In vitro and in vivo studies on the role of dimethylsulfoxide (DMSO) in resensibilization of bacterial strains resistant to antibiotics and chemotherapeutic agents

Resensibilization in vitro to seven antibiotics under the influence of DMSO was studied in 624 resistant strains of five species of bacteria (E. coli, S. typhi, S. pyogenes, S. viridans, S. aureus), 61 strains of tubercle bacilli resistant to isonicotinic acid hydrazide (INH) and 19 strains of tubercle bacilli resistant to rifampicin (RMP). DMSO in concentrations of 0.1-10.0% caused reversion of sensitivity in strains of E. coli, S. pyogenes and S. viridans. Reversion in vivo of sensitivity to INH of tubercle bacilli was studied in experimental tuberculosis of guinea pigs. Tubercle bacilli previously resistant to INH recovered complete sensitivity to the drug, enabling animals infected with the INH-resistant strain of bacilli to be treated with INH.     

Microbial inhibitory properties and stability of topotecan hydrochloride injection

The viability of five microorganisms in topotecan 1 mg/mL (as the hydrochloride salt) in sterile water and the stability of the drug were studied. Duplicate portions of topotecan 1 mg/mL were inoculated with Escherichia coli. The process was repeated for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Samples were removed from each solution initially and after 6, 16, and 24 hours and 3, 7, 14, 21, and 28 days of incubation at 20-25 degrees C. To test stability, vials of reconstituted topotecan hydrochloride injection were stored at each of three temperatures--5, 25, and 30 degrees C--and other vials were used for time zero analysis. For each temperature, vials were removed at 1, 7, and 14 days and the remaining vials at 28 days for analysis by high-performance liquid chromatography and for visual and pH assessment. P. aeruginosa, S. aureus, and E. coli lost viability at 16 hours, 24 hours, and 28 days, respectively. C. albicans and A. niger did not lose viability, but their numbers did not grow. No differences in color or clarity were observed, and pH was constant. In all solutions, the topotecan concentration was > 98% of the initial concentration. Topotecan 1 mg/mL in sterile water stored at 20-25 degrees C for up t 28 days did not support growth of the five microorganisms studied; in solutions stored at 5, 25, or 30 degrees C for up to 28 days, topotecan 1 mg/mL remained stable.     

含锰反萃液制备高纯碳酸锰工艺研究

以含锰反萃液为原料,经针铁矿法除铁、硫化除重金属、碳化、洗涤制备了合格高纯碳酸锰。考察了终点pH、反应温度对除铁率的影响和(NH4)2S加入量、温度、反应时间对重金属去除率的影响,结果表明:在pH=4.0、反应温度95℃的条件下可将铁除至1.5 mg/L以下;除铁滤液加入2.2倍计量比的(NH4)2S,在反应温度35℃、反应时间60 min的条件下,Ni、Co、Zn可降低至1 mg/L以下;除重金属滤液加入碳酸氢铵调节pH在7.0~7.2,过滤、洗涤,获得满足HG/T 2836—2011(Ⅰ型)产品标准的合格高纯碳酸锰,锰回收率为93.9%。     

Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of experimental endocarditis due to methicillin-susceptible or -resistant Staphylococcus aureus

Levofloxacin is the L isomer of ofloxacin, a racemic mixture in which the L stereochemical form carries the antimicrobial activity. Levofloxacin is more active than former quinolones against gram-positive bacteria, making it potentially useful against such pathogens. In this study, levofloxacin was compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of experimental endocarditis due to two methicillin-susceptible Staphylococcus aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates. The four test organisms were susceptible to ciprofloxacin, the levofloxacin MICs for the organisms were low (0.12 to 0.25 mg/liter), and the organisms were killed in vitro by drug concentrations simulating both the peak and trough levels achieved in human serum (5 and 0.5 mg/liter, respectively) during levofloxacin therapy. Rats with aortic endocarditis were treated for 3 days. Antibiotics were injected with a programmable pump to simulate the kinetics of either levofloxacin (350 mg orally once a day), ciprofloxacin (750 mg orally twice a day), flucloxacillin (2 g intravenously four times a day), or vancomycin (1 g intravenously twice a day). Levofloxacin tended to be superior to ciprofloxacin in therapeutic experiments (P = 0.08). More importantly, levofloxacin did not select for resistance in the animals, in contrast to ciprofloxacin. The lower propensity of levofloxacin than ciprofloxacin to select for quinolone resistance was also clearly demonstrated in vitro. Finally, the effectiveness of this simulation of oral levofloxacin therapy was at least equivalent to that of standard treatment for MSSA or MRSA endocarditis with either flucloxacillin or vancomycin. This is noteworthy, because oral antibiotics are not expected to succeed in the treatment of severe staphylococcal infections. These good results obtained with animals suggest that levofloxacin might deserve consideration for further study in the treatment of infections due to ciprofloxacin-susceptible staphylococci in humans.     

Self-reported satisfaction with life and physical health in long-term cancer survivors and a matched control group

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.     

5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.     

某砂岩铀矿床矿石中性浸出性能试验

对某砂岩型铀矿石开展不同O2剂量的中性浸出试验。结果表明,试验矿石中性浸出性能较差,铀浓度基本低于20mg/L,在25.2的高液固比条件下,铀浸出率仅为35.36%~41.85%;前期以六价铀浸出为主,浸出强度与HCO3^-浓度正相关;六价铀基本被浸出后,有O2、无O2的浸出差别明显,但O2剂量在30~200mg/L变化时浸出差别并不显著;相对高的pH有利于形成更稳定的铀酰络合物和降低铀的氧化还原临界电位,但应避免高pH引起碳酸钙沉淀。在地浸生产保持不低于800mg/L的HCO3^-和维持浸出液10~20mg/L的余氧是合适的。     

制备方法对新型纳米TiO2抑菌片抑菌活性的影响

制备了4种TiO₂抑菌片，用于大肠杆菌和金黄色葡萄球菌的抑菌实验评价。运用BET、XRD、IR和SEM等进行表征，并对最小抑菌浓度和最低灭菌浓度进行测定。实验结果表明:不同方法制备的纳米TiO₂抑菌片体现出不同的抑菌活性，水热合成法制备的样品2的抑菌活性最高，抑菌圈直径保持在20 mm可持续稳定24 h，对大肠杆菌的最小抑菌浓度和最低灭菌浓度分别约为50 mg/L和70 mg/L，对金黄色葡萄球菌的最小抑菌浓度和最低灭菌浓度分别约为50 mg/L和70 mg/L。同时发现，样品的抑菌活性与内部晶型的差异、表面官能团的种类及数量及微观形貌有关。本研究可为高效TiO₂抑菌片的制备提供参考。      

沸石改性及其在硫酸锌溶液中的脱氟性能

采用硝酸镧溶液浸泡负载元素镧的方法对天然沸石进行改性,通过静态吸附法研究改性沸石脱除硫酸锌模拟溶液的脱氟性能,考察改性沸石用量、pH值、吸附时间、吸附温度4个因素对改性沸石除氟性能的影响;并利用EDX、BET等分析手段对沸石改性前后的成分、形貌及微观结构进行表征.结果表明：当改性沸石用量为7.5 g/L,吸附时间25 min,反应温度为40℃,pH=4时改性膨润土的除氟量最大,氟离子浓度由100 mg/L降至45.56 mg/L,符合工业生产中所规定的小于50 mg/L;多种分析手段表明,改性后镧元素有效负载在沸石表面,同时沸石的层间距和比表面积都有所增加,有利于提高沸石的除氟性能.     

氨—碳铵法浸出含锌烟灰

研究氨—碳铵体系中pH、总氨浓度、液固比(L/S)、反应温度、反应时间等因素对三种含锌烟灰中锌和主要杂质元素浸出行为的影响。结果表明,较佳的工艺条件是:浸出剂总氨浓度9mol/L、pH=10.00、L/S=5、反应温度50℃、反应时间60min。此时锌浸出率大于80%。     

偏重亚硫酸钠—空气法处理氰化尾渣

采用偏重亚硫酸钠—空气法处理氰化尾渣进行脱氰的研究,考察Na2S2O5浓度、Cu2+浓度、空气速率、初始pH和反应时间对脱氰效果的影响。结果表明,在Na2S2O5浓度0.2g/L、Cu2+浓度80mg/L、空气鼓入速率250mL/min、初始pH≈10的条件下反应2h,氰化尾渣矿浆中全氰浓度从91.5mg/L降到0.2mg/L左右,可以满足GB8978-1996污水综合排放标准。     

Protein binding effects of salivary excretion of phenobarbital in dogs

The salivary excretion of phenobarbital was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately after intravenous administration in beagle dogs. (1) The alterations in the proportions of saliva secreted by the different glands were produced by salivation stimulants such as citric acid, ascorbic acid, sodium chloride and sodium glutamate. (2) The phenobarbital concentrations in both Pr amd MS were lower than those in plasma. The drug concentrations in MS were significantly lower than in Pr with stimulus of 10% citric acid of 15% sodium chloride (p less than 0.05). There was a significant correlation between phenobarbital concentration in each saliva and plasma specimen ( p less than 0.05). (3) The stimulation with 10% citric acid produced higher saliva /plasma drug concentration ratios (S/P ratios: 0.923 +/- 0.175 for Pr, 0.633 +/- 0.073 for MS) than that with 15% sodium chloride (S/P ratios: 0.597 +/- 0.071 for Pr, 0.509 +/- 0.067 or MS). (4) The S/P ratios were hardly influenced by salivary flow rates, at least under the experimental conditions examined in this study. (5) The increased S/P ratios were observed with higher salivary pH and then the equation of Matin et al. 3) seemed to hold for the average values of salivary pH and S/P ratio. (6) The stimulation with 10% citric acid produced higher protein concentration in saliva and higher S/P ratio than that with 15% sodium chloride following alternate stimulations in the same dog.     

均苯四甲酸二酐改性甘蔗渣及其对冶金废水中铅的吸附性能研究

以经碱和醇预处理过的甘蔗渣为原料,采用戊二醛为交联剂,均苯四甲酸二酐(PMDA)为改性剂,对甘蔗渣纤维进行羧基化改性,并用于冶金废水中铅的吸附。结果表明,甘蔗渣改性最佳工艺条件为:戊二醛浓度1%、PMDA添加量5%、液固比8∶1、改性温度60℃。红外光谱分析表明甘蔗渣中引入了苯环和羧基基团,戊二醛和PMDA成功改性甘蔗渣。SEM发现改性后的甘蔗渣形成了交联状,表面积增大。最佳吸附条件:吸附时间2.0h、吸附温度20℃、溶液pH=4,溶液中Pb的初始浓度70mg/L,Pb吸附率可达到98.8%。     

Green fluorescent protein as a noninvasive intracellular pH indicator

It was found that the absorbance and fluorescence of green fluorescent protein (GFP) mutants are strongly pH dependent in aqueous solutions and intracellular compartments in living cells. pH titrations of purified recombinant GFP mutants indicated >10-fold reversible changes in absorbance and fluorescence with pKa values of 6.0 (GFP-F64L/S65T), 5.9 (S65T), 6.1 (Y66H), and 4.8 (T203I) with apparent Hill coefficients of 0.7 for Y66H and approximately 1 for the other proteins. For GFP-S65T in aqueous solution in the pH range 5-8, the fluorescence spectral shape, lifetime (2.8 ns), and circular dichroic spectra were pH independent, and fluorescence responded reversibly to a pH change in <1 ms. At lower pH, the fluorescence response was slowed and not completely reversed. These findings suggest that GFP pH sensitivity involves simple protonation events at a pH of >5, but both protonation and conformational changes at lower pH. To evaluate GFP as an intracellular pH indicator, CHO and LLC-PK1 cells were transfected with cDNAs that targeted GFP-F64L/S65T to cytoplasm, mitochondria, Golgi, and endoplasmic reticulum. Calibration procedures were developed to determine the pH dependence of intracellular GFP fluorescence utilizing ionophore combinations (nigericin and CCCP) or digitonin. The pH sensitivity of GFP-F64L/S65T in cytoplasm and organelles was similar to that of purified GFP-F64L/S65T in saline. NH4Cl pulse experiments indicated that intracellular GFP fluorescence responds very rapidly to a pH change. Applications of intracellular GFP were demonstrated, including cytoplasmic and organellar pH measurement, pH regulation, and response of mitochondrial pH to protonophores. The results establish the application of GFP as a targetable, noninvasive indicator of intracellular pH.     

HEDP和渗透剂T协同阻垢性能的研究

静态阻垢法研究了1-羟基乙叉-1，1-二膦酸(HEDP)的阻垢性能，考查了几个主要因素对HEDP阻垢性能的影响。结果表明HEDP的加入量为12．0mg／L．渗透剂T的浓度为0．6mg／L时阻垢率最大，为75．6％；渗透剂T的加入明显地改善了HEDP的阻垢性能．阻垢性能随Ca^2 浓度的增加而增加，在pH值为6到9时药剂的阻垢性能稳定。     

Pharmacokinetic and clinical evaluation of cefozopran in premature and newborn patients

Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of approved indications in infectious diseases for adult patients, was administered to premature and newborn patients to evaluate the pharmacokinetics and the clinical efficacy. 1. Pharmacokinetics CZOP was intravenously administered at doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients, and the blood concentrations and urinary excretion rate were examined. The blood CZOP concentrations were 31.7 and 65.5 micrograms/ml at 30 minutes after administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7% within 6 hours after administration, respectively. In the patient given 21.4 mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after administration and the elimination half life was 3.97 hours. The urinary recovery was 29.6% within 5 hours after administration. 2. Clinical results The clinical efficacy was evaluated in 19 patients and judged "good" or better in 13 of them with the efficacy rate or 68.4%. The bacteriological response was evaluated in 10 patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1 strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2 strains) and E. coli (2 strains) were isolated as possible causative organisms. With exception of 1 strain each of S aureus and H influenzae, which were not tested after the treatment with CZOP, all of these strains were found to be eradicated. 3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal alterations of laboratory test values. Safety evaluation was made in 24 patients. ADRs of signs and symptoms were recognized in none of them. As abnormal alterations of laboratory test values, increased eosinophils in 3 patients, elevated GOT in one and elevated GPT in one were recognized. These results indicate that CZOP is a drug useful for treatment of infections in premature and newborn patients.     

复合铵盐浸出风化壳淋积型稀土矿的研究

采用复合铵盐作浸出剂浸出风化壳淋积型稀土矿中的稀土。考察浸出剂的配比、浓度、液固比、流速、pH等因素对稀土浸出率的影响。结果表明,NH4Cl、NH4NO3、(NH4)2SO4质量比为4∶5∶6的复合铵盐浸出剂为最佳组合;液固比越大、流速越慢,浸出率越高;当浸出剂浓度为10g/L、pH=3.5时浸出效果最好。     

稀土负载生物炭的制备及其对低浓度氨氮的吸附特性

对微波/稀土元素铈吸附剂的制备条件及其吸附降解低浓度氨氮的反应条件进行优化,并采用XRD、SEM和FTIR对负载型吸附剂进行了表征。实验结果表明,负载型吸附剂内部结构发生变化,比表面积增大,羟基数量增多;负载后的生物炭对氨氮的处理效果明显优于原生物炭,其较为合适的制备条件为固液比(指原生物炭质量与氯化亚铈溶液体积之比,单位g/mL)1:25,浸渍pH 10;在氨氮溶液浓度为50 mg/L,初始pH为10,反应温度为50℃,反应时间为120 min,吸附剂投加量为5 g/L条件下,氨氮吸附量达到最大,为11.297 mg/g,且反应过程符合准二级动力学模型。      

高铁酸盐对焦化废水中COD、NH_3-N的处理效果的研究

高铁酸盐加入量对COD和NH3-N去除效果的实验结果表明:在常温下,当高铁酸盐的加入量为14mg/L时,焦化废水中COD的质量浓度由320mg/L下降到88mg/L,去除率达72.5%;NH3-N质量浓度由68mg/L下降到14.9mg/L,去除率达78.1%。     

Interactions between HMR 3647, a new ketolide, and human polymorphonuclear neutrophils

HMR 3647, a new ketolide, is active upon intracellular pathogens. We previously demonstrated that HMR 3004 (RU 64004), another ketolide, is highly concentrated by human polymorphonuclear neutrophils (PMNs). This prompted us to evaluate whether the presence of a 3-keto group instead of an L-cladinose, a neutral sugar characteristic of erythromycin A derivatives, confers peculiar pharmacokinetic properties with regard to cellular accumulation and efflux. After incubation with the radiolabelled drug, HMR 3647 uptake was determined by a velocity gradient centrifugation technique. HMR 3647 was avidly concentrated by PMNs, without saturation, over a 3-h incubation period, with cellular-to-extracellular concentration ratios of 31 +/- 4.2 at 5 min and up to 348 +/- 27.1 at 180 min. About 60% of HMR 3647 was located in the granular compartment; less than 6% was associated with the membranes. HMR 3647 gradually egressed from loaded cells placed in drug-free medium. Uptake was dependent on environmental temperature (activation energy, 128 +/- 9. 4 kJ/mol) but not on extracellular pH. HMR 3647 displayed Michaelis-Menten saturation kinetics with a mean Vmax of 2315 ng/2.5 x 10(6) PMNs/5 min and a mean Km of 117 mg/liter (144 microM). As already observed with erythromycin A-derived macrolides, extracellular Ca2+ was necessary for optimal uptake of HMR 3647. Interestingly, verapamil increased the uptake of HMR 3647 at 5 min, but this was followed by gradual inhibition at later incubation times, a phenomenon probably related to stimulation of drug efflux. The impact of intracellular accumulation of HMR 3647 on PMN functions was also investigated. In contrast to other erythromycin A derivatives, HMR 3647 only weakly triggered granule exocytosis, but it inhibited superoxide anion production in a time- and concentration-dependent manner, with concentrations which inhibited 50% of control response of 55 (67 microM) (5 min) and 30 (36 microM) (30 min) mg/liter for formyl-methionyl-leucyl-phenylalanine stimulation and 117 (143 microM) (5 min) and 44 (54 microM) (30 min) mg/liter for phorbol myristate acetate stimulation.