Molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against Oncomelania hupensis in hilly regions / 中国血吸虫病防治杂志

Objective To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect. Methods The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m2) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m2 in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m2, and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m2, while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m2, and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m2. Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group. Results The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m2 and 56.25 g/m2 in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m2 and 1.03 Yuan per m2 in groups A, B, C and D, respectively. Conclusions The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.

Innovative pharmaceutical strategies for niclosamide repositioning / Estratégias farmacêuticas inovadoras para o reposicionamento da niclosamida

The antiparasitic niclosamide has shown promising anticancer activity in preclinical studies against several types of cancer, such as colorectal and prostate. Thus, the objective of this work was to develop innovative formulations for the repositioning of niclosamide as an anticancer agent. In chapter I, a critical review of the literature on the physicochemical properties of the drug was carried out, in addition the results of clinical studies against colorectal and prostate cancer. Besides, a review was carried out on studies that developed formulations containing this drug, as well as hypotheses to improve the biopharmaceutical performance of this molecule. In chapter II, the development of solid amorphous dispersion containing niclosamide was carried out. Drug/polymer solutions were acoustic levitated and characterized by synchrotron X-ray light. This set allowed fast, high quality measurements, as well as the identification of niclosamide recrystallization. Plasdone® and Soluplus® demonstrated better properties to form amorphous dispersions, with the latter showing superior solubility enhancement. The study showed that the developed formulation increased the apparent saturation solubility of niclosamide in water by two times. In chapter III the objective was the development, physicochemical characterization and in vitro anticancer activity of a niclosamide nanoemulsion, having HCT-116 cells as a cellular model. Preliminary results indicated Capmul® MCM C8 as the best liquid lipid for the system, but the first nanoemulsions containing this lipid were not stable to justify its usage. On the other hand, Miglyol® 812 indicated to be a suitable liquid lipid for the system. The niclosamide nanoemulsion (~200 nm) with Miglyol® 812 and poloxamer 188 was stable for 56 days, with a monomodal particle size distribution. Cell viability assay against HCT-116 cells demonstrated that niclosamide cytotoxicity is time and concentration dependent. Results herein obtained encourage further research to understand and optimize niclosamide performance as an anticancer drug substance

O antiparasitário niclosamida tem apresentado promissora atividade anticâncer em estudos pré- clínicos contra diversos tipos de câncer, como coloretal e próstata. Assim, o objetivo deste trabalho foi desenvolver formulações inovadoras para o reposicionamento da niclosamida como agente anticâncer. No capítulo I foi realizada revisão crítica da literatura sobre as propriedades físico-químicas do fármaco, além de resultados de estudos clínicos da niclosamida contra câncer de coloretal e de próstata. Além disso, foi feita revisão sobre estudos que desenvolveram formulações contendo esse fármaco, bem como hipóteses para melhorar o desempenho biofarmacêutico dessa molécula. No capítulo II foi realizado o desenvolvimento de dispersão solida amorfa contendo niclosamida. Soluções de fármaco/polímero foram levitadas em levitador acústico e caracterizadas por raios-X de luz síncrotron. Este conjunto permitiu medições rápidas e de alta qualidade, bem como identificação de recristalização da niclosamida. Plasdone® e Soluplus® demonstraram melhores propriedades para formar as dispersões amorfas, com o último apresentando aumento de solubilidade superior. O estudo mostrou que a formulação desenvolvida aumentou em duas vezes a solubilidade aparente de saturação da niclosamida em água. No capítulo III o objetivo foi o desenvolvimento, a caracterização físicoquímica e atividade anticâncer in vitro de uma nanoemulsão de niclosamida, tendo células HCT-116 como modelo celular. Resultados preliminares indicaram o Capmul® MCM C8 como o melhor lipídio líquido para o sistema, mas as primeiras nanoemulsões contendo este lipídio não foram estáveis para justificar seu uso. Por outro lado, Miglyol® 812 indicou ser um lipídio líquido adequado para o sistema. A nanoemulsão de niclosamida (~200 nm) com Miglyol® 812 e poloxâmero 188 foi estável por 56 dias, com distribuição monomodal do tamanho de partícula. O ensaio de viabilidade celular contra células HCT-116 demonstrou que a citoxicidade da niclosamida é dependente do tempo e da concentração. Os resultados aqui obtidos encorajam mais pesquisas para entender e otimizar o desempenho da niclosamida como uma substância anticancerígena

Effectiveness and cost analysis of two chemical molluscicides in hilly schistosomiasis-endemic regions / 中国血吸虫病防治杂志

Objective To investigate the effectiveness and cost of 50% and 80% wettable powder of niclosamide ethanolamine salt (NESWP) and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in hilly schistosomiasis-endemic regions, so as to provide insights into the selection of chemical molluscicides in hilly regions. Methods In September 2020, a wasteland in Guanshanqiao Village, Yanrui Township, Yushan County of Jiangxi Province was selected as the experimental region, which was sectioned into five blocks and defined as four experimental groups (A1, A2, B, C) and a blank control group (D). 80% NESWP were given at doses of 1 g/m2 and 1.5 g/m2 in groups A1 and A2 using the spraying method, 50% NESWP was given at a dose of 2 g/m2 in Group B using the spraying method, and 26% MNSC was at a dose of 4 g/m2 in Group C using the spraying method, while no chemical treatment was given in Group D. Snail survey was performed using a systematic sampling method before chemical treatment and 1, 3, 7 d and 15 d post-treatment to examine the molluscicidal effect, and all molluscicidal costs were estimated to calculate the cost of chemical treatment per 1 m2 and the cost of the reduction in the mean density of living snails per 1%. Results The highest mortality of snails was 78.95% and the lowest density of living snails was 0.2388 snails/0.1 m2 in the experimental groups within 7 d of chemical treatment, and the highest mortality of snails was 94.74% and the lowest density of living snails was 0.058 0 snails/0.1 m2 7 d post-treatment. There were no significant differences in the snail mortality among the A1, A2, B and C groups 1 (χ2 = 2.250, P > 0.05), 3 (χ2 = 1.779, P > 0.05) or 15 d post-treatment (χ2 = 2.286, P > 0.05), while a significant difference was detected in the snail mortality among the four groups 7 d post-treatment (χ2 = 7.990, P = 0.046). In addition, there were no significant differences in the snail mortality between A1 and A2 groups 1 (χ2 = 0.724, P > 0.05), 3 (χ2 = 0.584, P > 0.05), 7 (χ2 = 0.400, P > 0.05) or 15 d post-treatment (χ2 = 0.251, P > 0.05). The costs of chemical treatment per 1 m2 were 0.58, 0.60, 0.64 Yuan and 0.73 Yuan in groups A1, A2, B and C, and the costs of the mean density of living snail per 1% reduction were 19.29, 20.44, 21.68 Yuan and 23.53 Yuan in groups A1, A2, B and C, respectively. Conclusion 80% NESWP shows a high molluscicidal efficacy and low cost in hilly schistosomiasis-endemic regions.

Molluscicidal effect of immersion with 50% wettable powder of niclosamide ethanolamine salt against Oncomelania hupensis on the soil surface and inside the soil layer in winter / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal effect of 50% wettable powder of niclosamide ethanolamine salt (WPNES) against Oncomelania hupensis on the soil surface and inside the soil layer by immersion method in winter. Methods O. hupensis snails were placed on the soil surface and 2, 5 cm and 10 cm under the soil layer outdoors in winter, and then immersed in 50% WPNES at concentrations of 1 mg/L and 2 mg/L for 1, 3 d and 7 d, while dechlorinated water served as controls. Snail mortality was observed following immersion with 50% WPNES on the soil surface and inside the soil layer. Results Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 3-day corrected snail mortality rates were 98.0% and 76.0% on the soil surface, and the 7-day corrected snail mortality rate was both 100.0%. Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 7-day corrected snail mortality rates were 95.5% and 85.6% 2 cm below the soil layer, 66.0% and 6.4% 5 cm below the soil layer. However, the 7-day snail mortality rate swere comparable between the 50% WPNES treatment group (at 2 mg/L and 1 mg/L) and controls 10 cm below the soil layer (both P > 0.05). Conclusion Immersion of 50% WPNES at a concentration of 2 mg/L for 7 days presents a high molluscicidal efficacy against O. hupensis on the soil surface and 5 cm within the soil layers in winter.

Study on the factors affecting the degradation of niclosamide in the soil / 中国血吸虫病防治杂志

ObjectiveTo investigate the factors affecting the degradation of niclosamide in the soil, so as to provide the evidence for the assessment of the environmental safety in the field snail control with niclosamide. MethodsA high performance liquid chromatography was established for the determination of niclosamide in the field. Then, the degradation of niclosamide was investigated in soils with different moistures (10%, 30%, 50%, 70% and 90%), temperatures [(15 ± 1), (25 ± 1), (35 ± 1) °C], initial concentrations (1, 5, 10 mg/kg) and in sterilized and non-sterilized soils. In addition, the degradation of niclosamide was fitted with the first-order kinetics equation, and the degradation half-life was calculated. Results The niclosamide residues gradually decreased over time in soils with different moistures, and a higher rate of degradation was seen in soils with a higher moisture. The degradation half-life of niclosamide reduced from 4.258 d in the soil with a 10% moisture to 2.412 d in the soil with a 90% moisture. The niclosamide residues gradually decreased over time in soils with different temperatures, and a higher rate of degradation was seen in soils with a higher temperature. The degradation half-life of niclosamide reduced from 4.398 d in the soil with a temperature of (15 ± 1) °C to 2.828 d in the soil with a temperature of (35 ± 1) °C. The degradation half-lives of niclosamide were 3.212, 3.333 d and 3.448 d in soils containing niclosamide at initial concentrations of 1, 5 mg/kg and 10 mg/kg, and > 30 d and 3.273 d in sterilized and non-sterilized soils. Multiple linear regression analysis revealed that soil microorganisms (P = 0.010), moisture (P = 0.000) and temperature (P = 0.002) affected the half-life of niclosamide degradation. Conclusions The degradation of niclosamide in soils fits the first-order kinetics equation, and presence of microorganisms, a high temperature and high moisture may accelerate the degradation of niclosamide in the soil.

The effect of Niclosamide in acetic acid induce colitis: an experimental study

Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon for which a lot of treatment modalities are present. However, significant side effects are associated with them, and there is a need for a search for other tretment options. This study was aimed to assess the contribution of niclosamide in experimentally established colitis in rats. Animals were categorized into 5 groups; the control group undergoes no induction of UC, colitis group in which UC was induced, and animals receive no treatment, the niclosamide group that received niclosamide and sulfasalazine group that received sulfasalazine. Each group was composed of 10 animals. After the completion of a one-month period of the experiment animals were sacrificed and the following meausres were done: the weight of the colon, determination of the area of mucosal damage by mm2, histological scoring after hematoxylin and eosin stain together with MAC score and immunohistochemistry of IL-6, TNF-alpha, MPO, MDA, CD62, and ICAM1. The results of the current study revealed that Nicosamide was able to reduce the area of mucosal damage, colon weight, histological and Mac scores and immunohistochemical scores of inflammatory and oxidative markers, significantly when contrasted to a group of colitis (P< 0.05). It has been concluded that Niclosamide was proved to have a significant effect as an adjuvant mode of therapy for colitis through its, anti-inflamatory and anti-oxidant effects (AU)

Comparison of molluscicidal cost and effectiveness between 5% niclosamide ethanolamine salt granules and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt / 中国血吸虫病防治杂志

Objective To compare the molluscicidal effects and cost-effectiveness of 5% niclosamide ethanolamine salt granules (NEG) and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt (MNSC) . Methods Two plots with high Oncomelania hupensis snail density were selected as research areas in Nanjing Chemical Industry Zone, and 5% NEG (40 g/m2) and 26% MNSC (40 g/m2) were used by the spraying method for snail control in the two plots, and their molluscicidal effects and cost-effectiveness were investigated and statistically analyzed. Results There was no significant difference between 5% NEG and 26% MNSC in the molluscicidal effects. The cost of 5% NEG was 1.25 times higher than that of 26% MN-SC per ten thousand square meters in snail control. Conclusions The cost of 5% NEG is higher than that of 26% MNSC per ten thousand square meters in snail control. Their molluscicidal effects are similar.

Effectiveness of snail control by immersion of molluscicides through tide diversion in marshlands: a field evaluation / 中国血吸虫病防治杂志

Objective To compare the effectiveness of snail control between immersion of molluscicides through tide diversion and mollusciciding by spraying in marshland areas. Methods Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion and spraying 26% suspension concentrate of metaldehyde and niclosamide alone were employed for snail control in two neighboring snail-breeding marshlands, and snails were surveyed before and after mollusciciding. The mortality of snails and the density of living snails were estimated. Results The density of living snails reduced by 72.19% and 100.00% 1 and 2 years after immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion, and 5.93% and 18.15% 1 and 2 years after spraying 26% suspension concentrate of metaldehyde and niclosamide alone. Conclusion Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion is significantly superior to spraying 26% suspension concentrate of metaldehyde and niclosamide along for snail control, and implementation of immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion for more than 2 successive years may achieve a higher snail control efficiency.

Effect and cost-effectiveness of three commonly used molluscicides in largescale field application / 中国血吸虫病防治杂志

Objective To evaluate the effect and cost-effectiveness of three commonly used molluscicides, 4% "Luo-wei" (tea-seed distilled saponins, TDS), 50% niclosamide ethanolamine salt wettable powder (NESWP), and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in large-scale field application, so as to provide the references for formulating the strategy of snail control. Methods The field test and parallel comparison were implemented. A marshland with Oncomelania hupensis snails of the Yangtze River was divided into 4 parts (10 hm2) for the research, and three of them were experimental areas while the last one was a blank control area. The experimental areas were sprayed with 4% "Luo-wei", 50% NESWP and 26% MNSC respectively for 3 times and the interval was 1 week. Seven days after each spraying the effect of snail control was investigated, and the costs of molluscicides, labor, transportation, fuel consumption and mechanical loss were recorded. The cost of each molluscicide, snail mortality, snail density, and the cost of increasing 1% of snail mortality per 100 m2 were analyzed and compared. Results After the first, second and third spraying, the corrected snail mortality rates were 67.34%, 76.55% and 84.60% respectively in the 4% "Luo-wei" group; the corrected snail mortality rates were 64.71%, 75.17% and 83.89% respectively in the 50% NESWP group; the corrected snail mortality rates were 66.55%, 76.27% and 86.67% respectively in the 26% MNSC group. There was no significant difference among the 3 groups in the snail mortality at the same spraying time (χ2 = 1.590, 0.571, 3.238, all P > 0.05) . In addition, along with the increase of the spraying times, the snail mortality of each group was increased significantly compared to that of the control group (χ2 = 79.333, 94.718, 117.020, all P < 0.01) . After the first, second and third spraying, the reduction rates of snail density were 69.82%–86.60% in the 4% "Luo-wei" group, 68.66%–86.55% in the 50% NESWP group, and 71.89%–88.87% in the 26% MNSC group respectively. The decreasing amplitude of the snail density was more than 85% in all the experimental areas after 3 rounds of spraying molluscicide. The snail control costs per 100 hm2 were 19.57, 11.97 Yuan and 10.47 Yuan in the 4% "Luo-wei" group, 50% NESWP group, and 26% MNSC group respectively. After the first, second and third spraying, the costs of increasing 1% of snail mortality per 100 m2 were 0.30, 2.08 Yuan and 2.38 Yuan in the 4% "Luo-wei" group, 0.20, 1.10 Yuan and 1.32 Yuan in the 50% NESWP group, and 0.17, 1.04 Yuan and 0.97 Yuan in the 26% MNSC group respectively, and the cost-effectiveness was the highest at the first spraying in all the three groups. Conclusions The effects of the three molluscicides for snail control are similar, but the efficacy of snail control is reduced as the spraying time increases.

Effectiveness of snail control by immersion of molluscicides through tide diversion in marshlands: a field evaluation / 中国血吸虫病防治杂志

Objective To compare the effectiveness of snail control between immersion of molluscicides through tide diversion and mollusciciding by spraying in marshland areas. Methods Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion and spraying 26% suspension concentrate of metaldehyde and niclosamide alone were employed for snail control in two neighboring snail-breeding marshlands, and snails were surveyed before and after mollusciciding. The mortality of snails and the density of living snails were estimated. Results The density of living snails reduced by 72.19% and 100.00% 1 and 2 years after immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion, and 5.93% and 18.15% 1 and 2 years after spraying 26% suspension concentrate of metaldehyde and niclosamide alone. Conclusion Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion is significantly superior to spraying 26% suspension concentrate of metaldehyde and niclosamide along for snail control, and implementation of immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion for more than 2 successive years may achieve a higher snail control efficiency.

Effect of niclosamide on thyroid endocrine system of larval zebrafish / 中国血吸虫病防治杂志

Objective To examine the effect of niclosamide on thyroid endocrine disruption in larval zebrafish. Methods Zebrafish embryos (2 hours post-fertilization) were exposed to niclosamide at concentrations of 0, 5, 10, 20, 40 μg/L and 80 μg/L until 120 hours post-fertilization, and the body weight, hatching rate, malformation rate and survival rate of zebrafish embryos/larvae were measured. In addition, the triiodothyronine (T3) and thyroxin (T4) activities were determined in zebrafish, and the expression of tshβ and ttr genes that were associated with the regulation of thyroid hormones was quantified using a quantitative real-time PCR (qPCR) assay. Results Following exposure to niclosamide, there was no concentration-dependent hatching rate (F = 0.947, P = 0.924) or body weight of larval zebrafish (F = 1.042, P = 0.409); however, there were concentration-dependent survival rate (F = 9.309, P = 0.005) and malformation rate (F = 14.900, P = 0.001). As compared to controls, exposure to niclosamide at concentrations of 40 μg/L and 80 μg/L resulted in a significant reduction in the survival rate (both P values < 0.05), and a marked rise in the malformation rate of larval zebrafish (both P values < 0.05). In addition, the T4 activity increased (R2 = 0.927, F = 6.858, P = 0.003) and T3 activity decreased (R2 = 0.925, F = 8.212, P = 0.001) in larval zebrafish with the concentration of niclosamide. qPCR assay determined up-regulation of tshβ gene expression (R2 = 0.840, F = 9.032, P = 0.002) and down-regulation of ttr gene expression (R2 = 0.952, F = 9.130, P = 0.002). Conclusions Niclosamide exposure at environmental related concentrations may cause thyroid endocrine disruption of larval zebrafish.

Effect and cost-effectiveness of three commonly used molluscicides in largescale field application / 中国血吸虫病防治杂志

Objective To evaluate the effect and cost-effectiveness of three commonly used molluscicides, 4% "Luo-wei" (tea-seed distilled saponins, TDS), 50% niclosamide ethanolamine salt wettable powder (NESWP), and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in large-scale field application, so as to provide the references for formulating the strategy of snail control. Methods The field test and parallel comparison were implemented. A marshland with Oncomelania hupensis snails of the Yangtze River was divided into 4 parts (10 hm2) for the research, and three of them were experimental areas while the last one was a blank control area. The experimental areas were sprayed with 4% "Luo-wei", 50% NESWP and 26% MNSC respectively for 3 times and the interval was 1 week. Seven days after each spraying the effect of snail control was investigated, and the costs of molluscicides, labor, transportation, fuel consumption and mechanical loss were recorded. The cost of each molluscicide, snail mortality, snail density, and the cost of increasing 1% of snail mortality per 100 m2 were analyzed and compared. Results After the first, second and third spraying, the corrected snail mortality rates were 67.34%, 76.55% and 84.60% respectively in the 4% "Luo-wei" group; the corrected snail mortality rates were 64.71%, 75.17% and 83.89% respectively in the 50% NESWP group; the corrected snail mortality rates were 66.55%, 76.27% and 86.67% respectively in the 26% MNSC group. There was no significant difference among the 3 groups in the snail mortality at the same spraying time (χ2 = 1.590, 0.571, 3.238, all P > 0.05) . In addition, along with the increase of the spraying times, the snail mortality of each group was increased significantly compared to that of the control group (χ2 = 79.333, 94.718, 117.020, all P < 0.01) . After the first, second and third spraying, the reduction rates of snail density were 69.82%–86.60% in the 4% "Luo-wei" group, 68.66%–86.55% in the 50% NESWP group, and 71.89%–88.87% in the 26% MNSC group respectively. The decreasing amplitude of the snail density was more than 85% in all the experimental areas after 3 rounds of spraying molluscicide. The snail control costs per 100 hm2 were 19.57, 11.97 Yuan and 10.47 Yuan in the 4% "Luo-wei" group, 50% NESWP group, and 26% MNSC group respectively. After the first, second and third spraying, the costs of increasing 1% of snail mortality per 100 m2 were 0.30, 2.08 Yuan and 2.38 Yuan in the 4% "Luo-wei" group, 0.20, 1.10 Yuan and 1.32 Yuan in the 50% NESWP group, and 0.17, 1.04 Yuan and 0.97 Yuan in the 26% MNSC group respectively, and the cost-effectiveness was the highest at the first spraying in all the three groups. Conclusions The effects of the three molluscicides for snail control are similar, but the efficacy of snail control is reduced as the spraying time increases.

Molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands. Methods The molluscicidal effects of spraying with 25% suspension concentrate of niclosamide ethanolamine salt (25% SCN) and 50% wettable powder formulation of niclosamide ethanolamine salt (50% WPN), and dusting with 4% niclosamide ethanolamine salt dustable powder (4% DP) for controlling Oncomelania hupensis snails were investigated and compared in the fields, and the cost-effectiveness was analyzed. Results The corrected mortalities and the reduced rates of density of snails were 54.37%, 91.70%, 92.76%, 79.50%, and 59.55%, 95.93%, 97.63%, 94.15%, respectively, on 3, 7, 15, 30 d after spaying with 25% SCN, those on 3, 7, 15, 30 d after dusting with 4% DP were 59.10%, 91.83%, 95.56%, 93.34% and 65.03%, 94.93%, 97.61%, 97.28%, respectively; and those on 3, 7, 15, 30 d after spraying with 50% WPN were 76.29%, 91.68%, 93.12%, 81.59% and 81.24%, 97.02%, 97.84%, 95.27%, respectively. The cost of spraying with 25% SCN was 0.21 Yuan/m2, that of dusting with 4% DP was 0.39 Yuan/m2, and that of spraying with 50% WPN was 0.23 Yuan/m2 for snail control in the marshland. The cost of reduced one percentage of the corrected mortalities and the density of snails in controlling snails by 25% SCN, 4% DP and 50% WPN on 15 d were 22.68, 40.63, 25.17 Yuan and 21.54, 39.78, 23.95 Yuan, respectively. Conclusions The three different formulations of niclosamide are reliable and effective for snail control in marshlands. There are some differences among the different molluscicides in start time, pharmacodynamic characteristics, spraying methods in the field, cost of snail control, and influencing factors. Therefore, we need reasonably select the suitable molluscicides according to the environmental characteristics and working condition.

Molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands. Methods The molluscicidal effects of spraying with 25% suspension concentrate of niclosamide ethanolamine salt (25% SCN) and 50% wettable powder formulation of niclosamide ethanolamine salt (50% WPN), and dusting with 4% niclosamide ethanolamine salt dustable powder (4% DP) for controlling Oncomelania hupensis snails were investigated and compared in the fields, and the cost-effectiveness was analyzed. Results The corrected mortalities and the reduced rates of density of snails were 54.37%, 91.70%, 92.76%, 79.50%, and 59.55%, 95.93%, 97.63%, 94.15%, respectively, on 3, 7, 15, 30 d after spaying with 25% SCN, those on 3, 7, 15, 30 d after dusting with 4% DP were 59.10%, 91.83%, 95.56%, 93.34% and 65.03%, 94.93%, 97.61%, 97.28%, respectively; and those on 3, 7, 15, 30 d after spraying with 50% WPN were 76.29%, 91.68%, 93.12%, 81.59% and 81.24%, 97.02%, 97.84%, 95.27%, respectively. The cost of spraying with 25% SCN was 0.21 Yuan/m2, that of dusting with 4% DP was 0.39 Yuan/m2, and that of spraying with 50% WPN was 0.23 Yuan/m2 for snail control in the marshland. The cost of reduced one percentage of the corrected mortalities and the density of snails in controlling snails by 25% SCN, 4% DP and 50% WPN on 15 d were 22.68, 40.63, 25.17 Yuan and 21.54, 39.78, 23.95 Yuan, respectively. Conclusions The three different formulations of niclosamide are reliable and effective for snail control in marshlands. There are some differences among the different molluscicides in start time, pharmacodynamic characteristics, spraying methods in the field, cost of snail control, and influencing factors. Therefore, we need reasonably select the suitable molluscicides according to the environmental characteristics and working condition.

Comparison of molluscicidal cost and effectiveness between 5% niclosamide ethanolamine salt granules and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt / 中国血吸虫病防治杂志

Objective To compare the molluscicidal effects and cost-effectiveness of 5% niclosamide ethanolamine salt granules (NEG) and 26% suspension concentrate of metalaldehyde and niclosamide ethanolamine salt (MNSC) . Methods Two plots with high Oncomelania hupensis snail density were selected as research areas in Nanjing Chemical Industry Zone, and 5% NEG (40 g/m2) and 26% MNSC (40 g/m2) were used by the spraying method for snail control in the two plots, and their molluscicidal effects and cost-effectiveness were investigated and statistically analyzed. Results There was no significant difference between 5% NEG and 26% MNSC in the molluscicidal effects. The cost of 5% NEG was 1.25 times higher than that of 26% MN-SC per ten thousand square meters in snail control. Conclusions The cost of 5% NEG is higher than that of 26% MNSC per ten thousand square meters in snail control. Their molluscicidal effects are similar.

Field molluscicidal effect of water-free formulations of niclosamide ethanolamine salt against Oncomelania hupensis snails in a marshland / 中国血吸虫病防治杂志

To evaluate the molluscicidal effects of various water-free formulations of niclosamide ethanolamine salt against Oncomelania hupensis in the field of marshlands along the Yangtze River.The river beach with O. hupensis snails were selected as the test field in the marshland along the Yangtze River in Pukou District, Nanjing City. A molluscicidal experiment was carried out by the mechanical dusting method with the dustable powder (DP), powder-granule (PG), granule (GR) of niclosamide ethanolamine salt respectively. The snail mortality, corrected mortality, and the reduced rate of snails’ density were parallel compared among DP, PG and GR.On the 3rd day after the dusting, the snail mortality rates were 66.67%, 67.24%, and 66.87% in the DP, PG, and GR groups respectively, on the 7th day after the dusting, the snail mortality rates were 75.36%, 79.73%, and 73.97% in the DP, PG, and GR groups respectively, and there was no significant difference among the groups (χ2 = 0.006, 0.895, both P > 0.05). On the 15th day after the dusting, the snail mortality rates were 86.92%, 72.86%, and 71.43% in the DP, PG, and GR groups respectively, and there was a significant difference among the groups (χ2 = 9.709, P < 0.01). The snail mortality in the DP group was significantly higher than that in the PG, and GR groups. The curves of the snail corrected mortality and reduced rate of snails’density presented steadily rising trends in the DP group, but presented falling trends in the PG and GR groups on the 15th day after the dusting.The molluscicidal effect of DP is stable and effective in the marshland along the Yangtze River, but the drift of the powder is still not effectively controlled. It is necessary that the different dosage forms are perfected.

Vasorelaxant effect and mechanism of niclosamide ethanolamine on rat coronary artery / 中国比较医学杂志

Objective To investigate the vasorelaxant effect and possible mechanism of niclosamide ethanolamine (NEN)on isolated rat coronary artery(RCA). Methods Wire myograph was used to record myogenic tone of vessels. The vasorelaxant effect of NEN was studied in RCA precontracted with either KCl or U46619. Study of related inhibitors was performed to investigate possible involvement of potassium channels and the mitogen-activated protein kinase(MAPK) signaling pathway in vasorelaxation. The effect of NEN on Ca2+mobilization was determined by observing vasoconstrictor-induced contractions in tissue solution deprived of Ca2+followed by Ca2+restoration. Results NEN(0.5-3.0 μmol/L) relaxed RCA precontracted with KCl or U46619 in a concentration-dependent manner. MAPK inhibitors(PD98059 and SB239063)reduced the relaxant effect of NEN,while the potassium-channel blockers(tetraethylamine,4-aminopyridine, BaCl2,and glibenclamide)did not significantly affect relaxation. NEN specifically inhibited the contraction component dependent on extracellular Ca2+influx in vessels stimulated with KCl and U46619, with a negligible effect on the component dependent on intracellular Ca2+release. Conclusions NEN exhibits vasodilator properties in RCA. Inhibition of extracellular Ca2+influx and activation of the MAPK signaling pathway may be involved in NEN-induced RCA vasorelaxation.

Inhibitory effect of combined niclosamide and cisplatin on adrenocortical carcinoma xenografts in nude mice / 中国肿瘤临床

Objective:To examine the inhibitory effect and mechanism of niclosamide combined with low-dose cisplatin on adrenocor-tical carcinoma xenografts in nude mice. Methods:A SW-13 cell transplanted tumor model was first established in nude mice. The nude mice were then divided into the control group, niclosamide group, cisplatin group, and combined drug group. The groups were compared in terms of tumor body volume, tumor weight, and biochemical index. The cell apoptosis rate of the transplanted tumor tis-sue was detected by TUNEL assay, while Bcl-2 and caspase-3 protein expression in the transplanted tumor tissue was detected by im-munohistochemistry and Western blot. Results:The terminal tumor volume and weight of the combined drug group were lower than those of the niclosamide and cisplatin groups (all P0.05). TUNEL test results showed that the cell apoptotic rate of the combined drug group was higher than that of the niclosamide group (P=0.004) and cisplatin group (P=0.005). Immunohistochemistry and West-ern blot test results showed that Bcl-2 expression in the combined drug group was lower than those of the niclosamide and cisplatin groups (all P<0.001), while caspase-3 expression in the combined drug group was the highest among those of other groups (all P<0.001). Conclusion:Niclosamide can enhance the inhibitory effect of low-dose cisplatin on the growth of adrenocortical carcinoma and has no additional side effects. This enhancement is probably related to the influence of niclosamide on Bcl-2 and caspase-3 expres-sion levels. Niclosamide promotes the apoptosis of the tumor cells by influencing Bcl-2 and caspase-3 expression.

Short-term effects of two kinds of plastic mulch on Oncomelania hupensis snail control in irrigation and drainage ditches in Yunnan Province / 中国血吸虫病防治杂志

Objective To evaluate and compare the short-term effects of two kinds of plastic mulch on Oncomelania hupensis snail control in irrigation and drainage ditches with snails in Yunnan Province. Methods The irrigation and drainage ditches with high density of Oncomelania hupensis snails were chosen as the investigation sites,and then 4 groups were set,namely a colorless plastic mulch group,black plastic mulch group,colorless plastic mulch with molluscicide group and black plastic mulch with molluscicide group. The snail situation of the 4 groups was surveyed before the experiment and 7,14,21,30 days after covering plastic mulch,and the snail death rates were compared among the 4 groups. Meanwhile,the hourly temperatures of soil surface,soil surface under plastic mulch and soil layer 5,15 cm under the surface as well as the weather situation during the study period were measured and recorded. Results The average snail mortality rate of the colorless plastic mulch group was only 15.29% that was higher than that of the black plastic mulch group(6.56%)(P 0.05). Both kinds of plastic mulches could raise the temperature of the soil surface under plas-tic mulch and the soil layer below it,and the temperature of soil under the mulches increased over the cover time,and the aver-age temperature of the soil surface under the black mulch in 30 days was higher than that under the colorless mulch. Conclu-sion It is not suitable to use plastic mulch only in irrigation and drainage ditches with snails widely in Yunnan Province be-cause of its low effect,and if necessary,the molluscicide should be added.

Molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt(SC-NE)against Oncomelania hupensis snails in laboratory and field. Methods The experiment of SCNE against the snails by using the immersing and spraying methods was performed in laboratory and field,with control groups of wettable powder of ni-closamide ethanolamine salt(WPN). Results In the laboratory,LC50(s) of SCNE for 24,48 h and 72 h by using the immersion method were 0.0926,0.0629 mg/L and 0.0549 mg/L,respectively. The mortality rates of snails for 24,48 h and 72 h by using the immersion method were all 100％ with the concentrations of 0.25 mg/L. The mortality rates of snails were all 100％ while spraying SCNE for 3 d in the laboratory with the concentrations of 0.25 g/m2. In Jiangling County,except 0.5 g/m3 SCNE immers-ing the snails for 24 h,the mortality rates of snails by using SCNE with the immersing method were all 100％. While the concen-tration of SCNE was 0.5 g/m3 or above,the mortality rates were all 100％after the use of it with the immersion method for 2 d in Gong'an County. In Jiangling County,the mortality rates of snails by using SCNE 0.5 g/m3 for 1 d,3 d,and 7 d with the spray-ing method were 87.5％,92.82％and 97.40％respectively. While the concentration of SCNE was 0.5 g/m3,the mortality rates were 85.94％,86.78％and 94.21％respectively after the use of it with the spraying method for 1 d,3 d,7 d in Gong'an Coun-ty,and the molluscicidal effect of SCNE(1.0 g/m2)was higher than that of WPN. Conclusion SCNE has a high molluscicidal effect in the laboratory and field,and it is a novel and simple formulation of niclosamide.