Cumulative Toxicity of Residue Degradation Products of Penicillin Bacteria

[Objective] The research aimed to discuss the accumulation of toxic slag of penicillin bacteria residue degradation products and explore its ability to meet the aquaculture industry as a protein feed into development and utilization conditions.[Method] Through the sub-acute toxicity tests in mice strains,which were fed by different doses of penicillin bacteria residue degradation products （3% and 6%） under continuous observation of 15 weeks,recording a weekly mouse weight and death,and sampling executed after the test,animal liver and kidney function were blood test,taking heart,liver,spleen,kidney weighing,as well as liver and kidney pathology observed in the optical microscope.[Result] There were no significant differences （P 0.05） between the test group mice body weight,mortality and liver and kidney function and the control group within 15 weeks.Low-dose test group could be seen the liver cells,renal tubular epithelial nuclei broken,and a small number of liver and kidney cells with mild edema.High-dose test group could be seen in liver tissue of mice nuclei fragmentation and a fat droplets,the majority of liver cells,edema,and only a small number of liver cells,there were no significant changes.Renal portal area showed inflammatory cell infiltration,renal tubular epithelial cells,edema and necrosis.[Conclusion] In this experimental condition,the degradation products of penicillin bacteria residue played a mild toxcity on organ parenchymal cells in mice.

Effects of Stylosanthes scabra Forage Supplementation on in Vitro Gas Production and Fiber Degradation of Eragrostis Grass Hay

Natural pastures constitute a major component of ruminant livestock feed, and are the most cost-effective feed resource available for smallholder subsistence farmers. However, this feed resource does not meet animal nutritional requirement due to deficiency in nitrogen, energy and minerals. In addition, at maturity lignification is the major concern since it reduces digestibility and contributes to methane emission. Thus, the objective of this study was to evaluate the effect of supplementing low-quality Eragrostis grass hay with five (9281, 11,252, 11,255, 11,595 and 11,604) selected Stylosanthes scabra accessions on in vitro ruminal fermentation and neutral detergent fiber degradation. Therefore, in vitro study was conducted on grass hay, accessions and the mixture of grass hay with each accession included at two (15%, 30%) levels. The substrates (grass hay, accessions and the mixtures) were incubated in separate serum bottles for 72 h. Neutral detergent fiber (NDF) of the accessions ranged from 300 to 350 g/kg DM with crude protein (CP) value ranging from 177.5 to 184.1 g/kg DM. Eragrostis grass hay had NDF value of 813 g/kg DM, with CP value of 34.3 g/kg DM. Grass hay fermented slowly, it took 30 h for grass hay to produce gas volume above 50 mL, while Stylosanthes scabra accessions took 12 h. Supplementing grass hay with accessions significantly improved fermentation. However, it was observed that 15% inclusion took 30 h to produce gas volume above 50 mL, whereas at 30% inclusions it took 24 h for accession 9281, 11,595 and 11,604. Accession 11,604 improve grass fermentation by almost three times the value of grass hay in 2 h. Grass hay supplemented with accession 11,604 at 30% had a positive associative effect and significantly improved NDF degradability. In conclusion, accession 11,604 may be fed strategically as forage supplement to low-quality forage for ruminants.

Identification of Oxidative Degradation Products of Lansoprazole by Using High Resolution Mass Spectrometry Spectral Data

The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution mass spectrometer (HRMS) was used for identification of oxidative degradation impurities (DIs) of lansoprazole. The utilization of HRMS facilitates to determine the accurate mass of impurities and their fragment/product ions. A fast mass spectrometer (MS) compatible reverse phase chromatography method was used to investigate the oxidative stressed impurities. HPLC column;C18 (50 × 4.6 mm, 3.5 μm) was used with gradient elution. Spectral data acquired using information dependent acquisition (IDA) with real time dynamic background subtraction algorithm (DBS). Three oxidative impurities: DI-I (m/z 386.0781), DI-II (m/z 402.0734) and DI-III (m/z 386.0785), was observed during this study;interpretation of high resolution spectral data of all three impurities was carried out;elemental composition and molecular structure was proposed for major fragments. In this study mass error was found ≤7.7 parts per million (ppm).

Degradation rates and products of fluticasone propionate in alkaline solutions

The apparent degradation rate constant of fluticasone propionate(FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169 ± 0.003 h^(-1), and four degradation products(products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH_3CN=1:1 were 0.472 ± 0.013 h^(-1) and 0.154 ± 0.000 h^(-1)(n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance(NMR)and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH_3CN=1:1 was found to be product 2 based on ~1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

Drug stability is closely related to drug safety and needs to be considered in the process of drug production,package and storage.To investigate the stability of epalrestat,a carboxylic acid derivative,a reversed-phase high-performance liquid chromatography(RP-HPLC)method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions,such as different pH,temperatures,ionic strengths,oxidation and irradiation.The calibration curve was A=1.6×10^5C–1.3×10^3(r=0.999)with the liner range of 0.5–24μg/mL,the intra-day and inter-day precision was less than 2.0%,as was the repeatibility.The average accuracy for different concentrations was more than 98.5%,indicating that perfect recoveries were achieved.Degradation kinetic parameters such as degradation rate constants(k),activation energy(Ea)and shelf life(t0.9)under different conditions were calculated and discussed.The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however,it was more stable in neutral and alkaline conditions as well as lower temperatures.The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics.Furthermore,the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS,with seven degradation products being detected and four of them being tentatively identified.

A stability-indicating LC–MS/MS method for zidovudine: Identification,characterization and toxicity prediction of two major acid degradation products

Zidvovudine(AZT) is a nucleoside analogue reverse transcriptase inhibitor(NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C_(18) column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectrometry(LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H]^+ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography(HPLC) using Waters XBridge Prep C_(18)(250 mm×10 mm, 5 μm).Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2(R1).

Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH（1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0） and temperature（0, 25, 37 and 45 °C）. The linear range was 0.5–25 μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 k J/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.

Gaseous products generated by radiation degradation of N,N-diethylhydroxylamine aqueous solution

In this paper,gaseous products generated by radiation degradation of N,N-diethylhydroxylamine (DEHA) in aqueous solution are studied.The results show that by 10～1000 kGy irradiation of the solution in DEHA concentration of 0.1～0.5 mol·L^(-1),the gaseous products were mainly hydrogen,methane,ethane and ethene.The volume fraction of hydrogen did not change much with different concentrations of DEHA.The volume fraction of methane and ethane decreased,but that of ethene increased,with increasing DEHA concentration.The volume fraction of hydrogen,methane and ethane increased with the dose.The relationship of the volume fraction of ethene with the dose had something to do with the DEHA concentration.

Photoelectrocatalytic Oxidation of Ethinylestradiol on a Ti/TiO₂Electrode: Degradation Efficiency and Search for By-Products

The degradation of ethinylestradiol (EE, an orally bio-active estrogen) in an aqueous-methanolic solution using a Ti/TiO2 thin-film electrode and UV radiation (a photoelectrocatalytic system) was evaluated. Hence, HPLC/UV analysis shows that EE (at 0.34 mmol) is totally consumed after 30 minutes of exposure to the photoelectrocatalytic system in the presence of Na2SO4 (0.1 mol·L-1) and with an applied bias potential of +1.0 V versus the Ag/AgCl reference electrode. Moreover, monitoring by direct infusion electrospray ionization mass spectrometry (ESI-MS) and SPME-GC/ MS (solid phase microextraction coupled with gas chromatography-mass spectrometry) reveals that apparently no degradation products are formed under these conditions. Hence, this study demonstrates that the photoelectrocatalytic system can be efficiently used to promote the complete degradation (and likely mineralization) of this hormone under these conditions.

Keratinase production and keratin degradation by a mutant strain of Bacillus subtilis

A new feather-degrading bacterium was isolated from a local feather waste site and identified as Bacillus subtilis based on morphological, physiochemical, and phylogenetic characteristics. Screening for mutants with elevated keratinolytic activity using N-methyl-N＇-nitro-N-nitrosoguanidine mutagenesis resulted in a mutant strain KD-N2 producing keratinolytic activity about 2.5 times that of the wild-type strain. The mutant strain produced inducible keratinase in different substrates of feathers, hair, wool and silk under submerged cultivation. Scanning electron microscopy studies showed the degradation of feathers, hair and silk by the keratinase. The optimal conditions for keratinase production include initial pH of 7.5, inoculum size of 2% （v/v）, age of inoculum of 16 h, and cultivation at 23 ℃. The maximum keratinolytic activity of KD-N2 was achieved after 30 h. Essential amino acids like threonine, valine, methionine as well as ammonia were produced when feathers were used as substrates. Strain KD-N2, therefore, shows great promise of finding potential applications in keratin hydrolysis and keratinase production.

Effect of lactic acid bacteria inoculants on alfalfa(Medicago sativa L.) silage quality:assessment of degradation(in situ) and gas production(in vitro)

Alfalfa （Medicago sativa） is difficult to ensile successfully because of the low content of moisture and water-soluble carbohydrates （WSC） in fresh alfalfa and the high buffering capacity in fresh alfalfa. Here, we conducted a study to evaluate the effects of three lactic acid bacteria （LAB） inoculants （Lactobacillus case/, lactobacillus plantarum, and Pediococcus pentosaceus） on silage quality, in sitE/ruminal degradability, and in vitro fermentation of alfalfa silage. The first cut of alfalfa was wilted, chopped, and randomly divided into four groups： the control （CON） and control mixed with three separate LAB inoculants （106 cfu g-1）. Simmental steers with a body weight of （452±18） kg and with installed rumen fistulas were prepared for in situ degradation and for in vitro gas production. LAB inoculants had a lower （P〈0.05） content of butyric acid than the CON group. Among them, the L. casei inoculated silage had a higher （P〈0.05） content of water-soluble carbohydrate （WSC） and a lower （P〈0.05） NH3-H content. The effective degradation （ED） of crude protein in LAB inoculation decreased （P〈0.05）, while the ED of acid detergent fiber increased （P〈0.05） in situ fermentation. The alfalfa silage with LAB inoculants produced more carbon dioxide （P〈0.05）. The NH3-H content of mixed incubation fluid in L. casei inoculated silage was lower （P〈0.05） compared with other groups. Therefore, this study showed that LAB inoculants could improve both ensiling quality and degradation. In particular, the L. casei inoculations exhibited better performance by limiting proteolysis during ensiling.

Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLC-UV method for their quantification

Leflunomide （LLM） is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A（R2）. In total, four degradation products （I-IV） were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions. LLM and all degradation products were optimally resolved by gradient elution over a C18 column. The major degradation product （IV） formed in hydrolytic alkaline conditions was isolated through column chromatography. Based on its IH NMR, IR and mass spectral data, it was characterized as a British Pharmacopoeial impurity B. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged and robust for quantification of LLM as well as product IV. Finally, the method was applied to stability testing of the commercially available LLM tablets.

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury

BACKGROUND: There have been few reports on the clinical significance of the fibrinogen degradation product(FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical signifi cance of the FDP level.METHODS: From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups: a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/m L, and a FDP≤100 group.RESULTS: The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score(ISS), volume of transfusion and mortality ratio in the FDP>100 group were signifi cantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS(R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency.CONCLUSION: The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

Molecular mechanism of the inhibition effect of Celecoxib on corneal collagen degradation in three dimensions

AIM: To clarify the molecular mechanism of Celecoxib on corneal collagen degradation and corneal ulcer. METHODS: Rabbit corneal fibroblasts were harvested and suspended in serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal fibroblast suspension were mixed on ice. The resultant mixture solidify in an incubator, after which test reagents and plasminogen was overlaid and the cultures were returned to the incubator. The supernatants from collagen gel incubations were collected and the amount of hydroxyproline in the hydrolysate was measured. Immunoblot analysis of MMP1, 3 and TIMP1, 2 was performed. MMP2, 9 was detected by the method of Gelatin zymography. Cytotoxicity Assay was measured. RESULTS: Celecoxib inhibited corneal collagen degradation in a dose and time manner; Celecoxib inhibited the IL-1 beta induced increases in proMMP1, 2, 3, 9 and active MMP1, 2, 3, 9 in a concentration-depended manner. Celecoxib can also inhibit the IL-1 beta induced increases in the TIMP1, 2. CONCLUSION: Celecoxib can inhibit corneal collagen degradation induced by IL-1 beta, this effect is the consequence of the reduction of MMP1, 2, 3, 9 and TIMP1, 2. The results of the present study provide new insight into Celecoxib in cornela ulcer treatment.

Ti_(3)C_(2) MXene co-catalyst assembled with mesoporous TiO_(2) for boosting photocatalytic activity of methyl orange degradation and hydrogen production

Photocatalytic degradation and hydrogen production using solar energy through semiconductor photocatalysts are deemed to be a powerful approach for solving environmental and energy crisis.However,the biggest challenge in photocatalysis is the efficient separation of photo-induced carriers.To this end,we report that the mesoporous TiO_(2)nanoparticles are anchored on highly conductive Ti_(3)C_(2)MXene co-catalyst by electrostatic self-assembly strategy.The constructed mesoporous TiO_(2)/Ti_(3)C_(2)composites display that the mesoporous TiO_(2)nanoparticles are uniformly distributed on the surface of layer structured Ti_(3)C_(2)nanosheets.More importantly,the as-obtained mesoporous TiO_(2)/Ti_(3)C_(2)composites reveal the significantly enhanced light absorption performance,photo-induced carriers separation and transfer ability,thus boosting the photocatalytic activity.The photocatalytic methyl orange degradation efficiency of mesoporous TiO_(2)/Ti_(3)C_(2)composite with an optimized Ti_(3)C_(2)content(3 wt%)can reach 99.6%within 40 min.The capture experiments of active species confirm that the·O_(2)-and·OH play major role in photocatalytic degradation process.Furthermore,the optimized mesoporous TiO_(2)/Ti_(3)C_(2)composite also shows an excellent photocatalytic H2 production rate of 218.85μmol g^(-1)h^(-1),resulting in a 5.6 times activity as compared with the pristine mesoporous TiO_(2)nanoparticles.This study demonstrates that the MXene family materials can be applied as highly efficient noble-metal-free co-catalysts in the field of photocatalysis.

Design of metal-organic frameworks(MOFs)-based photocatalyst for solar fuel production and photo-degradation of pollutants

Metal organic frameworks(MOFs)is a research hotspot in the solar fuel production and photo-degradation of pollutants field due to high surface area,rich metal/organic species,large pore volume,and adjustability of structures and compositions.Therefore,in this review,we first summarized the design factors of photocatalytic materials based on MOF from the perspective of"star"MOF.The modification strategies of MOFs-based photocatalysts were discussed to improve its photocatalytic activity and specific applications were summarized as well,including photocatalytic CO_(2)reduction,photocatalytic water splitting and photo-degradation of pollutants.Finally,the advantages and disadvantages of MOFs-based photocatalysts were discussed,the current challenges were highlighted,and suggestions for future research directions were proposed.

Monoclinic KNbO3 Nanowires for Photocatalytic Methane Production and Dye Degradation

The room temperature stabled monoclinic KNbO3 nanowires were found to act as photocatalyst for photocatalytic methane production and dye degradation in this work. Higher activities have been observed for monoclinic phase compared to the reference（orthorhombic phase）. In the photoreduction of CO2 reaction, the monoclinic KNbO3 nanowires exhibited a CH4 evolution rate of 0.025 μmol·g-1·h-1, which was higher than 0.021 μmol·g-1·h-1 of orthorhombic KNbO3 nanowires. In the photodegradation of rhodamine B（Rh B）, almost all the Rh B were degraded after 90 min light illumination for monoclinic KNbO3 nanowires. But for orthorhombic KNbO3 nanowires, the concentration of Rh B only decreased to 62% of the initial value.

Solvothermal fabrication of Bi_(2)MoO_(6) nanocrystals with tunable oxygen vacancies and excellent photocatalytic oxidation performance in quinoline production and antibiotics degradation

Novel Bi_(2)MoO_(6) nanocrystals with tunable oxygen vacancies have been developed via a facile low-cost approach with the assistance of a glyoxal reductant under solvothermal conditions.With the introduction of oxygen vacancies,the optical absorption of Bi_(2)MoO_(6) is extended and its bandgap narrowed.Oxygen vacancies not only lead to the appearance of a defect band level in the forbidden band but can also result in a minor up-shift of the valence band maximum,promoting the mobility of photogenerated holes.Moreover,oxygen vacancies can act as electron acceptors,temporarily capturing electrons excited by light and reducing the recombination of electrons and holes.At the same time,oxygen vacancies help to capture oxygen,which reacts with the captured photogenerated electrons to generate more superoxide radicals(·O_(2)-)to participate in the reaction,thereby significantly promoting the redox performance of the photocatalyst.From Bi_(2)MoO_(6) containing these oxygen vacancies(OVBMO),excellent photocatalytic performance has been obtained for the oxidation of 1,2,3,4-tetrahydroquinoline to produce quinoline and cause antibiotic degradation.The reaction mechanism of the oxidation of 1,2,3,4-tetrahydroquinoline to quinoline over the OVBMO materials is elucidated in terms of heterogeneous Catal.via a radical pathway.

Voltammetric Behavior of Degradation Product and Determination of Cefdinir

The electrochemical behavior of the degradation product of cefdinir（CDR） was studied in a 0.05 mol/L NaOH solution by means of linear sweep voltammetry（LSV） and cyclic voltammetry（CV）. The results indicate that the C=N bond in the oxime group was reduced. Moreover, a saturated adsorption amount of 1.32× 10^-10 mol/cm2 at Hg electrode was obtained. The adsorption coefficient β was 1.56× 10^5 L/mol. Gibbs standard energy of adsorption AGO at 25 ℃ was -29.63 kJ/mol and the number of electrons transferred n was 2. A method for the determination of CDR was proposed by differential pulse voltammetry（DPV）. The reduction peak currents of the CDR＇s degradation product were found to be linear in a concentration range of 4.0×10^-7--4.0×10^- 6 mol/L and that of 4.0× 10^-8-4.0× 10^-7 mol/L, respectively. The detection limit was found to be 3.0× 10^-8 mol/L under the optimized conditions. The applica- bility of this approach was illustrated by the determination of CDR in capsules. In addition, the mechanism about the degradation of CDR in 0.2 mol/L NaOH was discussed by UV spectrophotometry.

Degradation Dynamics of Pyrethroids in Cigarette Production Environment

[ Objective] In order to provide a reference for safe and reasonable use of pyrethroids in cigarette production, the degradation behaviors of three kinds of pyrethroids in cigarette production environment were studied. [ Method ] Three kinds of pyrethroids （permethrin, cyfluthrin and c/s-cypermethrin） were adminis- trated to two media （cut tobacco and iron sheet surface） in cigarette production environment at MRLs concentration, and the first sampling was conducted at 24 d post administration. Afterwards, sampling was performed once every 7 d, with a total of six times. The degradation rates of insecticides in different media were cal- culated, and degradation models were established. [ Result ] The contents of three kinds of insecticides in two media gradually declined with the prolongation of time, and degradation rates presented the trend of fast-slow-fast ; the degradation rates of permethrin, cyfluthrin and c/s-cypermethrin in cut tobacco at 36 d post ad- ministration were 97.14%, 88.89% and 95.38%, respectively; the degradation rates on iron sheet surface were 29.95%, 48.99% and 40. 24%, respectively. The half lives of three kinds of insecticides in cut tobacco were 1 -2 d, while those on iron sheet surface were 6 - 10 d. [ Conclusion] The contents of three kinds of insecticides in two media gradually declined with the prolongation of time, and their degradation regularity accorded with first order kinetic equation.