Discovery of novel sulfonamide substituted indolylarylsulfones as potent HIV-1 inhibitors with better safety profiles

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R10L4 was endowed with significant inhibitory activity towards wild-type HIV-1 (EC50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC50 = 0.017 μmol/L, SI = 13,055), E138K (EC50 = 0.017 μmol/L, SI = 13,123) and Y181C (EC50 = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R10L4 was characterized with significantly reduced cytotoxicity (CC50 = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R10L4 and HIV-1 RT. Additionally, R10L4 presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups / 药学学报

Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole. TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.

Advances in biodegradation of sulfonamides antibiotics in aerobic activated sludge system / 生物工程学报

Sulfonamides (SAs) are a kind of antibiotics widely used in medical treatment and livestock breeding. However, they have poor degradability in human and animal intestines, and will enter the sewage treatment system through the discharge of feces and urine. The aerobic activated sludge (AAS) in wastewater treatment plant was found to be able to effectively transform SAs. This article summarizes the advances in biodegradation of SAs in aerobic activated sludge system, which includes the biodegradation mechanisms, the main biodegradation pathways, and the environmental factors affecting the degradation efficiency. Challenges encountered in the current research were discussed, with the aim to provide scientific basis for optimizing the biodegradation of SAs in wastewater treatment process.

Adsorption Properties of Thermally Treated Rice Husk for Removal of Sulfamethazine Antibiotic from Pharmaceutical Wastewater

Equilibrium sorption of the Thermally Treated Rice Husk (TTRH) for Sulfamethazine (SMT) adsorption was studied. The Physico-chemical properties of the modified rice husk were determined. The equilibrium sorption data were fitted into Langmuir, Freundlich and Dubinin–Radushkevich isotherms. Of the three adsorption isotherm, the R2value of Langmuir isotherm model was the highest. Also compared to other isotherms the AARE coefficient for the Langmuir isotherm is low,which indicates favorable sorption. The maximum monolayer coverage (qm) from Langmuir isotherm model was determined to be 19.11 mg/g, the separation factor indicating a favorable sorption experiment is 0.446. Also from Freundlich Isotherm model, the sorption intensity (n) which indicates favorable sorption andthe correlation value are 1.84 and 3.79 respectively. The mean free energy was estimated from Dubinin–Radushkevich isotherm model to be 9.18 KJ/mol which clearly proved that the adsorption experiment followed a physical process

Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Physicochemical Equivalence and Validation of an HPLC Analytical Method for the Quantification of Glibenclamide and Its Sulfonamide Impurity in Prescribed Glibenclamide Tablets in Nigeria

Objective: To investigate the physicochemical equivalence of four brands of commercially available glibenclamidetablets in Nigeria and to develop a validation method using HPLC for the quantitative determination of glibenclamide and its sulfonamide impurity present in thesetablets.Methods: Uniformity of weight, friability tests, hardness/crushing strength, dissolution,anddisintegration tests were carried out on tablets/drug samples of each brand. Theirfunctional groups were determined and compared with pure glibenclamide sample (reference standard) using Fourier Original Research Article Transform Infrared Spectroscopy (FTIR) between a range of 4000cm-1to 400cm-1. High-Performance Liquid Chromatography (HPLC) was used to determine the percentage of glibenclamide and its sulfonamide impurity present in each tablet brand. Results: From the physicochemical evaluation of the four brands ofglibenclamide tablets tested, the brands passed all the British Pharmacopeia specifications,but they all failed the hardness/crushing strength tests and one of the brands failed the assay test requirement for drug content. The developed HPLC method had apercentage recovery between the acceptable limit of 95-105% with percentage relative standard deviation (%RSD) of < 3% while the precision of the method was 0.102%and 0.383% for glibenclamide and its sulfonamide impurity, respectively. The Limit of Detection (LOD)and Limit of Quantification (LOQ)of the developed analytical method for the four brands were 0.075μg/ml and 0.227μg/ml for glibenclamide while that of sulfonamide impurity were0.114μg/ml and 0.345μg/ml,respectively.In addition, the percentage impurity of sulfonamide in all the brands was less than the acceptable limit of 1%.Conclusion: Theresultsfrom thephysicochemical evaluation of the glibenclamide brands justified the need forconstant monitoring of marketed drug products. The results obtained from theHPLC quantification methoddeveloped for this study show that our data is reproducible based on the linearity, precision, and accuracyof data generated forglibenclamide and its sulfonamide impurity inthe four brands of glibenclamide tablets prescribed to DM patients in Nigeria, which were judged to besatisfactoryat the time of this study

Statistical Analysis of Sulfonamide Allergy Item Annotation in Drug Instructions of Commonly-used Sulfonylureas at Home and Abroad / 中国药房

OBJECTIVE： To investigate sulfonamide allergy item annotation in drug instructions of sulfonylureas， and to provide reference for the promoting rational clinical use of the drugs. METHODS： In Oct. 2018， the drug instructions of commonly-used sulfonylureas at home and abroad were collected by MCDEX software （online version）， Drugs@FDA of the US Food and Drug Administration website， DailyMed website， European Medicines Agency website and UK electronic Medicines Compendium website. The annotation of sulfonamide allergy was analyzed statistically in respects of non-labeled sulfonamide allergy， only labeled sulfonamide allergy contraindication， only labeled sulfonylureas allergy contraindication， labeled sulfonamide and sulfonylureas allergy contraindication. The proportion of sulfonamide allergy contraindication labelling was calculated. RESULTS： Among 174 pieces of domestic drug instructions， 67 pieces of drug instructions were gliclazide， 48 were glipizide， 23 were glibenclamide， 23 were glimepiride and 13 were gliquidone. Different pharmaceutical manufacturers reached a consensus on the sulfonamide allergy of gliquidone and glibenclamide. The proportions of sulfonamide allergy contraindication labelling were 100％ and 95.65％， respectively. However， there were great differences on the sulfonamide allergy of glipizide， glimepiride and gliclazide， and the proportions of sulfonamide allergy contraindication labelling were 70.83％， 65.22％ and 49.25％， respectively. Among 13 foreign drug instructions， 4 pieces of drug instructions were glibenclamide， 3 were glipizide， 3 were glimepiride， and 3 were gliclazide， among which 7 drug instructions were sulfonamide allergy contraindication. However， there were great differences in the sulfonamide allergy annotation of drug instructions between US and Europe. CONCLUSIONS： There are great differences in the annotation for sulfonamide allergy in drug instructions of sulfonylureas at home and abroad， which indicates that there are different opinions on the clinical significance of sulfa cross-reaction in patients with sulfonamide allergy， and sulfonamide cross-allergy is a controversial issue. It is necessary to promote the research of sulfonamide cross-allergy from the perspectives of scientific researchers， medical associations， pharmaceutical manufacturers， medical staff and patients，  and to clarify its mechanism and clinical significances.

Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis of 16 Kinds of Residual Antibiotics in Chicken Manure / 分析化学

A sensitive and effective method for determination of 16 kinds of antibiotics, including tetracycline, sulfonamide, fluoroquinolone and macrolide, in livestock and poultry manure using solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.Aiming at the chemical properties and sample impurities of the target, the parameters such as mass spectrum conditions, types of extraction and ultrasonic power were optimized.Finally, the samples were extracted with 50% acetonitrile in phosphate buffer solution (pH =4) for three times, followed by ultrasonic steaming, centrifugal and rotary, dilution, and purified by SAX-HLB.After sample loading, the solid phase was washed with 10 mL of methanol-acetone (80∶20, V/V), evaporated to near dryness at 35℃, and then re-dissolved and vortex mixed in 1 mL of 0.1% formic acid∶methanol (1∶1, V/V).The extracts were analyzed with UPLC-MS/MS and calculated by external standard method based on the monitored product ion.The results indicated that the average spiked recoveries of tetracycline, sulfonamide, fluoroquinolone and macrolide in manure were 56.4%-94.6% with relative standard deviations (RSDs) of 2.6%-19.8%, the LODs (S/N=3) were 0.01-2.50 μg/kg, and the LOQs (S/N=10) were 0.05-7.90 μg/kg.The method was simple with high stability, high sensitivity and good reproducibility, and suitable for the simultaneously determination of many antibiotics in animal and poultry manure.

Survey of Package Inserts for Cautionary Statements about Hypersensitivity Caused by Drug Moieties Similar to Sulfonamide / 医薬品情報学

<b>Objective: </b>The aim of this study was to review cautionary statements regarding hypersensitivity to drugs with a moiety similar to sulfonamide on Japanese package inserts.<br><b>Methods: </b>From approved drugs listed as of March 2015, we selected those with a moiety similar to sulfonamide and examined their therapeutic categories, together with the presence or absence, location, and wording of cautionary statements regarding usage, and matters pertaining to a history of drug hypersensitivity that was not limited to sulfonamide, on the package inserts.<br><b>Results: </b>We extracted 73 drugs (65 components) that included a moiety similar to sulfonamide.  Their therapeutic categories were diverse, and 39 (53.4%) had cautionary statements about hypersensitivity caused by a moiety similar to sulfonamide.  Among these 39 drugs, the cautionary statements were located in different sections (Contraindication 31, Careful Administration 4, and Important Precautions 4).  The cautionary statements showed differences in wording according to the individual drugs or positions.  For 10 of the drugs, information pertaining to a history of drug hypersensitivity not limited to sulfonamide was provided.<br><b>Conclusion: </b>Medical staff should recognize that package inserts are not standardized with regard to cautionary statements about hypersensitivity caused by moieties similar to sulfonamide, and that it is necessary to predict or judge the likelihood of cross-hypersensitivity reaction to such moieties on the basis of their chemical structure.  In addition, it is necessary to carefully observe the clinical condition of individual patients who are receiving drugs that have a moiety similar to sulfonamide.

Synthesis of some novel enzyme inhibitors and antibacterial agents derived from 5-(1-(4-tosyl)piperidin-4-yl)-1, 3, 4-oxadiazol-2-thiol

ABSTRACT Keeping in mind the pharmacological importance of the 1,3,4-oxadiazole moiety, a series of new S-substituted derivatives, 5a-h, of 5-(1-(4-tosyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol (3) were synthesized. The reaction of p-toluenesulfonyl chloride (a) and ethyl isonipecotate (b) produced ethyl 1-(4-tosyl)piperidin-4-carboxylate (1) which was further transformed into 1-(4-tosyl)piperidin-4-carbohydrazide (2) by hydrazine hydrate in methanol. Compound 2 was refluxed with CS2 in the presence of KOH to synthesize 5-(1-(4-tosyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol (3). The desired compounds, 5a-h, were synthesized by stirring 3 with aralkyl halides, 4a-h, in DMF using NaH as an activator. The structures of synthesized compounds were elucidated by 1H-NMR, IR and EI-MS spectral studies. These compounds were further evaluated for enzyme inhibitory activity against lipoxygenase and alpha-glucosidase, along with antibacterial activity against Gram-negative and Gram-positive bacteria.

RESUMO Tendo em vista a importância farmacológica da porção 1,3,4-oxadiazol, sintetizou-se uma série de novos derivados S-substituídos, 5a-h, de 5-(1-(4-tosi)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). A reação do cloreto de p-toluenossulfonila (a), com isonipecotato de (b) etila forneceu 1-(4-tosil)piperidin-4-carboxilato de metila (1), que foi, em seguida, transformado em 1-(4-tosil)piperidin-4-carbo-hidrazida (2) por reação com hidrato de hidrazina em metanol. O composto 2 foi submetido a refluxo com CS2 na presença de KOH para se obter 5-(1-(4-tosil)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). Os compostos desejados, 5a-h, foram obtidos por agitação de 3 com haletos de aralquila, 4a-h, em DMF, na presença de NaH. As estruturas dos compostos sintetizados foram elucidadas através de análise dos espectros de 1H-MNR, IR e EI-MS. Estes compostos foram, ainda, avaliados quanto à inibição das enzimas lipoxigenase e alfa-glucosidase, juntamente com a atividade antibacteriana contra bactérias Gram positivas e Gram negativas.

Low-Dose Acetazolamide in the Treatment of Premenstrual Dysphoric Disorder: A Case Series

The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.

Characterization of antibiotic resistance in Salmonella enterica isolates determined from ready-to-eat (RTE) salad vegetables

In the last decade, ready-to-eat (RTE) salad vegetables are gaining increasing importance in human diet. However, since they are consumed fresh, inadequate washing during processing can bring on some foodborne illnesses, like salmonellosis, since these food items have natural contamination from soil and water. During 2009-2010, a total of 81 samples were purchased arbitrarily from local markets in Ankara, and were examined for Salmonella contamination. Salmonella screening was performed by using anti-Salmonella magnetic beads system and polymerase chain reaction (PCR) identification of the suspected colonies. Then, the antibiotic resistance profiles of four Salmonella strains identified (strains RTE-1, RTE-2, RTE-3, and RTE-4) were also investigated, since the mechanism by which Salmonella spp. have accumulated antibiotic resistance genes is of interest. All strains showed resistance against sulfonamides (MIC > 128 mg/L). Further results suggested that associated sulfonamide resistance genes were encoded by the 55.0 kb plasmid of strain RTE-1 that involves no integrons. As a result of using two primers (P1254 and P1283) in randomly amplified polymorphic DNA-PCR (RAPD-PCR) analysis, two common amplicons (364 bp and 1065 bp) were determined. The findings of this study provide support to the adoption of guidelines for the prudent use of antibiotics in order to reduce the number of pathogens present on vegetable and fruit farms. Besides, since it is shown that these bacteria started to gain resistance to antibiotics, it is necessary to further investigate the prevalence of them in foods.

Sulfanilamide desensitization treatment for systemic lupus erythematosus complicated with Pneumocystis pneumonia: a case report and case analysis / 中国药学杂志

OBJECTIVE: To report the clinical manifestations of one case systemic lupus erythematosus (SLE) complicated with Pneumocystis pneumonia(PCP), and the process that in accordance with the treatment guidelines of the patients who had a history of sulfa allergy in patients with sulfa desensitization program treatment. METHODS: Involved in the discussion of treatment of a patient in our hospitals intensive care unit who has systemic lupus erythematosus(SLE) complicated with Pneumocystis pneumonia(PCP) and history of sulfur allergy, and analyze the clinical data of the patient retrospectively. RESULTS: The middle-aged women suffering from systemic lupus erythematosus (systemic lupus erythematosus; SLE) combined Pneumocystis pneumonia (Pneumocystis pneumonia, PCP) infection. Due to her history of sulfa drug allergies, antibiotics and sulfa desensitization treatment were given. Symptoms were eased sputum smear PCP (negative). CONCLUSION: The infection is generally the main life-threatening reason to patients with autoimmune disease in clinical, taking a comprehensive treatment is a necessary measure for patients with SLE combined PCP for the patients who are allergic to Sulfa drugs with contraindications or undesirable effects using alternative drug. Desensitization treatment may be one of the choices for these patients. Copyright 2012 by the Chinese Pharmaceutical Association.

The Blocking of c-Met Signaling Induces Apoptosis through the Increase of p53 Protein in Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer. MATERIALS AND METHODS: The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry. RESULTS: SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein. CONCLUSION: Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer.

Cutaneous adverse reactions to sulfonamide antibiotics.

Background: Sulfonamides are divided into two main groups which are sulfonamide antibiotics and sulfonamide non-antibiotics. The wide use of sulfonamide antibiotics leads to increasing incidence of sulfonamide cutaneous reactions. Objective: The purpose of this study is to explore the cutaneous manifestations induced by sulfonamide antibiotics in a large number of Thai patients, including human immunodeficiency virus (HIV) and non-HIV infected individuals. The second purpose is to determine the risk factors for development of sulfonamide cutaneous reactions. Methods: We retrospectively studied 191 patients with sulfonamide antibiotics cutaneous reactions attending the adverse drug reaction center, Siriraj Hospital, Bangkok between 2006 and 2010. Results: Majority of the patients was female (59.7%).Maculopapular rash was the most common cutaneous manifestation (37.7%), followed by fixed drug eruption (22%), angioedema with or without urticaria (12.6%) and urticaria alone (12%). Among those with known HIV serology, maculopapular eruption occurred more frequently in the HIV positive group while fixed drug eruption occurred more frequently in HIV-negative group. Conclusion: From our study, there were no significant determination factors to develop serious drug reactions. However, the HIV-positive status and lower level of CD4 count had a tendency to increase risk of developing serious cutaneous reactions.

Synthesis and Spectroscopic Property of Acridinium-9-sulfonamides / 分析化学

By introducing an electro-withdrawing antipyrine group, N-(p-toluenesulfonyl)-N-(4-antipyrine)-10-methylacridinium-9-carboxamide triflate was prepared. The UV, FL and CL properties of the target compound and of its precursor were investigated by comparing with those of the model compound N-(p-toluenesulfonyl)-N-phenyl-10-methylacridinium-9-carboxamide triflate and the corresponding precursor respectively. The results show that acridine sulfonamide with a heterocyclic antipyrine group exhibits blue shift of both UV absorption and of maximum excitation wavelength(λex) and emission wavelength(λem) in FL spectra, comparing with the corresponding model compound. The λex of the final target and its precursor are 268 and 274 nm, respectively; and the λem are 321 and 327 nm, respectively, while λex of the model compound and its unmethylated precursor are 365 and 359 nm, respectively; and the λem are 504 and 440 nm, respectively. Moreover, the chemiluminescence of the final target compound triggered by H2O2 could finish within 1.1 s; and the quantum yield is similar to that of the model compound, being 5.6 times high as that of luminol.

Effects of Zinc and Hypothermic Process during the Light and Dark Adaptation of Vertebrate Retina

PURPOSE: The purpose of this study was to clarify the effects of zinc treatment and hypothermia on visual adaptation and visual sensitivity in bullfrogs (Rana catesbeiana), which are poikilothermal animals capable of adjusting quickly to environmental temperature changes. METHODS: The effects of both zinc treatment and hypothermia on visual sensitivity were studied by using electroretinogram (ERG) recording and absorption spectra scanning before and after zinc and TSQ (N-[6-methoxy-8-quinolyl]-p-toluene sulfonamide) treatment, with or without temperature changes. RESULTS: In spite of malnutrition due to hibernation, the optimal zinc concentration effect was obtained at 10-4 M (10-2 M 200 microliter ZnCl2 in 20 microliter Ringer's solution) according to ERG recording. After zinc treatment and hypothermia induction, increments of all ERG components and thresholds were taken by ERG recording. These results showed that both zinc treatment and hypothermia may increase visual sensitivity during visual adaptation. In spectral scans, the absorbance increment due to zinc treatment and hypothermia was shown over the whole spectral range (400~750 nm), and it was especially prominent at alpha-peak (about 500 nm). In addition, there was a decrease in absorption differences between dark adaptation and light adaptation after zinc treatment. Furthermore, according to the visual sensitivity decrement using TSQ as a zinc specific chelator, this visual sensitivity increase was shown to be caused by zinc. CONCLUSIONS: As the results suggest, both zinc treatment and hypothermic effects may improve visual sensitivity by promoting rhodopsin regeneration and inhibiting rhodopsin bleaching induced by light illumination. Zinc may activate the enzyme activity of retinol dehydrogenase and phosphodiesterase, while hypothermic effects may improve precursor transport, which is required for rhodopsin regeneration, by tightening membrane adhesion between retinas and retinal pigment epithelia. In addition, we believe that zinc treatment and hypothermic effects may work synergistically to accelerate visual sensitivity during visual adaptation.

Determination of Two Constituents in Compound Streptomycin Cream / 中国药房

OBJECTIVE:To determine streptomycin sulfate and sulfonamide in compound streptomycin cream by UV spectrophotometry.METHODS:The maltol-ammonium ferric sulfate colourimetry was adopted in which the ammonium ferric sulfate was taken as the developer,the absorbability of streptomycin sulfate was determined with the wavelength at521nm;The absorbability of sulfonamide was determined at a wavelength of251nm with0.1%mol/L NaOH taken as the sol-vent.RESULTS:The linear ranges of streptomycin sulfate and sulfonamide were200～950?g/ml(r=0.9994)and1.464～7.784?g/ml(r=0.9998)respectively;Their respective average recovery were99.1%(RSD=1.90%)and99.7%(RSD=1.60%).CONCLUSION:The method can be used as the quality control for compound streptomycin cream.

Determination of Glycyrrhizic Acid in Sulfonamide-glycyrrhiza Mixture by RP-HPLC / 中国药房

OBJECTIVE:To establish a RP-HPLC method for the determination of glycyrrhizic acid in sulfonamideglycyrrhiza mixture METHODS:Lichrosorb RPC18 analytical column was used The mobile phase was composed of methanol-(CH)4NH4OH(65∶35) The pH of the mobile phase was adjusted to 6 5 with 10% phosphoric acid Detection wavelength was 254nm RESULTS:Linearity was good in the range of 0 5～50?g/ml(r=0 9 996);the average recovery was 99 75%,RSD=1 87% CONCLUSION:The method is simple and convenient

Study on some sulfonamides utilized as drugs

From P-acctamino benzen sulfochlorua to P-acoltamino benzen sulfonamide to p- acctamido benzen sulfonylure to N1- n butyl, N2- sulfanilyure. This product is identical with carbutamide which pureed from Bucarban tablet (Hungary) in both infrared and melting point