Life cycle of the damselfly Calopteryx atrata in relation to pesticide contamination

The life cycle of the damselfly Calopteryx atrata was investigated in relation to pesticide contamination occurring in its aquatic habitat. Calopteryx atrata emerged from the River Onogawa around May and stayed as immature adults in forests away from the stream. From late June to mid-August, mature adults were engaged in reproduction at the stream. On the other hand, pesticide contamination occurred from April to August with its peak in May and June, following transplantation of young rice plants. Mature nymphs of C. atrata experienced pesticide contamination, but may have tolerated it. Hatched nymphs had high susceptibility to two of the commonly used insecticides, fenitrothion (mortality occurred at >4.0 g l^-1 in 24 h and at >2.0 g l^-1 in 48 h) and fenthion (>2.0 g l^-1 in 24 h and >1.0 g l^-1 in 48 h). Hatching was estimated to occur mainly in August, when pesticide contamination was not as high as the susceptibility level. However, the level of pesticide contamination in August is variable due to its origin from aerial spraying, so hatched nymphs may experience a hazardous amount of pesticides depending on the year or place. The population of C. atrata does not escape the risk of pesticide contamination completely and may be affected by it.     

Anti-staphylococcal activity of ent-kaurane-type diterpenoids from Croton tonkinensis

Ent-kaurane-type diterpenpoids 1–11, isolated from the dried leaves of the endemic Vietnamese medicinal plant Croton tonkinensis Gagnep. (Euphorbiaceae), were evaluated for inhibitory activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) strains. The most active diterpenoids, 2, 3, and 8, exhibited minimum inhibitory concentrations (MICs) of 32, 500, and 125 g/ml, respectively, against MRSA strains.     

Constituents of Laurus nobilis L. inhibit recombinant human lanosterol synthase

Extracts from 37 kinds of foods and foodstuffs were tested for inhibitory activity against recombinant human lanosterol synthase. Among them, extracts from five samples showed significant inhibition. Potent activity (55%) was found in 95% ethanol extract of Laurus nobilis L. Therefore, large-scale methanol extraction of the plant was carried out, and the constituents were separated by partition and fractionation by silica gel chromatography and HPLC. Four flavonoids, kaemperol 3-O-[2,4-O-di-E-p-coumaroyl--l-pyranorhamnoside] (1); 3,3,4,5,6,7,8-heptamethoxyflavone (2); 3,4,5,6,7,8-hexamethoxyflavone (nobiletin) (3); and 4,5,6,7,8-pentamethoxyflavone (tangeretin) (4); and six sesquiterpens, eremanthine (5), dehydrocostus lactone (6), costunolide (7), zaluzanin C (8), zaluzanin D (9) and reynosin (10) were isolated. Eremanthine (5) showed the most potent activity, 70% inhibition, at the concentration of 500 M.     

Sesquiterpenoids from Ferula fukanensis and their inhibitory effects on nitric oxide production

Six sesquiterpene derivatives, 2,3-dihydro-7-methoxy-2S*, 3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (1) and 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (2), nerolidol (3), 1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-ninyl-6(E),10-dodecadien-1-one (4), 1-(2,4-dihydroxyphenyl)-3,7-dimethyl-3-vinyl-8-(4-methyl-2-furyl)-6(E)-octen-1-one (5) and dshamirone (6) were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The sesquiterpenoids inhibited nitric oxide (NO) production and inducible NO synthase gene expression by a murine macrophage-like cell line (RAW 264.7) [1], which was activated by lipopolysaccharide and recombinant mouse interferon-.     

Insecticides and Arable Weeds: Effects on Germination and Seedling Growth

The decline of many arable weed species in Northern Europe has been attributed to the intensification of modern agriculture and in particular, increasing pesticide use. In this study, we examined the effect of two insecticides, dimethoate and deltamethrin, on the germination and seedling growth of six arable weed species. Although germination was unaffected by insecticide application, seedling growth of four species was decreased by exposure to deltamethrin (Capsella bursa-pastoris and Poa annua), dimethoate (Agrostemma githago), or by both insecticides together (Urtica urens). While increased herbicide use, seed cleaning, and changing sowing times may be of primary importance in explaining the reduction of northern Europe’s arable weed flora, our results indicate that insecticide use may also be a contributory factor. Moreover, those species that exhibit apparent tolerance of the insecticides tested, particularly the grass Avena fatua, may benefit from continued insecticide use. The ability to tolerate these agrochemicals, in tandem with reduced herbivory and competition from plants, whose growth is reduced by insecticide application, is likely to confer a significant competitive advantage on insecticide-resistant weed species.     

Thyroid Function in Nestling Tree Swallows and Eastern Bluebirds Exposed to Non-Persistent Pesticides and <Emphasis Type="BoldItalic">p</Emphasis>, <Emphasis Type="BoldItalic">p</Emphasis>′-DDE in Apple Orchards of Southern Ontario,Canada

This study examined the associated effects of pesticides and persistent residues of p,p-DDE on thyroid function in 16-day-old tree swallows (Tachycineta bicolor) and 12-day-old eastern bluebirds (Sialia sialis). Apple orchards sprayed with pesticides in current use and reference sites were chosen for study in southern Ontario, Canada, during 2000–2001. We assessed thyroid hormone concentrations (plasma and muscle thyroxine [T₄], and triiodothyronine [T₃]) and the response to a challenge with thyroid stimulating hormone (TSH) as well as parameters of thyroid histology. Individual nests were exposed to as many as seven individual pesticide applications and up to five pesticide mixtures. Concentrations of p,p-DDE in eggs from both species were highest in orchard sites, and ranged from 0.05 to 5.44 mg/kg wet weight for tree swallows, and from 0.17 to 95.4 mg/kg for eastern bluebirds. In 2000, tree swallows from sprayed orchards had elevated plasma T₄ concentrations, and thyroid glands with collapsed follicles, hypertrophic epithelia, and higher follicular epithelial cells relative to chicks from reference sites. Plasma T₄ concentration was positively correlated with the total number of pesticide mixtures applied during egg incubation through chick rearing. In 2001, basal plasma T₃ concentration in tree swallow chicks did not differ between orchard and reference sites, though there were differences among orchards; T₃ was positively correlated with total number of individual sprays applied during egg incubation through chick rearing. Tree swallows challenged with TSH showed no significant difference in thyroid hormone concentration or follicular epithelial cell height between exposure groups; however, a significantly greater proportion of chicks from reference sites were found to have thyroids with focal or diffuse hypertrophic epithelia relative to orchard chicks. In 2001, bluebirds from sprayed orchards had significantly higher T₃ concentrations in response to TSH challenge; this response was positively correlated with the total number of pesticides applied during egg incubation through chick rearing.     

A repeated tests procedure to assess onset and duration of the cue properties of (−)Δ 9-THC, (−)Δ 8-THC-DMH and (+)Δ 8-THC

Rats were trained in a two-lever operant box in a drug discrimination procedure to respond differentially to the effects induced by 3 mg/kg of (-) ⁹-tetrahydrocannabinol and the drug vehicle. Tests with (-) ⁸-THC and the dimethyl-heptyl (DMH) homologue of (-) ⁸-THC indicated that (-) ⁸-THC-DMH was more potent but had a slower onset of action than (-) ⁸-THC. Two ways of testing the onset and duration of action were compared. In one procedure (separate tests) the time course of the drug action was established by testing each time interval on separate days with a new injection each test day, whereas in the other procedure (repeated tests) all intervals were evaluated after a single injection. The results were similar for both procedures. The median time intervals for the decay of the (-) ⁸-THC stimulus were 122 and 127 min for the separate and repeated tests procedures respectively. The median time intervals for the onset of action of the (-) ⁹-THC effects of (-) ⁸-THC were 65 and 62 min for the separate and repeated tests procedures respectively. The median time intervals for the decay of (-) ⁸-THC-DMH (0.30 and 0.56 mg/kg) was between 8 and 24 h after injection. Furthermore, a stereoselective action is indicated, as (+) ⁸-THC (5.6 and 10 mg/kg) did not substitute for (-) ⁹-THC.     

2018—2020年郑州市第七人民医院血流感染分离菌的分布及耐药性分析

目的 了解血流感染分离菌的分布及耐药特征,为临床防治血流感染提供指导和依据。方法 收集2018年1月—2020年12月郑州市第七人民医院血培养分离的非重复菌株,采用WHONET5.6软件统计菌株的分布及耐药特征。结果 共分离546株菌株,革兰阴性菌302株（55.31%）,革兰阳性菌220株（40.29%）,真菌24株（4.40%）。前6位分离菌依次为凝固酶阴性葡萄球菌（CNS,23.44%）、大肠埃希菌（18.68%）、肺炎克雷伯菌（14.84%）、金黄色葡萄球菌（6.04%）、鲍曼不动杆菌（4.21%）和铜绿假单胞菌（3.85%）。大肠埃希菌对碳青霉烯类最敏感,肺炎克雷菌碳对美罗培南和亚胺培南的耐药率分别为30.86%和35.80%,鲍曼不动杆菌耐药较严重,耐甲氧西林凝固酶阴性葡萄球菌（MRCNS）和耐甲氧西林金黄色葡萄球菌（MRSA）的检出率分别为72.66%、42.42%,未发现利奈唑胺和万古霉素耐药的葡萄球菌。结论 革兰阴性菌是医院血流感染的主要致病菌,细菌耐药情况复杂,临床要根据药敏结果合理选择抗菌药物。     

A study on the genotoxic activities of some new benzoxazoles

The Bacillus subtilis rec assay has been specially developed to detect DNA-damaging potential in chemicals, with the rationale based on the relative difference of survival of a DNA repair combination proficient strains and its deficient strain, which is interpreted as genotoxicity. The genotoxic activities of newly (1–6) and previously (7–18) synthesized various benzoxazoles and benzimidazoles were analyzed via the B. subtilis rec assay. Newly obtained benzoxazole and benzimidazole derivatives (1–6) were synthesized in the presence of polyphosphoric acid (PPA) and 6 N HCl, respectively to detect their DNA-damaging activities. Among the tested compounds, 6-methyl-2-(o-chlorophenyl)benzoxazole (9), 5-amino-2-(p-methylbenzyl)benzoxazole (4), 5-(p-fluorobenzamido)-2-phenylbenzoxazole (13), and 2-(p-methylaminophenyl)benzoxazole (18) showed genotoxic activities having Rec₅₀ values of 1.85, 1.74, 1.60, and 1.50 or S-probit values of 0.534, 0.482, 0.460, and 0.357, respectively. On the other hand, 2-(p-bromobenzyl)-5-methylbenzimidazole (6) and 2-benzyl-5-(p-fluorophenylacetamido)-benzoxazole (15) were exhibited a reverse effect that displayed a bacterial growth in the rec ^- strains while there was no any bacterial growth in rec ⁺ strains at the same concentration.     

The DNA repair host-mediated assay as a rapid and sensitive in vivo procedure for the determination of genotoxic factors present in various organs of mice

The DNA repair host-mediated assay, in which repairable DNA damage is determined in E. coli cells present in various organs of mice exposed to genotoxic agents, was further developed to broaden the range of organs under study and to simplify the procedure of assessing differential bacterial cell survival. A pair of derivatives of E. coli K-12 strain 343/113 was constructed which differed vastly in DNA repair capacity (uvr ⁺/rec ⁺ vs uvrB/recA), as a means of assessing DNA damaging effects; furthermore, the strains differed in their ability to ferment lactose ( Lac vs Lac ⁺), so that the individual survival of both strains could be determined on a single agar medium (containing neutral red as pH indicator), on which the strains had different colony colour morphology (red, Lac ⁺ vs white, Lac ^– colonies). Finally, the strains were made streptomycin-dependent, to prevent uncontrolled growth of the bacterial cells within the various organs and also to inhibit contamination of the survival agar medium by representatives of the normal intestinal microflora.The experimental procedure consisted of injecting mixtures of stationary cells of the two strains (ca. 3–5×10⁸ viable cells per mouse) both intravenously and orally into mice, either pretreated or subsequently treated with test chemicals. Ninety minutes after injection of the bacteria, the liver, spleen, lungs, kidneys, stomach, intestine, colon, and ca. 50 l blood, were removed, suspended in buffer, homogenized, and the survival of the two strains determined on neutral red agar supplemented with streptomycin.In preliminary experiments in which the mice were treated with intraperitoneal injections of mitomycin C (0–2.0 mg per kg body weight), a dose-dependent increase in DNA damaging activity was induced in bacterial cells present in all organs tested, the lowest effects being observed in kidneys and lungs, and the highest in liver and blood. These results need further confirmation in more extensive tests, but they do nevertheless clearly indicate the possible usefulness of the DNA repair host-mediated assay as a rapid biological dose monitor for obtaining information on the genotoxic activity in vivo of compounds for which long-term mutagenicity and carcinogenicity data are not yet available.     

2016—2018年蚌埠市第一人民医院肺炎克雷伯菌的分布及耐药性分析

目的 分析蚌埠市第一人民医院临床不同标本、不同科室、不同年龄患者分离的肺炎克雷伯菌的耐药情况,为肺炎克雷伯菌的预防和控制提供依据。方法 收集蚌埠市第一人民医院微生物室2016年1月—2018年12月各类临床标本分离的肺炎克雷伯菌,采用生物梅里埃公司Phoenix 100全自动细菌鉴定/药敏仪进行细菌的鉴定和药敏。结果 在检出的382株肺炎克雷伯菌中,分离率居前4位的标本来源是痰液266株（69.6%）、中段尿43株（11.3%）和血液30株（7.9%）;ICU和呼吸内科的分离率最高,分别占34.3%、23.6%;其次是心内科42株,占11.1%;儿科40株,占10.5%;≥65岁患者的分离率最高,占58.9%。其次是15～64岁患者,占31.4%;14岁以下患者最少,占9.7%;肺炎克雷伯菌对氨曲南、头孢他啶、头孢吡肟、左旋氧氟沙星、氨比西林舒巴坦在不同标本、不同科室及不同年龄患者中的耐药率差异显著（P<0.05）;对头孢哌酮舒巴坦、头孢西丁、阿米卡星、亚胺培南、美罗培南的耐药率较低且无统计学差异。结论 通过对临床分离的肺炎克雷伯菌耐药率从不同标本、不同科室、不同年龄患者3个角度进行分析,可以更好的指导临床合理用药,有效的预防和控制耐药菌的蔓延。     

Neurotoxicity and pharmacology of Lathyrus sativus extracts of high- and low-toxicity strains

Neurolathyrism is characterized by spastic paraparesis of the legs. It is caused by overconsumption of grass pea (Lathyrus sativus L.; Leguminosae). We studied toxicity of extracts of L. sativus seeds from two different areas—Bangladesh and Canada—toward rat primary neuron/glia culture. Both extracts showed acute neurotoxicity within 24 h when the 75% ethanol extracts were added to the neuron/glia culture. Fractionation of the extracts showed that the water-soluble fraction accounted for ca. 75–84% of total toxicity in which 3-N-oxalyl-l-2,3-diaminopropanoic acid (l--ODAP) was present at the highest concentration. Toxicity of the water-soluble fraction obtained from Bangladeshi seeds was significantly higher than that obtained from Canada. Effects of these fractions were reversed almost completely by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX), an antagonist of AMPA-receptor. They were partially reversed by group I metabotropic glutamate receptor antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid, or (S)--methyl-4-carboxyphenyl-glycine [(S)-MCPG]. Nitric oxide synthase inhibitor N^G-nitro-l-arginine methyl ester (l-NAME) strongly decreased the extracts toxicity. These data show that the neurotoxicity of grass pea seeds is attributable to l--ODAP, the toxicity of which is mediated by collective effects of l--ODAP on the AMPA-type receptor, metabotropic glutamate receptors, and NO production.     

In vitro mutagenicity of valepotriates

Valepotriates are epoxide-bearing triesters of the monoterpene alcohol 4,7-dimethylcyclopenta-(c)-pyrane isolated from the roots of several Valerianacae species. They are regarded as the main tranquilizing constituents of these drugs.Although the valepotriates valtrate/isovaltrate (VAL) and dihydrovaltrate (DH-VAL) showed a strong alkylating activity against the nucleophilic agent 4-(p-nitrobenzyl)-pyridine (NBP), they were not clearly mutagenic for the strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium or for the strains WP2 and WP2 uvrA^– of Escherichia coli in the absence of a metabolic activation system (S9-mix). However, the valepotriates were mutagenic for TA100, WP2 and WP2 uvrA^– at concentrations up to about 1.0 mole/plate when S9-mix was added to the test system. With more than 1 mole/plate the valepotriates were toxic in the presence of a metabolic activation system for all strains tested. The mutagenicity of the valepotriates was inversely related to the protein content of the S9-mix used. The mutagenicity and toxicity of the valepotriates could be inhibited when the S9-mix was preincubated with the esterase inhibitor paraoxon (1 mM) for 5 min before the test compounds and bacteria were added. Therefore, bioactivation of the valepotriates by an enzymatic hydrolysis of their ester groups is considered. This could be proven by activating the valepotriates with purified esterase.Parts of this paper were presented at the Congress, Fortschritte in der Arzneimittelforschung, April 17–20, 1983 in Munich     

Inhibitory effect of Yunnan traditional medicines on hepatitis C viral polymerase

For the purpose of developing novel anti-hepatitis C virus (HCV) agents from natural resources, 93 Yunnan crude drugs were screened for their inhibitory effects on RNA-dependent RNA polymerase (RdRp) of HCV. Although 71 methanol extracts and 50 water extracts inhibited HCV-RdRp by more than 50% at a concentration of 50 g/ml, the majority of them contained a high percentage of tannins. However, methanol extracts of Plumbago zeylanica (branch), Maytenus fookerii (leaf) and Huashidancha (Y61, branch and leaf), and water extracts of Potentilla griffithii (whole plant) and Salvia yunnanensis (underground part), having IC₅₀ values of less than 10 g/ml, showed less than 10% tannin content. In addition, from a methanol extract of Tripterygium hypoglaucum (root bark), demethylzeylasteral was isolated as a strongly inhibitory substance against HCV-RdRp.     

Biochemical and functional properties of a thrombin-like enzyme isolated from Bothrops pauloensis snake venom

In the present study, a thrombin-like enzyme named BpSP-I was isolated from Bothrops pauloensis snake venom and its biochemical, enzymatic and pharmacological characteristics were determined. BpSP-I is a glycoprotein that contains both N-linked carbohydrates and sialic acid in its structure, with M_r = 34,000 under reducing conditions and pI  6.4. The N-terminal sequence of the enzyme (VIGGDECDINEHPFL) showed high similarity with other thrombin-like enzymes from snake venoms. BpSP-I showed high clotting activity upon bovine and human plasma and was inhibited by PMSF, benzamidine and leupeptin. Moreover, this enzyme showed stability when examined at different temperatures (−70 to 37 °C), pH values (3–9) or in the presence of divalent metal ions (Ca²⁺, Mg²⁺, Zn²⁺ and Mn²⁺). BpSP-I showed high catalytic activity upon substrates, such as fibrinogen, TAME, S-2238 and S-2288. It also showed kallikrein-like activity, but was unable to act upon factor Xa and plasmin substrates. Indeed, the enzyme did not induce hemorrhage, myotoxicity or edema. Taken together, our data showed that BpSP-I is in fact a thrombin-like enzyme isoform isolated from Bothrops pauloensis snake venom.     

2018—2019年西安交通大学第二附属医院鲍曼不动杆菌的分布及耐药性分析

目的 分析西安交通大学第二附属医院鲍曼不动杆菌的临床分布及耐药性,为临床医师选择合理的抗感染治疗方案提供参考依据。方法 以2018年1月-2019年12月西安交通大学第二附属医院住院的患者为研究对象,按照美国临床实验室标准化委员会（CLSI）推荐的方法进行鲍曼不动杆菌的初步筛选,用梅里埃VITEK 2 Compact全自动细菌鉴定及药敏分析系统进行细菌鉴定和药敏实验,用Excel进行数据统计分析。结果 2018-2019年本院住院患者中共分离出935株鲍曼不动杆菌,主要分布于急诊科,共181株;主要来源于痰液标本,共676株。感染人群主要为14岁以上的中青年及老年患者。药敏结果显示鲍曼不动杆菌对替卡西林/克拉维酸、多西环素、哌拉西林/他唑巴坦具有较高的耐药性,耐药率依次为87.43%、75.96%、64.98%;鲍曼不动杆菌对黏菌素、阿米卡星和替加环素具有良好的敏感性,敏感率依次为99.61%、85.02%、73.56%。结论 本院临床上鲍曼不动杆菌感染的高发人群为14岁以上的中青年及老年患者,鲍曼不动杆菌对多种抗生素都有很强的耐药性,应加强病原菌培养及耐药性监测,指导临床医师合理使用抗生素。     

Some pharmacological properties of Wy 27127 a more selective alpha2: alpha1-adrenoceptor antagonist than idazoxain in vitro

Summary Wy 27127 and idazoxan were approximately equipotent as antagonists at ₂-adrenoceptors as estimated by their ability to block clonidine-induced inhibition of electrically-evoked contractions of the rat isolated vas deferens.Idazoxan was seven times as potent as Wy 27127, as an antagonist at ₁-adrenoceptors as indicated by blockade of methoxamine-induced contractions of the rat isolated anococcygeus muscle.Thus, the ₂: ₁ selectivity ratio, as calculated from these tests was 407 for Wy 27127 and 76 for idazoxan.Wy 27127 and idazoxan were equipotent in enhancing stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [³H]-noradrenaline as expected for ₂-adrenoceptor antagonists. At higher concentrations both compounds reduced the stimulation-evoked contraction of the pulmonary artery but idazoxan was 15 times as potent as Wy 27127 in this respect.Neither compound had marked antagonist actions at 5-hydroxytryptamine (D), muscarinic, presynaptic dopamine or histamine (H₁) receptors or at ₁-adrenoceptors.Thus, idazoxan and Wy 27127 were equipotent ₂-adrenoceptor antagonists in vitro, however, the ₂: ₁ selectivity of Wy 27127 was considerably greater than that of idazoxan by virtue of weaker ₁-adrenoceptor antagonism.     

Mutagenic activity of cytostatic methyl hydrazones with different strains of Salmonella typhimurium

Experiments are performed to ascertain the mutagenic properties of four new cytostatic methyl-hydrazones in the Ames test using different strains of Salmonella typhimurium. As could be demonstrated all four hydrazones are mutagenic per se without a metabolic activation through rat liver microsomes (S-9 fraction). Whereas the -chloroethyl hydrazones B1 and B2 cause a base-pair substitution with the strains TA100 and TA1535 the methyl-hydrazones EB4 and CyB4 both cause base-pair substitution with TA100 and frameshift mutation with TA98. At both strains the mutagenic activity of CyB4 ist powerful. Furthermore, no relation could be detected between the mutagenic properties of the methyl-hydrazones and their alkylating behaviour on 4-(4-nitrobenzyl)-pyridine.     

The Biology of Oreochromis niloticus in a Polluted Canal

In the present investigation, length–weight relationship, condition factor, age, growth, mortality, gonadosomatic index (GSI) and fecundity of tilapias (Bolti in Arabic): Oreochromis niloticus, from Shanawan drainage canal (SDC), Al-Minufiya Province, Egypt, were studied. This was carried out on 162 fish samples collected during the period from April 1992 to May 1993. Oreochromis niloticus was found to attain sexual maturity early (8–9cm), was more fecund (1,234–3,893) and has high mortality rates (91% for males and 94% for females). A comparison of the various parameters of O. niloticus from SDC with those of other authors in different localities and times in Egypt revealed year-to-year and geographically significant differences in relation to variation in weight with length, condition factor, fecundity, growth and mortality rates. These differences were discussed and were found to be attributed to the effect of eutrophication and pollution on the growth, age and other biological aspects of O. niloticus. Multiple regression analysis showed that only female GSI correlated significantly with pesticides and heavy metals contamination.     

Lyophilized Paclitaxel Magnetoliposomes as a Potential Drug Delivery System for Breast Carcinoma via Parenteral Administration: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">in Vivo</Emphasis> Studies

No HeadingPurpose. The study reports in vitro and biological evaluation of lyophilized negatively charged paclitaxel magnetic liposomes as a potential carrier for breast carcinoma via parenteral administration.Methods. Paclitaxel in magnetoliposomes were extracted by centrifugation and quantified by high-performance liquid chromatography (HPLC). Biological properties were studied using pharmacokinetics, in vivo distribution and cytotoxicity assays, as well as a mouse model of EMT-6 breast cancer.Methods. Pharmacokinetic studies showed that encapsulation of paclitaxel in magnetoliposomes produced marked difference over the drug in Cremophor EL/ethanol pharmacokinetics, with an increased t_1/2 19.37 h against 4.11 h. For in vivo distribution, paclitaxel concentration of lyophilized magnetoliposomes in the tumor was much higher than that of lyophilized conventional liposomes or Cremophor EL/ethanol, whereas in heart it was much lower than the latter two formulations via s.c. and i.v. administration. Lyophilized paclitaxel magnetic liposomes showed more potency on the therapy of breast cancer than other formulations via s.c. and i.p. administration.Conclusions. The current study demonstrates that paclitaxel magnetoliposomes can effectively be delivered to tumor and exert a significant anticancer activity with fewer side effects in the xenograft model.