HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins

Background Because of the pivotal role of the human leukocyte antigen （HLA） class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies （4 major and 4 minor antigenic determinants） in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some （113 patients and 87 healthy control subjects） were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria （P = 0.011; P = 0.019; P = 0.005 respectively）. Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group （P = 0.024; P = 0.038; P = 0.038）. A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not （X^2 = 5.134, P = 0.023）, and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl （PVA, X^2 = 4.057, P = 0.044）.Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.

SYNTHESIS, STRUCTURE AND ANTI-RESISTANT BACTERIAL ACTIVITY OF COMPLEXES OF PENICILLINS WITH METAL IONS

Many metal ions can influence the stability, distribution and metabolic ways and hence the activity of drugs in human body. Penicillins are a sort oF β-lactam drugs which have important prospects. That some metal ions such as Zn(Ⅱ) and Cu(Ⅱ) can remarkably catalize hydrolysis of penicillins involves not only stability but

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori:A retrospective single center study

BACKGROUND Although highly effective as a component of Helicobacter pylori(H.pylori)treatment regimen,tetracycline is associated with a high incidence of medicationrelated adverse events.Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates.AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients(10/2020-12/2021)who received tetracycline and furazolidone quadruple therapy for H.pylori infection at Sir Run Run Shaw Hospital were identified.All patients received tetracycline,furazolidone,proton pump inhibitor,and bismuth for 14 d as primary or rescue therapy.Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily.RESULTS Three hundred and ninety-four patients[mean age=46.3±13.9,male=137(34.8%),and 309(78.4%)primary therapy]completed tetracycline and furazolidone quadruple therapy for H.pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118(750 mg twice daily)and 119(500 mg three times daily).Eradication rates in the modified tetracycline dose group were 92.40%and in the standard groups,eradication rates were 93.20%for 750 mg twice daily group and 92.43%for 500 mg three times daily group,respectively,without statistical difference(P=0.959).The incidence of adverse events was lower in the modified tetracycline dose(15.3%vs 32.3%and 29.4%;P=0.002)compared to the standard dose group.CONCLUSION In a real-world experience,modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy,comparable to standard tetracycline dose regimens,with a favorable safety profile.

Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.

高效液相色谱-离子阱质谱法测定人血浆中的头孢拉定和青霉素G

目前,β-内酰胺类抗生素在临床抗感染药物中占有十分突出的地位[1],但在近年来的药品不良反应报告中,抗生素类药物引起的不良反应也占据了很高的比例,其中有我国生活环境影响、感染性疾病多的客观因素,但病人用药盲目性大、医生用药随意性多的问题也普遍存在.……

KH_2PO_4和Penicillin对小麦老化种子发芽及幼苗生长的影响

适宜浓度的 KH2 PO4和 Penicillin能明显提高小麦老化种子发芽率、发芽指数、活力指数、幼苗根系活力、叶片叶绿素含量及幼苗长度 ,且能适当降低其种子浸泡液的电导度。其中以 0 .0 2 5 % KH2 PO4+10 0 mg/

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.

Penicillin和Ca^(2+)对玉米老化种子发芽及幼苗生长的影响

用不同浓度的CaCl2和Penicillin及二者复配后对老化的玉米种子进行处理,结果表明,Penicillin 100 mg/L、CaCl20.015 mg/L、二者复配以0.015 mg/L CaCl2+100 mg/L Penicillin能明显提高老化玉米种子发芽率、幼苗根系活力和叶片叶绿素含量,能适当降低其种子浸泡液的电导度,并经方差分析差异达到显著水平。

Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer

AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.

Penicillin和Ca^(2+)对玉米老化种子发芽及幼苗生长的影响

用不同浓度的CaCl2和Penicillin及二者复配后对老化的玉米种子进行处理。结果表明,Peni-cillin100m g/L、CaCl20.015mg/L、二者复配以0.015mg/LCaCl2+100mg/L Penicillin能明显提高老化玉米种子发芽率、幼苗根系活力和叶片叶绿素含量,能适当降低其种子浸泡液的电导度,并经方差分析差异达到显著水平。

Discussion on the dimerization reaction of penicillin antibiotics

Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.

Covalent Assembly of Penicillin Acylase in Mesoporous Silica Based on Macromolecular Crowding Theory

To improve the covalent immobilization of penicillin acylase （PA）, macromolecular crowding theory was applied to its immobilization. Influence of mass ratio of enzyme to the silica, as well as, activation time with glutaraldehyde on the activity of assembled PA, was studied. In the mesopores, the effect of fl-cyclodextrin （β-CD） on the immobilization of the enzyme was also investigated. It was remarkable that the coupled yield and relative activity reached 99.5% and 92.3%, respectively, when penicillin acylase assembled covalently in the mesopores. The results here indicate that mimicked macromolecule crowding could significantly ameliorate the performance of covalently immobilized PA.

Immobilization of penicillin G acylase on paramagnetic polymer microspheres with epoxy groups

Paramagnetic polymer microspheres were synthesized by the inverse suspension polymerizationmethod through polymerization of glycidyl methacrylate,ally glycidyl ether and methacrylamide onthe surface of silica‐coated Fe3O4nanoparticles using N,N’‐methylene‐bis(acrylamide)as across‐linking agent.Penicillin G acylase(PGA)was covalently immobilized on the surface of theparamagnetic microspheres by reacting the amino groups of the PGA molecules with the epoxygroups of the paramagnetic polymer microspheres.The effect of the SiO2coating and the amount ofparamagnetic Fe3O4nanoparticles on the initial activity and the operational stability of the immobilizedPGA was investigated.The results indicated that SiO2played an important role in the polymerization process and paramagnetic polymer microspheres with a SiO2‐coated Fe3O4nanoparticles mass content of7.5%are an optimal support material for PGA immobilization.Immobilized PGA on the paramagnetic polymer microspheres shows a high initial activity of430U/g(wet)and retains99%of its initial activity after recycling10times.Furthermore,immobilized PGA exhibits high thermal stability,pH stability and excellent reusability,which can be rapidly recycled by the aid of magnet.?2018,Dalian Institute of Chemical Physics,Chinese Academy of Sciences.Published by Elsevier B.V.All rights reserved.

Inhibitory effects of jujuboside A on EEG and hippocampal glutamate in hyperactive rat

In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.

Monitoring and Fault Diagnosis for Batch Process Based on Feature Extract in Fisher Subspace

Multivariate statistical process control methods have been widely used in biochemical industries. Batch process is usually monitored by the method of multi-way principal component analysis (MPCA). In this article, a new batch process monitoring and fault diagnosis method based on feature extract in Fisher subspace is proposed.The feature vector and the feature direction are extracted by projecting the high-dimension process data onto the low-dimension Fisher space. The similarity of feature vector between the current and the reference batch is calculated for on-line process monitoring and the contribution plot of weights in feature direction is calculated for fault diagnosis. The approach overcomes the need for estimating or tilling in the unknown portion of the process variables trajectories from the current time to the end of the batch. Simulation results on the benchmark model of penicillin fermentation process can demonstrate that in comparison to the MPCA method, the proposed method is more accurate and efficient for process monitoring and fault diagnosis.

An efficient synthesis of ampicillin on magnetically separable immobilized penicillin G acylase

Penicillin G acylase(PGA) was immobilized on the magnetic hydrophilic polymer microspheres with average pore size of 17.1 nm,specific surface area of 128.2 m2/g and saturate magnetization of 6.4 emu/g.The 96.7%ampicillin yield with 1.60 of the synthesis/hydrolysis(S/H) ratio from 6-aminopenicillanic acid(6-APA) and D-(-)-alpha-phenylglycine methyl ester(D-PGME) can be achieved using the resultant magnetic biocatalyst in ethylene glycol,where only 82.1%yield with 1.40 of the S/H ratio was obtained using the free PGA under the identical reaction conditions.The immobilized PGA can be separated magnetically and recycled for five times without obvious loss of its catalytic activity.

Preparation of 6-APA by Enzymatic Bioconversion in an Emulsion Liquid Membrane Reactor

Production of 6-aminopenicillanic acid (6-APA) by hydrolysis using penicillin acylase (PA) was studied as a model of an enzymatic emulsion liquid membrane (ELM) process. The loss of PA activity was examined for various membrane compositions (organic solvent, surfactant, carrier). The effects of some experimental variables on the stability of emulsion were investigated. It was found that the choice of organic solvent greatly affected the stability of the emulsion. Increasing the concentration of the carrier in the membrane phase increases the transfer rate of substrate and products but also has a destabilizing effect on the emulsion. The recovery of 6-APA obtained by a di-carrier system (N263-N1923) was much higher than those when either of the di-carriers was used separately. The whole process was controlled both by the enzymatic reaction rate and by the transfer rate of the substrate and the products, however, the ratio of them could be changed by varying the composition of the system. For an optimum condition, it was obtained that the recovery ratio of 6-APA was over 80% and the conversion of benzyl penicillin (PG) was up to 90% in the external phase after 30 minutes. Meanwhile, the breakage percentage of the emulsion was less than 2%.

Immobilization of Penicillin G Acylase on Magnetic Nanoparticles Modified by Ionic Liquids

Functionalized ionic liquids containing ethyoxyl groups were synthesized and immobilized on magnetic silica nanoparticles （MSNP） prepared by two steps, i.e., Fe304 synthesis and silica shell growth on the surface. This magnetic nanoparticle supported ionic liquid （MNP-IL） were applied in the immobilization of penicillin G acylase （PGA）. The MSNPs and MNP-ILs were characterized by themeans of Fourier transform infrared spectroscopy （FTIR）, scanning electron microscopy （SEM）, transmission electron microscopy （TEM）, and vibrating sample magnetometer （VSM）. The results showed that the average size of magnetic Fe304 nanoparticles and MSNPs were -10 and -90 nm, respectively. The saturation magnetizations of magnetic Fe304 nanoparticles and MNP-ILs were 63.7 and 26.9 A＇m2·kg^-1, respectively. The MNP-IL was successfully applied in the immobilization of PGA. The maximum amount of loaded enzyme-was about 209 mg·g^-1 （based on carder）, and the highest enzyme activity of immobilized PGA （based on ImPGA） was 261 U·g^-1. Both the amount of loaded enzyme and the activity of ImPGA are at the same leyel of or higher than that in previous reports. After 10 consecutive operat!ons, ImPGA still mainrained 62% of its initial activity, indicating the＇good recovery property of ImPGA activity. The ionic liquid modified magnetic particles integrate the magnetic properties of Fe304 and the structure-tunable properties of ionic liquids, and have extensive potential uses in protein immobilization and magnetic bioseparation. This work may open up a novel strategy to immobilize proteins by ionic liquids.

Poly(GMA/MA/MBAA)Copolymer Beads:a Highly Efficient Support Immobilizing Penicillin G Acylase

The hydrophilic, macroporous and beaded ternary copolymer of glycidyl methacrylate （GMA）/methacrylamide（MA）/N,N＇-methylene-bis（acrylamide）（MBAA）was synthesized using the industrial agents by inverse suspension polymerization. The apparent activity of the immobilized penicillin G acylase reached 1096 IU/g for hydrolysis penicillin G on the beads with diameter of 0.11-0.13 ram, and it changed hardly after 50 cycles. It can be expected to be a good potential in industrial application,

Partition Behavior of Penicillin in Three-liquid-phase Extraction System

Partition behavior of penicillins G and V was studied in a novel three-liquid-phase extraction system,which is composed of butyl acetate (BA),polyethylene glycol (PEG),ammonia sulfate (NH4)2SO4 and water (H2O). The main components in the top,middle and bottom phases are butyl acetate,polyethylene glycol aqueous solution and ammonia sulfate aqueous solution,respectively. Some parameters such as partition coefficients Di/j and mass fractions Ei of penicillins G and V were determined at the room temperature,respectively. Experimental efforts have been made to investigate the partition behavior of penicillin in the three-liquid-phase extraction system,including initial concentrations of phase-forming components PEG and (NH4)2SO4,PEG molecular weight,pH,initial concentration of penicillin. The results indicated that penicillins G and V have the similar partition behavior. They preferentially distribute into the middle phase with the increase of initial concentration of phase-forming components and into the top phase with the decrease of pH,while partition coefficient Dm/b is hardly affected by pH value. The variation of PEG molecular weight has little effect on mass fractions of penicillin. The increase of initial concentration of penicillins G and V could lead to the increase of Dt/b,Dm/b and the decrease of Dt/m,while their mass fractions in all phases were almost independent on their initial concentrations.