmacologically relevant concentration ranges were determined to be 0.3％-4.2％and 95.3％-109％, respectively. The method was applied to measure urinary acetazolamide excretion after ingestion of a 250 mg acetazolamide-containing tablet (Acemit?) by a healthy volunteer. Among other tested sulfonamide drugs, methazolamide (MM, 236) was also found to form a N,N-dipentafluorobenzyl derivative, whereas dorzolamide (MM, 324) was hardly detectable. No GC-MS peaks were obtained from the PFB bromide derivatization of hydrochlorothiazide (MM, 298), xipamide (MM, 355), indapamide and metholazone (MM, 366 each) or brinzolamide (MM, 384). We demonstrate for the first time that sulfonamide drugs can be derivatized with PFB bromide and quan-titated by GC-MS. Sulfonamides with MM larger than 236 are likely to be derivatized by PFB bromide but to lack thermal stability.
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Sulfa drugs or sulfonamides were introduced in 1935 by the German physician Gerhard Domagk (1895-1964). Domagk worked closely with two chemists, Fritz Mietzsch and Josef Klarer. They worked together on compounds related to synthetic dyes, testing their effects on infectious diseases. Their concerted work eventually led to the discovery of Prontosil (sulfamidochrysoidine), the first sulfa drug that showed an incredible antibacterial effect on diseased laboratory mice. Soon after the introduction of sulfonamides, penicillin was discovered and hailed as a more effective and a safer alternative. The production of sulfonamides lost its enthusiasm with the introductions of even more antibiotics. However; anti-bacterial Sulfonamides are far from being obsolete despite the introduction of newer classes of antibiotics. Interest in their use has been revived in the 1980s with AIDS epidemic, when a combination of sulfamethoxazole and trimethoprim (SMX/TMP) was recognized as the drug of choice for the treatment of Pneumocystis jirovecii (PCP) pneumonia. This review article is intended to update clinicians with the many still current recommendations for sulfonamides both as therapeutic and prophylactic agents; with mechanism of action and resistance; and with adverse side effects that clinicians need to watch for while using this class of antimicrobial.
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Sulfonamides (SAs), such as sulfaguanidine (SGD), sulfadiazine (SDZ), sulfathiazole (STZ) and sulfamethazine (SMZ), can drastically inhibit the chemiluminescence (CL) intensities generated in both Ag-Luminol and Ni-Luminol systems.Based on these observations, a novel method of high performance liquid chromatography (HPLC) coupled with CL detection was established.Both the Ag-Luminol and Ni-Luminol CL systems were employed as detectors, and the performances of the two detecting systems were compared.After separated by HPLC, four SAs reacted with Ag-Luminol and Ni-Luminol CL system, respectively.Chromatographic conditions were as follows: reversed-phase C18 column (250 mm × 4.6 mm,5 μm), gradient elution, and 0.1% (V/V) formic acid-methanol as mobile phase with flow rate of 1 mL/min.CL conditions were as follows: [Ag]=1.4×10.-4 mol/L (in 0.12 mol/L NaOH);[Ni]=1.5×10.-5 mol/L (in 0.12 mol/L NaOH);[Luminol]=1.2×10.-7 mol/L;and flow rate=1.0 mL/min.Under the optimal conditions, the detection limits of Ag-Luminol CL system were 0.15, 0.96, 1.10, 1.50 μg/mL for SGD, SDZ, STZ, and SMZ, respectively, and the recovery were 81.0%-101.5%.Comparatively, the detection limits of Ni-Luminol CL system were 1.5, 17.2, 16.8 μg/mL for SGD, SDZ and STZ, and the recoveries was 83.9%-110.8%.The result showed that the Ag-Luminol CL system had a much better performance.The method was applied to the determination of the residues of the above four SAs in milk with satisfactory results.
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Extended Hildebrand Solubility Approach (EHSA) was applied to evaluate the solubility of sulfadiazine, sulfamerazine, and sulfamethazine in some ethanol + water mixtures at 298.15 K. Reported experimental equilibrium solubilities and some fusion properties of these drugs were used for the calculations. In particular, a good predictive character of EHSA (with mean deviations lower than 3.0%) were found by using regular polynomials in order four correlating the interaction parameter W with the Hildebrand solubility parameter of solvent mixtures without drug. The predictive character of EHSA was the same as that obtained by direct correlation of drug solubilities with the same descriptor of polarity of the cosolvent mixtures.
Se aplicó el Método Extendido de Solubilidad de Hildebrand (MESH) al estudio de la solubilidad de sulfadiazina, sulfamerazina y sulfametazina en mezclas binarias etanol + agua a 298,15 K. Se utilizaron valores reportados de solubilidad en equilibrio y algunas propiedades fisicoquímicas de fusión de estos compuestos. Se obtuvo una adecuada capacidad predictiva del MESH (con desviaciones promedio menores del 3,0%) al utilizar modelos polinómicos regulares de cuarto orden relacionando el parámetro de interacción W con el parámetro de solubilidad de Hildebrand de las mezclas solventes. El carácter predictivo del MESH fue de magnitud semejante al que se obtuvo calculando esta propiedad directamente, donde se utilizó una regresión empírica regular de cuarto orden de la solubilidad experimental logarítmica de los fármacos en función del parámetro de solubilidad de las mezclas disolventes.
Na presente investigação, aplicou-se o Método Estendido de Solubilidade do Hildebrand (MESH) ao estudo da solubilidade da sulfadiazina, sulfamerazina e sulfametazina em misturas binárias etanol + agua a 298,15 K. Obteve-se uma adequada capacidade preditiva (com menor desvio padrão de 3,0%) do MESH ao utilizar modelos polinomiais regulares de quarta ordem relacionando o parâmetro de interação W com o parâmetro de solubilidade do Hildebrand das misturas de solventes. O caráter preditivo do MESH foi semelhante ao obtido pelo cálculo utilizando uma regressão empírica regular da quarta ordem, da solubilidade experimental logarítmica dos fármacos em função do parâmetro de solubilidade das misturas dissolventes.
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A liquid chromatography_tandem mass spectrometric method was established for the determination of 25 kinds of veterinary antibiotics in manure, soil and water by ultrasonic_solid phase extraction. Purification efficiency of SAX cartridges for soil and manure samples extract and the procedure that manure samples defatted with hexane was also verified. The results showed that the average recoveries of the 25 target antibiotics were 50. 0%-121. 9%, the relative standard deviations (RSD) were 1. 1%-14. 71% (n=9), and the limits of detection (LOD) ranged from 0. 0002-0. 0560 μg/kg for soil and manure and ranged from 0. 002-0. 28 ng/L for water; After adding SAX cartridges, the matrix effects of manure samples reduced to 55%-120%, and soil samples to 75%-160%; after defatting by hexane extraction, the matrix effects of manure sample reduced to 55%-120%. This method has been employed to detect the veterinary antibiotics in environmental samples of livestock farm.
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Objective:To establish a determination method for sulfadoxine, sulfathiazole and sulfadiazine in animal derived prod-ucts by ultra-performance liquid chromatography-tandem mass spectrometry ( UPLC-MS/MS) . Methods:Trichloroacetic acid and ace-tonitrile were used in the extraction and removal of proteins. A Waters Acquity UPLC BEH C18 (100 mm × 2. 1 mm,1. 7 μm) column was used as the separation column. The mobile phase was 0. 1% formic acid in water-methanol with gradient elution. The three sulfona-mides residues were detected with multiple reaction monitoring( MRM) mode in multi-period. Results:Under the conditions,the linear range of sulfadoxine, sulfathiazole and sulfadiazine was 1. 0-200. 0 ng·ml-1 ,the linear correlation coefficient was above 0. 99,the re-covery was more than 70%,the detection limit was 0. 5 ng·ml-1 , and the quantification limit was 1. 0 ng·ml-1 . Conclusion: The sample preparation method is simple and fast, and the method can be used to analyze sulfadoxine, sulfathiazole and sulfadiazine in ani-mal derived food efficiently and sensitively.
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A method was developed for the determination of four sulfa antibiotics in groundwater, soil and excreta using solid phase micro extraction disks coupled with high performance liquid chromatography. The influence of eluent, different solid phase micro extraction membranes on the recovery of sulfa antibiotics in groundwater was investigated and it was found that when using the mixture of methyl alcohol and 1 . 0% formic acid as eluent, HLB ( divinyl benzene-N-vinyl pyrrolidone polymer ) as extraction membranes, an optimal enrichment effect was obtained. Different pretreatment methods for the 3 kinds of samples abovementioned were also examined. It was found that the signal response values obtained by using mixture of methyl alcohol and 1 . 0% formic acid as base solution of standard or sample solution was higher 8-10 times than that by using methyl alcohol only. Under the optimal conditions, good linear relationships were obtained in the sulfa antibiotics concentrations of 0 . 005-10 . 0 mg/L with the correlation coefficients>0 . 9999;The detection limits of sulfathiazole ( ST ) , sulfadiazine ( SM ) , sulfamethazine ( SM2 ) , sulfamethoxazole ( SMX ) were 1 . 08 , 3. 56, 4. 63 and 1. 84 ng/L(S/N=3), respectively. The enrichment factors for four sulfa antibiotics were 4000 times with solid phase micro extraction disks. The RSD of matrix spiked samples were 0. 1%-0. 4%(n=7). The proposed method was applied to the determination of the four sulfa antibiotics in groundwater, soil and excreta with spiked recoveries of the four sulfa antibiotics in the range of 69 . 80%-117 . 60%.
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To determine the residue of 14 sulfonamides in milk, a high performance liquid chromatography-tandem mass spectrometry ( HPLC-MS/MS ) method with on-line soild phase extraction ( SPE ) in cation exchange mode was established. 5 g of milk was extracted with 15 mL acetonitrile. Then the extraction was evaporated by 50 ℃ nitrogen and dissolved by 1. 00 mL 0. 2% formic acid. The dissolution was enriched and purified by MS/MS cation exchange on-line SPE column on a double ternary liquid chromatography, and eluted by the mixed solution of 2% ammonia methanol and 0. 2% formic acid (50:50, V/V). The compounds were separated by an octadecyl silica bonded column and determined by the tandem mass spectrometry. The results showed that the linearity of 14 sulfonamides was good in the range of 0 . 1–10 μg/kg ( r≥0 . 9995 ) . The LOD of the method was 0. 05 μg/kg, while the LOQ was 0. 1 μg/kg. The recoveries of the 14 sulfonamides were in the range of 60 %-90 %, while the inter-batch and intra-batch RSDs were all lower than 10%. The method was proved to be more convenient, economical and stable than the traditional SPE column method.
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Objective To investigate the effects,mechanisms,and the optimum doses of Rosuvastatin and Losartan on expression of caveolin-1 in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein(ox-LDL).Methods Human-monocyte cells were separated and changed into the human monocyte-macrophage cells.The model of amerosclerosis was set up.These cells were incubated in different doses of Rosuvastatin(0.1,1.0,5.0 μmol/L) and Losartan (10,50,100 μmol/L),and then cultured in combination of two drags (5.0 μmol/L + 100 μmol/L).Expression of caveolin-1 mRNA was determined with real-time fluorescent quantitative polymerase chain reaction (RT-PCR).Results In ox-LDL group,caveolin-1 mRNA was decreased sharply relative to control group [(0.2533 ±0.00973) vs (0.9410 ±0.03677)] in a concentration-dependent manner (P ＜0.01).Compared to ox-LDL group,expressions of Caveolin-1 mRNA were increased gradually in different doses of Rosuvastatin alone and Losartan alone group [(0.5198 ± 0.04840),(0.6183 ± 0.06740),(0.7257 ± 0.03052) vs (0.2533 ± 0.00973) ; (0.3350 ± 0.04177),(0.4428 ± 0.03804),(0.6049 ± 0.02627) vs (0.2533 ± 0.00973)] in a concentration-dependent manner (P ＜ 0.01) ; the summit expressions of caveolin-1 mRNA were emerged in using Rosuvastatin and Losartan together (F =59.119,P ＜ 0.01).Conclusions Rosuvastatin and Losartan may be responsible for the expression of caveolin-1 in human monocyte-macrophage cells that were induced by ox-LDL.The expressions were up-regulated with dose dependent manner of these drugs,and got the crest stage when using optimum doses of Rosuvastatin and Losartan together.
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A high-throughput method for screening drug multi residues was developed by quadrupole-time-of-flight( Q-TOF) mass spectrometry together with QuEChERS sample preparation technique. It has been used for the determination of 57 drugs, such as tetracyclines ( TCs ) , sulfonamides ( SAs ) , quinolones ( QNs ) , triphenylmethanes (TPMs), estrogens (ETs), androgens (AGs) and glucocorticoids (GCs) in fish. The optimized pretreatment conditions were examined. The target compounds were extracted with acetonitrile under the condition of Na2 EDTA-Mcllvaine buffer, and the usage of clean-up reagents was 25 mg anhydrous magnesium sulfate, 12. 5 mg octadecylsilane and 6. 25 mg N-Propylethylenediamine sorbent for extracted solvent of each milliliter. The positive results acquired by this high-throughput method were confirmed by liquid chromatography-tandem mass spectrometry ( LC-MS/MS) . The detection limit for these 59 drugs was in the range of 0. 5-5. 3 μg/kg. The method is time-saving, convenient, effective and wide coverage. Its sensitivity can meet the requirement of the detection of drug residues in aquatic products.
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En este trabajo se propone y se valida una metodología analítica por espectrofotometría UV aplicada al estudio de la solubilidad de algunas sulfonamidas en mezclas cosolventes. Los parámetros evaluados fueron: especificidad, linealidad, precisión y límites de detección y cuantificación, así como la estabilidad de los fármacos bajos las condiciones de análisis de solubilidad. El método propuesto es útil para determinar la solubilidad de estas sulfonamidas en función de la temperatura y la composición cosolvente.
An analytical method by UV-spectrophotometry has been proposed and validated to study the solubility of some sulfonamides in cosolvent mixtures. The parameters evaluated were specificity, linearity, precision, and detection and quantification limits, as well as the drug stability under the solubility analysis conditions. The developed method was useful to determine the solubility of these drugs as a function of temperature and cosolvent concentration.
Neste trabalho propomos é validamos uma metodologia analítica ultravioleta para o estudo da solubilidade de alguns sulfamidas em misturas dos solventes. Os parâmetros avaliados foram: especificidade, linearidade, precisão, exatidão e limites de detecção e quantificação, e a estabilidade dos fármacos nas condições de estúdio. O método proposto é útil para a determinação da solubilidade destes sulfamidas em função da temperatura e da composição do cosolvente.
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En este trabajo se propone y se valida una metodología analítica por espectrofotometría UV aplicada al estudio de la solubilidad de algunas sulfonamidas en mezclas cosolventes. Los parámetros evaluados fueron: especificidad, linealidad, precisión y límites de detección y cuantificación, así como la estabilidad de los fármacos bajos las condiciones de análisis de solubilidad. El método propuesto es útil para determinar la solubilidad de estas sulfonamidas en función de la temperatura y la composición cosolvente.
An analytical method by UV-spectrophotometry has been proposed and validated to study the solubility of some sulfonamides in cosolvent mixtures. The parameters evaluated were specificity, linearity, precision, and detection and quantification limits, as well as the drug stability under the solubility analysis conditions. The developed method was useful to determine the solubility of these drugs as a function of temperature and cosolvent concentration.
Neste trabalho propomos é validamos uma metodologia analítica ultravioleta para o estudo da solubilidade de alguns sulfamidas em misturas dos solventes. Os parâmetros avaliados foram: especificidade, linearidade, precisão, exatidão e limites de detecção e quantificação, e a estabilidade dos fármacos nas condições de estúdio. O método proposto é útil para a determinação da solubilidade destes sulfamidas em função da temperatura e da composição do cosolvente.
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Objective To investigate the effects and mechanism of different doses of rosuvastatin on expression of tissue factor(TF) in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein (ox-LDL).Methods The human monocyte-macrophage cells were divided into seven groups:control group,ox-LDL group,poly-insine monophosphate group,different doses of rosuvastatin group(0.01 μmol/L,0.1 μmol/L,1 μmol/L,5 μmol/L).The expression of LOX-1 mRNA and TF mRNA was assayed by RT-PCR.The enzyme-linked immunosorbent assay was performed to determine the protein concentration of TF.Results Effects of different doses of rosuvastatin on expressions of LOX-1mRNA,TF mRNA and TF in cultured human monocyte-macrophage cells induced by ox-LDL:comparison among seven groups,the difference was statistically significant (F =91.334,58.833,103.552,P ＜0.05).Compared with control group,the expressions of LOX-1 mRNA,TF mRNA and TF were increased in the ox-LDL group[(3.25156 ± 0.15772) vs (1 ±0) ;(2.522451 ±0.138967) vs (1 ±0) ;(207.7233± 1.154701)ng/L vs (184.8467 ± 0.871799)ng/L],and they were in a concentration-dependent manner (P ＜ 0.05).Compared with the PolyⅠ group and the different doses of rosuvastatin group,the expressions of LOX-1 mRNA,TF mRNA and TF were in the ox-LDL group,and the different doses of rosuvastatin were decreased by dose-dependent manner.It was in a concentration dependent manner (P ＜ 0.05).Different doses of rosuvastatin were compared between groups (between each group P ＜ 0.05),the difference between each two groups was statistically significant (P ＜ 0.05).Conclusions LOX-1 may be responsible for the expression of TF in Human monocyte-macrophage cells induced by ox-LDL.Rosuvastatin by dose dependent manner and by means of ox-LDL reduced monocyte-macrophage LOX-1 mRNA and TF mRNA expressions,which reduced expression of TF.
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This manuscript reports the synthesis of a series of N-substituted derivatives of 2-phenitidine. First, the reaction of 2-phenitidine (1) with benzene sulfonyl chloride (2) yielded N-(2-ethoxyphenyl) benzenesulfonamide (3), which further on treatment with sodium hydride and alkyl halides (4a-g) furnished into new sulfonamides (5a-g). Second, the phenitidine reacted with benzoyl chloride (6) and acetyl chloride (8) to yield the reported N-benzoyl phenitidine (7) and N-acetyl phenitidine (9), respectively. These derivatives were characterized by infrared spectroscopy, ¹H-NMR, and EI-MS, and then screened against acetylcholinesterase, butylcholinesterase, and lipoxygenase enzyme, and were found to be potent inhibitors of butyrylcholinesterase alone.
Este trabalho apresenta a síntese de uma série de derivados da 2-fenetidina N-substituídos. Primeiro, a reação da 2-fenetidina (1) com cloreto de benzenossulfonila (2) conduziu à N-(2-etoxifenil)benzenossulfonamida (3) que, após tratamento com hidreto de sódio e haletos de alquila (4a-g), originou novas sulfonamidas (5a-g). Em segundo lugar, a reação da fenetidina com cloreto de benzoíla (6) e cloreto de acetila (8) conduziu, respectivamente, à N-benzoilfenetidina (7) e N-acetilfenetidina (9). A caracterização destes derivados fez-se por IV, ¹H-RMN e EM-IE. Procedeu-se à avaliação da atividade inibidora destes compostos em relação às enzimas acetilcolinesterase, butirilcolinesterase e lipoxigenase. No entanto, apenas revelaram atividade inibidora da butirilcolinesterase.
Subject(s)
Phenetidine/analysis , Sulfonamides/analysis , Butyrylcholinesterase/analysis , Acetamides/analysisABSTRACT
Se realizó un estudio descriptivo y transversal de 47 médicos (15 especialistas en Medicina General Integral, 2 en Medicina Interna, 1 en Geriatría y 30 internos) que recetaron antimicrobianos a ancianos con infecciones del tracto urinario en el área de salud del Policlínico Docente "Carlos Juan Finlay" de Santiago de Cuba, desde enero hasta junio del 2010, a fin de evaluar dichas prescripciones. Los resultados de la serie mostraron adecuadas disponibilidad de los medicamentos y accesibilidad a ellos, así como suficiente cantidad de prescriptores para brindar el servicio, aunque el mayor número de estos tuvo insuficientes conocimientos sobre el tema, lo que fue más evidente en los internos y médicos generales integrales. Predominaron las infecciones del tracto urinario alta y baja y la bacteriuria asintomática, así como las indicaciones de los fármacos: quinolonas, sulfonamidas y betalactámicos. La mayoría de las prescripciones fueron inadecuadas, fundamentalmente por dificultades en la individualización del tratamiento, y un elevado porcentaje de pacientes presentó reacciones adversas medicamentosas, con predominio de las manifestaciones leves.
A descriptive cross-sectional study was carried out in 47 physicians (15 specialists in Comprehensive General Medicine, 2 in Internal Medicine, 1 in Geriatrics and 30 interns), who prescribed antibiotics for the elderly with urinary tract infections in the health area of "Carlos Juan Finlay" Teaching Polyclinic of Santiago de Cuba, from January to June 2010, in order to evaluate these prescriptions. The results of the series showed adequate availability of drugs and access to them, as well as prescriptors enough to offer this service, although most of them had insufficient knowledge of the subject, being more evident in interns and general practitioners. Infections of the upper and lower urinary tract and asymptomatic bacteriuria prevailed, as well as indications of drugs such as quinolones, sulfonamides and beta-lactams. Most prescriptions were inappropriate, mainly because of difficulties in the individualization of treatment, and a high percentage of patients experienced adverse drug reactions, predominantly mild manifestations.
ABSTRACT
An efficient method is provided to detect simultaneously some important veterinary drugs from different classes in highly complex animal tissue matrix.This method using matrix solid-phase dispersion (MSPD) and high performance liquid chromatography (HPLC) with diode array detection (DAD) is developed to effectively determine two fluoroquinolones (enoxacin and lomefloxacin),two sulfonamides (sulfanilamide and sulfamethoxazole) and one tetracycline (tetracycline) simultaneously in porcine tissues.In the process,MSPD methodology was used to treat samples,washed by n-hexane to remove lipid,eluted the analytes with acetonitrile-dichloromethane (1∶1,v/v).Solvent acetonitrile and solvent acetic acid (0.1％) were combined in a gradient.HPLC-DAD analysis of the tissue samples was performed within 15min at a flow rate of 1.0mL/min.The results showed that a recovery at 0.1,0.5 and 1.0 μg/g fortification levels ranged from 80.6％ to 99.2％ with satisfactory relative standard deviations (RSDs) (below 6.1％.n=3) and the limits of quantitation (LOQ) ranged from 7 μg/kg to 34 μg/kg in porcine tissues.Utilization of the method in successfully simultaneous analysis of porcine tissue incurred with veterinary drug multiresidues is described.