The comprehensive effects of aluminum oxide nanoparticles on the physiology of freshwater microalga Scenedesmus obliquus and it's phycoremediation performance for the removal of sulfacetamide.

Nanoparticles are inevitable byproducts of modern industry. However, the environmental impacts arising from industrial applications of nanoparticles are largely under-reported. This study evaluated the ecotoxicological effects of aluminum oxide nanoparticles (Al2O3NP) and its influence on sulfacetamide (SA) biodegradation by a freshwater microalga, Scenedesmus obliquus. Although Al2O3NP showed limited toxicity effect on S. obliquus, we observed the toxicity attenuation aspect of Al2O3NP in a mixture of sulfacetamide on microalgae. The addition of 100 mg L-1 of Al2O3NP and 1 mg L-1 of SA reduced total chlorophyll by 23.3% and carotenoids by 21.6% in microalgal compared to control. The gene expression study demonstrated that ATPF0C, Lhcb1, HydA, and psbA genes responsible for ATP synthesis and the photosynthetic system were significantly downregulated, while the Tas gene, which plays a major role in biodegradation of organic xenobiotic chemicals, was significantly upregulated at 1 and 100 mg L-1 of Al2O3NP. The S. obliquus removed 16.8% of SA at 15 mg L-1 in 14 days. However, the removal was slightly enhanced (18.8%) at same concentration of SA in the presence of 50 mg L-1 Al2O3NP. This result proves the stability of sulfacetamide biodegradation capacity of S. obliquus in the presence of Al2O3NP co-contamination. The metabolic analysis showed that SA was degraded into simpler byproducts such as sulfacarbamide, sulfaguanidine, sulfanilamide, 4-(methyl sulfonyl)aniline, and N-hydroxy-benzenamine which have lower ecotoxicity than SA, demonstrating that the ecotoxicity of sulfacetamide has significantly decreased after the microalgal degradation, suggesting the environmental feasibility of microalgae-mediated wastewater technology. This study provides a deeper understanding of the impact of nanoparticles such as Al2O3NP on aquatic ecosystems.

Synthesis, characterization, theoretical prediction of activities and evaluation of biological activities of some sulfacetamide based hydroxytriazenes.

Six new N [(4-aminophenyl)sulfonyl]acetamide based hydroxytriazenes have been synthesized and characterized using elemental analysis, IR, 1H NMR, 13C NMR and MASS spectral analysis. Further, their theoretical predictions for probable activities have been taken using PASS (Prediction of Activity Spectra for Substance). Although a number of activities have been predicted but specifically anti-inflammatory, antiradical, anti-diabetic activities have been experimentally validated which proves that theoretical predictions agree with the experimental results. The object of the Letter is to establish Computer Aided Drug Design (CADD) using our compounds.

Death inducing and cytoprotective autophagy in T-47D cells by two common antibacterial drugs: sulphathiazole and sulphacetamide.

The broad spectrum of the pharmacological effects of sulphonamide family of drugs motivated us to investigate the cellular mechanisms for anti-cancer effects of sulphathiazole and sulphacetamide on T-47D breast cancer cells. Fluorescent microscopy, flow cytometric analysis, caspase-3 activity and DNA fragmentation assays were used to detect apoptosis. The distribution of the cells among different phases of the cell cycle was measured by flow cytometry. The expression of several genes with important roles in some critical cellular pathways including apoptosis, mTOR/AKT pathway and autophagy were determined by real-time RT-PCR analysis. Sulphathiazole and sulphacetamide induced anti-proliferative effects on T-47D cells were independent of apoptosis and cell cycle arrest. The overexpression of critical genes involved in autophagy including ATG5, p53 and DRAM indicated that the main effect of the drug-induced anti-proliferative effects was through induction of autophagy. This process was induced in two different forms, including death inducing and cytoprotective autophagy. Sulphathiazole treatment was followed by higher expression of p53/DRAM and downregulation of Akt/mTOR pathway resulting in death autophagy. In contrast, sulphacetamide treatment lowered expression of p53/DRAM pathway in parallel with upregulation of Akt/mTOR pathway promoting cytoprotective autophagy. The results indicated that autophagy is the main mechanism mediating the anti-cancer effects of sulphathiazole and sulphacetamide on T-47D cells. Alignment of the p53 and DRAM expression along with activation level of Akt survival pathway therefore determines the type of autophagy that occurs.

Genetic variability of enterobacterial resistant integrons.

Sulfamide-resistant (SulR) natural strains of enterobacteria (11.9% of a total of 797 cultures, isolated with enteric microflora of honeybee gut, bee-fermented pollen, and plant issues) were tested for class 1 antibiotic resistance integrons (MRI). Only 5.3% of SulR strains were MRI-positive. Mutability of weak (wild type) MRI promotor has been shown. A more active hybrid promotor type has been amplified in isolated Klebsiella oxytoca strains. Regulatory genetic modifications in MRI are fraught with the development of multiple drug resistance of opportunistic strains.

Researches concerning the synthesis and antituberculosis action of some new sulphacetamide derivatives.

In the present study we emphasized the antituberculosis action of new sulphacetamide derivatives. In order o extend the research for obtaining antituberculosis substances, we decided to study the influence of the introducing of the thiourea and sulphamide groups in the molecule on the antituberculosis activity of the Isoniazid. We have developed a simple and precise method for obtaining the thiourea derivatives of sulphamides' isonicotinoilhydrazone. The structure of the newly synthesized compounds was confirmed by the quantitative elemental analysis as well as IR spectral measurements. We tested the antituberculosis action of new eight obtained sulphacetamide derivatives. Testing new substances on the Mycobacterium tuberculosis complex implies the insemination of inoculums on tubes containing the new substances, in chosen concentrations. Early tests on Mycobacterium tuberculosis strains show susceptibility to these new compounds (for the tested concentrations). The new compounds represent a premise for obtaining new antimycobacterial agents.

Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters. Characterization of reaction products and proposed mechanism of action.

The synthesis and antiviral properties of pyridinioalkanoyl thioester (PATE) compounds that target nucleocapsid p7 protein (NCp7) of the human immunodeficiency virus type 1 (HIV-1) have been described previously (Turpin, J. A., Song, Y., Inman, J. K., Huang, M., Wallqvist, A., Maynard, A., Covell, D. G., Rice, W. G., and Appella, E. (1999) J. Med. Chem. 42, 67-86). In the present study, fluorescence and electrospray ionization-mass spectrometry were employed to determine the mechanism of modification of NCp7 by two lead compounds, N-[2-(5-pyridiniovaleroylthio)benzoyl]sulfacetamide bromide and N-[2-(5-pyridiniovaleroylthio)benzoyl]-4-(4-nitrophenylsulfonyl )anili ne bromide (compounds 45 and 47, respectively). Although both compounds exhibit antiviral activity in cell-based assays, we failed to detect appreciable ejection of zinc from NCp7 under conditions in which previously described NCp7-active disulfides readily eject zinc. However, upon "activation" by Ag(+), compound 45 reacted with NCp7 resulting in the zinc ejection from both zinc fingers. The reaction followed a two-step mechanism in which zinc was ejected from the carboxyl-terminal zinc finger faster than from the amino-terminal zinc finger. Both compounds covalently modified the protein with pyridinioalkanoyl groups. Compound 45 modified cysteines 36 and 49 of the carboxyl-terminal zinc finger. The results obtained herein demonstrate that PATE compounds can be constructed that selectively target only one of the two zinc fingers of NCp7, thus providing an impetus to pursue development of highly selective zinc finger inhibitors.

The Guinea Pig Blinking Test: a comparison with human responses.

The Guinea Pig Blinking Test (2) was presented as a model for the selection and development of comfortable ocular formulations. This study compares human nociceptive responses and the blinking response of the guinea pig to different concentrations of a topically applied ophthalmic drug, sulfacetamide. The number of human subjects noting pain upon instillation of various concentrations of sulfacetamide (3) was compared to the blinking responses of guinea pigs treated with 2.5%-17.5% sulfacetamide. The number of blinks was counted over a period of 5 minutes following (1) saline (0.9% NaCl), and (2) 30-60 minutes later a test solution. A Blinking Index (B.I.) = blinks drug/blinks saline was calculated for each animal. The dose/response curves of both humans and guinea pigs were almost identical, showing a threshold at 5% sulfacetamide, followed by a linear increase, reaching a maximum at 12.5%-15% sulfacetamide. A 2.5% solution that elicited pain in 10% of human subjects yielded a B.I. = 1.04 +/- 0.05, whereas a 12.5% solution that elicited pain in 95% of human subjects yielded a B.I. = 1.61 +/- 0.13 (mean +/- S.E., n = 10, P < 0.05). The strong linear relationship between the guinea pig blinking response and the human perception of pain, following identical treatment with a topical ophthalmic drug, demonstrates that this animal test can be useful in predicting the degree of ocular discomfort of human subjects.

Synthesis and spectroscopy studies of copper(II) nitrate of sulfacetamide drug. Crystal structure of [Cu(sulfacetamide)2(NO3)2]. Antibacterial studies.

The structural spectroscopic, and thermal properties of a complex of sulfacetamide (Hsacm) with Cu(II) have been investigated. The complex [Cu(Hsacm)2(NO3)2] crystallizes in the monoclinic system, space group P2(1)/n. The cell dimensions are a = 7.696(7) A, b = 8.017(7) A, c = 19.230(10), beta = 110.80(1) degree, V = 1109(1) A3, Z = 2, and Dx = 1.84 g/cm3. The structure was refined to R = 0.0776. Cu(Hsacm)2(NO3)2 molecules form a long polymeric chain extended along the b-axis. The copper(II) coordinated geometry is tetragonally distorted octahedral with two amino nitrogens from Hsacm and two oxygens from nitrato anions in the basal plane and two acetamido oxygens from neighbor Hsacm molecules in the apical position. Each sulfacetamide, acting as a bidentate ligand, links two Cu(II) ions as a bridge through the Namino and the Oacetamido atoms. The complex proved to possess higher bacteriostatic activity than the corresponding ligand.

Mode of action of the antifertility sulphonamides: lack of effects on folate metabolism.

The effects of some antifertility sulphonamides on folate metabolism were investigated in the male rat. Subcutaneous injections of sulphanilamide at a dose of 150 mg/kg/day for 6 weeks produced a marked reduction in fertility of the treated animals. This effect was rapidly recovered by one week after drug withdrawal. Similar treatments with trimethoprim (30 mg/kg/day) or pyrimethamine (8 mg/kg/day) had virtually no effect on fertility. The synergistic effect of trimethoprim or pyrimethamine on the antifertility activity of sulphanilamide was not observed when the drugs were administered in combinations. Treatment with sulphapyridine (450 mg/kg/day for 6 weeks) failed to alter the levels of folate in the blood and the reproductive organs except the testes in which accumulation of folic acid occurred. The results suggest that the antifertility activity of sulphanilamide, sulphapyridine and perhaps some other sulphonamides is not associated with the inhibition of folate metabolism.

Rat bioassay of wheat bran folate and effects of intestinal bacteria.

This study estimates the folate endogenous to a food material (wheat bran) and examines the role of intestinal bacteria in the rat bioassay for folate. After a 4-wk folate depletion period, rats were fed for an additional 4 wk basal diets with or without 0.5% phthalylsulfacetamide and with 100, 200 or 300 g of wheat bran; or 50, 100 or 150 g of xylan; or 0, 0.25, 0.50 or 0.75 mg of folic acid added per kg of basal diet. Xylan increased both liver and fecal folate, and this effect was nearly eliminated by phthalylsulfacetamide. Wheat bran contributed 1.6 micrograms of available folate per g of wheat bran without phthalylsulfacetamide in an apparently valid slope-ratio analysis. With the addition of phthalylsulfacetamide, liver folate increased in rats fed wheat bran diets and decreased in rats fed folic acid diets. The slope-ratio analysis for wheat bran folate with phthalylsulfacetamide became invalid due to a lack of intersection. Phthalylsulfacetamide had no effect on fecal folate excretion from rats fed the wheat bran diets. Further studies are needed on a variety of foods with and without phthalylsulfacetamide to evaluate the effect and importance of intestinal folate synthesis in the rat.

Influence of drug vehicle on ocular contact time of sulfacetamide sodium.

Sulfacetamide sodium drops and ointments were applied to the conjunctiva of patients and volunteers. Tear samples were taken and analyzed for sulfacetamide sodium content. The minimal inhibitory concentrations of the drug in para-aminobenzoic acid-free media were determined to be between 20 and 50 micrograms/mL against Escherichia coli and Staphylococcus aureus, and the effective concentrations of the sulfa were taken as 50 micrograms/mL. The concentration of sulfacetamide sodium in tears fell to the 50 micrograms/mL level in 30 minutes, two hours, and five and a half hours after the single application of 10 microL of 15% and 30% drops and 25 microL of all three ointments, respectively. The ocular contact time of the sulfa was increased by increasing the concentration of drug. The makeup of the three ointments differed greatly, yet the ocular contact time was similar.

The effect of sodium sulphacetamide and sodium mandelate in brilliant green agar on the growth of salmonellas.

An assessment was made of the ability of 425 isolates of salmonellas, belonging to 54 serotypes, to grow on seven selective media. Several isolates of Salmonella dublin and Salm. paratyphi B failed to grow on brilliant green agar supplemented with sodium sulphacetamide and sodium mandelate. On this medium the colonies of 30 isolates which were able to grow were extremely small after 20 h incubation, and consequently their recognition was difficult. The sodium sulphacetamide was responsible for the reduction in colony size.

Effect of 30% sodium sulfacetamide on corneal sensitivity.

This study compares the effect of 10 and 30% sodium sulfacetamide on corneal sensitivity. The corneal sensitivity was measured on 11 subjects with a Cochet -Bonnet aesthesiometer without any drug, 10 and 30% sodium sulfacetamide . The results obtained for the mean corneal sensitivities (mean +/- standard error) for the control, 10 and 30% sodium sulfacetamide were 1.07 +/- 0.025, 1.09 +/- 0.023, and 1.36 +/- 0.10 gm/mm2, respectively. We found that there was no statistical difference between the control value and 10% sodium sulfacetamide , but the 30% produced a significant decrease in corneal sensitivity when compared to the control and 10% concentration.

Effects of preservatives, steroids, and ethylenediaminetetraacetate on the antimicrobial activity of sulfacetamide.

The effect of EDTA (ethylenediaminetetraacetate), steroids, and preservatives on the antimicrobial activity of 10% sodium sulfacetamide solutions was evaluated in this study by kill rate and minimum inhibitory concentration (MIC) using five representative microorganisms. The results indicate that thimerosal-preserved sulfacetamide solutions containing EDTA are more effective against Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus epidermidis, and Candida albicans than similar paraben-preserved solutions. Furthermore, the addition of EDTA improves the kill rate, but not the MIC, for the Pseudomonas, Serratia, and Candida species regardless of the preservative. The combination of a steroid with sulfacetamide does not affect its antimicrobial activity.

In vitro susceptibility of Gardnerella vaginalis and Bacteroides organisms, associated with nonspecific vaginitis, to sulfonamide preparations.

Recent reports suggest that anaerobic Bacteroides organisms are frequently found with Gardnerella vaginalis in nonspecific vaginitis. Specimens taken from 96 women with vaginal discharge were tested simultaneously for these organisms. G. vaginalis was found in 73% of the specimens, Bacteroides was found in 53%, and both organisms were found in 47%. Sulfonamides have been widely used in the successful treatment of vaginitis. Paradoxically, G. vaginalis is reported to be resistant, and it has been suggested that it could be the vehicle of the drugs which effects the cure. Little is known of the susceptibility of vaginal anaerobes to the sulfonamides. G. vaginalis and Bacteroides isolates were therefore tested in vitro against the individual excipients of sulfonamide tablets, and minimal inhibitory concentration tests were also performed against the three active drugs. The excipients had no effect on G. vaginalis, but Bacteroides strains were susceptible to the urea component. All strains of both organisms were susceptible to at least two of the three sulfonamides at high concentrations.

[Effect of tranquilizers and analgesics on the permeability of the histohematic barriers for sulfacyl in inflammation]. / Vliianie trankvilizatorov i anal'getikov na pronitsaemost' gisto-gematicheskikh bar'erov dlia sul'fatsila v usloviiakh vospaleniia

The effect of neurotropics (analgetics and tranquilizers) on the permeability of histo-blood barriers in normalcy and pathology was wound to be dissimilar. In tests conducted on intact rats the studied neurotropic agents used in pharmacological doses did not affect the permeability of the histological-blood barriers of the brain and spleen with respect to the indicator--sodium sulfacyl. In rats with an inflammation focus the same drugs produced changes of the said factor, not always similar in their orientation (rise of fall).