Targeted eco-pharmacovigilance as an optimized management strategy for adverse effects of pharmaceuticals in the environment

From a perspective of drug administration, eco-pharmacovigilance (EPV) has been proposed as a new approach to prevent the environmental risks posed by pharmaceutical emerging contaminants. However, it is impracticable to practice unitary and rigor EPV process for all the pharmaceutical substances with complex and diversified chemical, biological or toxicological properties. We proposed the “targeted EPV” that is the science and activities associated with the targeted detection, evaluation, understanding, and prevention of adverse effects of high-priority hazardous pharmaceuticals in the environment, especially focusing on the control of main anthropogenic sources of pharmaceutical emission among key stakeholders in high-risk areas could be used as an optimized management strategy for pharmaceutical pollution. “Targeted EPV” implementation should focus on the targeted monitoring of the occurrence of high-priority pharmaceuticals in environmental samples, the targeted reporting of over-standard discharge, the targeted management for main emission sources, the targeted legislation and researches on high-priority pharmaceutical pollutants, as well as the targeted educational strategies for specific key populations.     

Chlorinated pesticide residues in human breast milk collected from southern Jordan in 2012/2013

Chlorinated pesticide residues in human breast milk from five southern Jordan districts were analyzed in 2012/2013. The total number of samples from all districts was 100. The number of samples gathered from each district was collected according to their population densities. The present study shows that 59% of the samples which contained pesticides’ residues were p,p’-DDE, 30% contained β-HCH, 10% contained p,p′-DDT, 6% contained α-HCH, 2% contained heptachlor and 1% contained endrin. These human milk samples were free of aldrin, dieldrin, α-endosulfan, β-endosulfan, HCB, γ-HCH, o,p′-DDD, o,p′-DDT and o,p′-DDE. The levels of the six mentioned compounds detected in all mother’s milk samples were higher in Ghor El-Safi district compared with the other four districts. In this study, it is recommended to continue the pesticides residues monitoring in all parts of Jordan, particularly in Ghor El-Safi district and other regions in the cultivated Jordan Valley.     

HPLC analysis of some allowable-antibiotic multiresidues in farmed rainbow trout in Iran

This study aimed to investigate the occurrence of antibiotic residues in rainbow trout muscle samples (n?=?74) obtained from Iranian trout farms. The levels of the antibiotics were determined by in-house validated HPLC methods. Oxytetracycline, tetracycline, enrofloxacin, ciprofloxacin, and florfenicol residues were detected in 6.76%, 37.8%, 31.1%, 10.8%, and 14.9% of the samples, respectively; while chlortetracycline was not detected. The detected range of concentrations for positive samples was 8.94–81.2 μg/kg for oxytetracycline, 7.99–98.4 μg/kg for tetracycline, 6.75–87.4 μg/kg for enrofloxacin, 5.83–11.5 μg/kg for ciprofloxacin, and 49.9–313.6 μg/kg for florfenicol. None of the samples exceeded the maximum residue levels (MRLs) established by the Institute of Standards and Industrial Research of Iran. The co-occurrence of antibiotics was detected in 40.5% of the analyzed samples. The frequency of co-occurrence of enrofloxacin-tetracycline was the highest (16.2%). Despite the fact that concentrations of the analyzed antibiotics in trout samples did not exceed the MRLs, their co-occurrence in such a level could be a serious public health problem.     

Insecticide Residues in Soil,Water, and Eggplant Fruits and Farmers’ Health Effects Due to Exposure to Pesticides

Objectives

Eggplant (Solanum melongena L.) is an important vegetable crop that is widely cultivated in the tropical and subtropical areas in Asia. Globally, the top three eggplant producers are China, India, and Egypt. The Philippines has been one of the top 10 eggplant-producing countries based on area planted and crop productivity. This study aims to describe the insecticide residues found in soil, water, and eggplant fruits in eggplant farms in Sta. Maria, Pangasinan.

Methods

The study design is a cross sectional of randomly selected eggplant farms in Sta. Maria, Pangasinan. Soil, water, and eggplant fruits were collected and subjected to gas chromatography (Shimadzu) analysis for multi-pesticide residues.

Results

Farmers from Sta. Maria, Pangasinan were found to be applying a broad spectrum of insecticides on their eggplant crop. Soil samples from 11 (about 42 %) out of the 26 farms tested positive for insecticide residues, six of which from four farms exceeded the acceptable maximum residue limit. These residues were profenofos, triazophos, chlorpyrifos, cypermethrin, and malathion. No insecticide residues were detected from water samples taken from the 26 farms. Cypermethrin and chlorpyrifos were the insecticide residues detected in eggplant fruit samples. A maximum of 20 % of the eggplant samples tested positive for insecticide residues. In the eggplant fruit study, all farmers have been using Prevathon^® for 24 years at a rate of 10 ml/application, and Malathion^® for 25 years at about 16.5 ml/application, respectively equivalent to 0.24 liter-years and 0.413 liter-years of exposure. Similarly, to the findings in the soil and water study, although Brodan^® and Magnum^® were not prevalently applied, the farmers’ liter-years of exposure to these insecticides, and their active ingredients, were highest at about 18.92 and 10.0, respectively. The farmers and farm workers in the soil and water study reported experiencing itchiness of the skin (63.8 %), redness of the eyes (29.3 %), muscle pains (27.6 %), and headaches (27.6 %), as being related to their pesticide exposure.

Conclusion

In summary, a maximum of 20 % of the eggplant samples tested positive for insecticide residues at any one stage of sampling done. The farmers and farm workers also reported of pesticide-related illnesses but none of them sought any medical attention. Intervention to reduce the farmers’ pesticide exposure can focus on the risk factors identified, primarily the toxicity of pesticides used, the unsafe application practices, and the adverse health effects of pesticide exposure.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-014-0425-3) contains supplementary material, which is available to authorized users.     

中药外源性污染物检测技术的现代研究

中药外源性污染物残留现已成为引起中药不良反应的重要原因之一,按照其来源不同主要包括农/兽药残留、重金属污染、真菌毒素残留、病原微生物污染及其他有机污染物残留。对中药的主要外源性污染物的检查对象及检测方法的现代研究进行综述,为补充、完善、提升中药质量安全体系提供参考和依据。     

Predicting Enzyme Functional Surfaces and Locating Key Residues Automatically from Structures

Locating functionally important protein surfaces and identifying the catalytic site residues are critical for studying enzyme functions. Here, we present a method for predicting and characterizing catalytic sites of enzymes that is fold-independent. By extract atomic patterns of catalytic residues in surface pockets computed geometrically, we develop a library of atomic patterns on protein functional surfaces of ca 700 structures. Together with propensities of secondary structures and residue occurrence in active sites, we develop a method to identify functionally important surfaces on protein structures and to locate key residues. We discuss application of our methods to amylase, dioxygenase, deaminase, dehalogenase, and hydratase. A large scale cross-validated prediction study shows that our method is sensitive and specific. Our method can used to study enzyme function, drug design, and engineering novel biochemical function.     

Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH

The ubiquitous AE2/SLC4A2 anion exchanger is acutely and independently regulated by intracellular (pH_i) and extracellular pH (pH_o), whereas the closely related AE1/SLC4A1 of the red cell and renal intercalated cell is relatively pH-insensitive. We have investigated the contribution of nonconserved charged residues within the C-terminal transmembrane domain (TMD) of AE2 to regulation by pH through mutation to the corresponding AE1 residues. AE2-mediated Cl⁻/Cl⁻ exchange was measured as 4,4′-di-isothiocyanatostilbene-2,2′-disulfonic acid-sensitive ³⁶Cl⁻ efflux from Xenopus oocytes by varying pH_i at constant pH_o, and by varying pH_o at near-constant pH_i. All mutations of nonconserved charged residues of the AE2 TMD yielded functional protein, but mutations of some conserved charged residues (R789E, R1056A, R1134C) reduced or abolished function. Individual mutation of AE2 TMD residues R921, F922, P1077, and R1107 exhibited reduced pH_i sensitivity compared to wt AE2, whereas TMD mutants K1153R, R1155K, R1202L displayed enhanced sensitivity to acidic pH_i. In addition, pH_o sensitivity was significantly acid- shifted when nonconserved AE2 TMD residues E981, K982, and D1075 were individually converted to the corresponding AE1 residues. These results demonstrate that multiple conserved charged residues are important for basal transport function of AE2 and that certain nonconserved charged residues of the AE2 TMD are essential for wild-type regulation of anion exchange by pH_i and pH_o. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. A. K. Stewart and C. E. Kurschat have contributed equally to this work.     

High throughput ranking of recombinant avian scFv antibody fragments from crude lysates using the Biacore A100

Advances in molecular evolution strategies have made it possible to identify antibodies with exquisite specificities and also to fine-tune their biophysical properties for practically any specified application. Depending on the desired function, antibody/antigen interactions can be long-lived or short-lived and, therefore, particular attention is needed when seeking to identify antibodies with specific reaction-rate and affinity properties. Surface plasmon resonance (SPR) biosensors routinely generate sensitive and reliable kinetic data from antibody/antigen interactions for both therapeutic and diagnostic applications. However, many kinetic-based screening assays require rigorous sample preparation and purification prior to analysis. To ameliorate this problem, we developed a rapid and reliable assay for characterising recombinant scFv antibody fragments, directly from crude bacterial lysates. Ninety-six scFv antibodies derived from chickens immunised with C-reactive protein (CRP) were selected by phage display and evaluated using the Biacore A100 protein interaction array system. Antibodies were captured from crude bacterial extracts on the sensor chip surface and ranked based on the percentage of the complex left (% left) after dissociation in buffer. Kinetic rate constants (k(a) and k(d)) and affinity (K(D)) data were obtained for six clones that bound monomeric CRP across a broad affinity range (2.54 x 10(-8) to 3.53 x 10(-10) M). Using this assay format the A100 biosensor yielded high quality kinetic data, permitting the screening of nearly 400 antibody clones per day.     

一种大豆秸秆蜜环菌培养基及其生产条件的优化

目的 为了解决天麻栽培中对木材的大量使用造成的森林资源破坏及栽培成本增加问题,该研究对农作物余料替代木材（或木屑）培养蜜环菌的可行性进行了探讨,以期降低天麻的栽培成本,同时使农作物余料得到有效利用,进而保护林木资源。方法 观察蜜环菌的生长情况,划线法测量蜜环菌生长速度;苯酚浓硫酸法测定不同培养基中蜜环菌的总多糖含量;为了进一步优化大豆秸秆培养基配比,对主料配比、蔗糖含量、无机盐含量及含水量进行四因素三水平L₉（3⁴）正交优化试验。结果 通过比较不同培养基培养中蜜环菌的生长情况,发现大豆秸秆培养基培养的蜜环菌从接种第4天就开始生长,菌丝长势好,生长速度为0.352 cm·d^-1,是桦木屑培养基生长速度0.283 cm·d^-1的1.48倍;大豆秸秆培养基培养的蜜环菌总多糖含量最高,为39.260 mg·g^-1,远远高于桦木屑培养的蜜环菌总多糖含量17.028 mg·g^-1,大豆秸秆培养基优势明显;主料（大豆秸秆与麦麸）配比为8∶2,蔗糖含量为主料的1%,无机盐含量为主料含量的0.5%,含水量50%时,蜜环菌生长速度稳定为0.392 cm·d^-1。结论 该研究结果为天麻栽培中使用大豆秸秆培养基替代木材（或木屑）培养基培养的蜜环菌提供了依据,为天麻在栽培中减少林木资源浪费、保护自然环境提供了参考。     

10种中药材及饮片亚硫酸盐残留检测结果分析

目的 对市场上抽取的10种中药材及其饮片进行二氧化硫残留量测定,并对结果进行统计分析,提出标准建议和监管建议.方法 采用《中国药典》2010年版第一增补本中二氧化硫残留量测定法,按照《中国药典》2010年版第二增补本中的限量要求对检测结果进行统计分析.结果与结论 共检测10个品种896批中药材及饮片,开展过中药饮片无硫化专项整治工作地区的样品结果满意.建议应加强对二氧化硫残留量限度标准的实施,严格市场监管,加大政策扶持力度,指导规范加工方法的转化,进而保证中药饮片质量安全.