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

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)

Himenolepiasis por Hymenolepis nana, a propósito de 2 casos / Hymenolepiasis due to Hymenolepis nana, in relation to 2 cases

La himenolepiasis es una infección parasitaria cosmopolita; su prevalencia global oscila entre 0.1 y 58%, es más frecuente en niños. El agente etiológico es el cestodo Hymenolepis nana, que evoluciona mediante ciclos vitales: monoxénico (en el cual existe un único huésped definitivo e intermediario que puede ser el ser humano, ratas y ratones) y un ciclo heteroxénico (en el que un artrópodo ­pulga o gorgojo­ consume los huevos presentes en las materias fecales y desarrolla el cisticercoide ­larva­). Este vector es ingerido por el huésped definitivo (humano o rata) desarrollando posteriormente la infección. Los síntomas dependerán del grado de afectación de las vellosidades del intestino delgado; se destacan: dolor abdominal, meteorismo, diarrea, irritabilidad, prurito anal y anorexia. El tratamiento de elección es el praziquantel 25 mg/kg dosis única. Presentamos 2 casos de usuarios adultos que acuden al Centro de Salud de San Antonio de Pichincha ­ Quito, con sintomatología inespecífica, a los que se les realiza examen coproparasitario como control al primero y como sospecha por contacto con roedor al segundo; en ambos casos se encuentra el parásito. Aunque se decide iniciar el tratamiento con praziquantel, no se lo consigue, por lo que se prescribe niclosamida 2 g por día durante 2 días; desapareció el cuadro sintomático y el parásito en el examen de control de laboratorio (AU)

Hymenolepiasis is a parasitic infection with a cosmopolitan distribution, it has a global prevalence ranging from 0.1 to 58%. Is more frequent in children and is produced by the Hymenolepis nana basket, which evolves through life cycles: monoxenic, with a single final host and an intermediate host, which can be a man, rats or mice. In the heterocyclic cycle, it's evident the presence of an arthropod (flea or weevil) that consumes eggs in fecal matter and develops the cysticercoid (larva). Then, this vector is ingested by the definitive host (human or rat) who is going to develop the infection subsequently. Symptoms depend on the degree of involvement of villi in the small intestine, including abdominal pain, bloating, diarrhea, irritability, anal pruritus and anorexia. The treatment of choice is praziquantel in a single dose of 25 mg. In the present work, we describe the cases of users who visited the Health Center of San Antonio de Pichincha in Quito. They came with nonspecific symptomatology. At first, they were analyzed through a coproparasitary examination of the control and the suspicion of contact with the rodent at second. In both cases with the pathology. It was decided to start the treatment. However, this medication was not obtained, so a dose of 2 g per day for 2 days of niclosamide was given for disappearing of the clinical picture. (AU)

In-vitro evaluation of antihelminthic activity of Allium sativum against adult Cotylophoron cotylophorum [Paramphistomidae]

Plant-based anti-helminthics have been reported for their safety and eco-friendly properties. They are used as alternatives for toxic chemical drugs. Allium sativum [garlic] has shown antihelminthic action in vitro and in vivo against many helminthes. The present study was designed to evaluate the in vitro antihelminthic activity of A. sativum in comparison with two commonly used antihelminthic drugs; albendazole and niclosamide against the cattle amphistome, Cotylophoron cotylophorum. Live adult C. cotylophorum worms were collected from the rumen and reticulum of slaughtered cattle. Twelve media [natural calf serum, RPMI 1640 in ten formulas and normal saline] were evaluated to choose the most favorable one for incubation of worms during the study. Different concentrations of albendazole, niclosamide and alcoholic extract of A. sativum were tested in vitro against C. cotylophorum. Treated worms were examined after 2, 4, 8, 12 and 24 hours and the mortality rate was calculated in all experiments. The effect of the sub-lethal concentrations of albendazole and A. sativum on the tegument of the worm was evaluated by scanning electron microscopy [SEM]. Albendazole was highly effective against adult C. cotylophorum, where it exhibited dose-dependent lethal activity at different concentrations. Niclosamide was less effective, with high mortality rates recorded at relatively higher concentrations than albendazole. SEM revealed remarkable changes in the tegument and muscles of adult C. cotylophorum treated with a sub-lethal concentration of albendazole [1.5 mg/L] for eight hours. The whole tegument was deformed and papillae were hardly seen as swollen bodies. Numerous blebs and crater-like structures covered the whole tegument. A. sativum alcoholic extract gave high mortality rate at a relatively low concentration. SEM of adult worms treated with a sub-lethal concentration of A. sativum alcoholic extract [1.0 mg/L] revealed moderate changes in the tegument and a more severe effect on the muscle integrity. The mouth appeared flaccid and slightly retracted and the tegument surrounding it appeared feebly damaged and corrugated. The papillae lost their uniform structure. The acetabulum appeared retracted and lost its specific shape. The present study revealed that A. sativum alcoholic extract has an antihelminthic effect against adult C. cotylophorum at low concentrations. Garlic-based antihelminthic product may be used against rumen cattle amphistomes as an alternative for the commonly used chemical drugs

Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells / 癌症

Niclosamide, an oral antihelminthic drug, has been used to treat tapeworm infection for about 50 years. Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs. Recently, several groups have independently discovered that niclosamide is also active against cancer cells, but its precise mechanism of antitumor action is not fully understood. Evidence supports that niclosamide targets multiple signaling pathways (NF-κB, Wnt/β-catenin, Notch, ROS, mTORC1, and Stat3), most of which are closely involved with cancer stem cells. The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed. A method for synthesizing a phosphate pro-drug of niclosamide is provided. Given its potential antitumor activity, clinical trials for niclosamide and its derivatives are warranted for cancer treatment.

Human infection with bertiella studeri [cestode: anoplocephalidae] in an Egyptian worker returning back from Saudi Arabia

Perhaps this is the first case of bertiellosjs studeri record in Egyptian worker returning back from Saudi Arabia. The patient was resistant to Niclosamide but successfully treated with Commiphora molmol extract

Bioensaio de atividade moluscicida adaptado para a avaliação de extratos de plantas medicinais / Bioensayo de actividad moluscicida adaptado para evaluación de extractos de plantas medicinales / Bioassay of molluscicidal activity adapted for the evaluation of medicinal plant extracts

Nesta nota é apresentada detalhadamente a metodologia (preparação dos extratos, adaptação dos caramujos, ensaio de atividade, destino dos caramujos) usada para a avaliação da atividade moluscicida de extratos de plantas frente a caramujos da espécie Biomphalaria glabrata. A adaptação desta metodologia tem o propósito de avaliar extratos naturais para a busca de produtos alternativos mais baratos, biodegradáveis, seguros e disponíveis localmente, para o controle das populações de caramujos.

The methodology (extract preparation, adaptation of the snails, activity test, destiny of the snails) used for the evaluation of the molluscicidal activity of plant extracts in relation to snails from the Biomphalaria glabrata species appears in detail in this note. The adaptation of this methodology has the purpose of evaluating natural extracts in order to find cheaper, biodegradable, safe and easily available alternative products for the control of the populations of snails.

En este apunte se presenta detalladamente la metodología (preparación de los extractos, adaptación de los caracoles, ensayo de actividad, destino de los caracoles) utilizada para la evaluación de la actividad moluscicida de extractos de plantas frente a caracoles de la especie Biomphalaria glabrata. La adaptación de esta metodología tiene el propósito de evaluar extractos naturales para la búsqueda de productos alternativos más baratos, biodegradables, seguros y disponibles localmente, para el control de las poblaciones de caracoles.

Laboratory evaluation of a new molluscicide application method

The paper reports an investigation, in the laboratory, of a new method for the application of the molluscicide, Niclosamide, using the concept of slow-release with local materials as matrices. The local matrices tested were the seeds of the mango and the cobs of the maize. The objective was to reduce the cost of the snail control operations. 1, 5 and 10 seeds and/or cobs were immersed into 4 concentrations [0.6, 1.0, 2.0 and 4.0 ppm] of Niclosamide for different hours [1, 2, 6, 12, 24 and 48 hrs]. B. pfeifferi snails were then exposed to the immersed seeds and cobs for different hours [1, 2, 6, 24, 48 and 72 hours]. Different statistical procedures were used to analyze the data. The mean time of mortality of B. pfeifferi snail indicated that the cobs of the maize were a superior matrix for Niclosamide than the seeds of the mango. The LC[50] and LC[95] indicated that the combination of 10 cobs immersed for 12 hours in 4.0 ppm was the effective combination to achieve high mortality rates among B. pflefferi snails after 48 hours exposure. The method proved to be, in the laboratory, cost-effective in terms of the quantity of Niclosamide required to result in a high mortality among the snails

Efficacy of temperature, and two commonly used molluscicides and fertilizers on fasciola gigantica eggs

This study .evaluated the effect of temperature, molluscicides [Copper sulphate and Niclosamide], fertilizers [Superphosphate and Ammonium sulphate] on the hatchability of Fasciola gigantica eggs. The results showed that hatchability decreased to 4% when eggs were incubated in bile secretion at 37°C for 5 days and to 1.4% for 10 days, but few eggs incubated in water at 37°C hatched. Bile secretion at 37°C was a poor medium for in-vitro egg preservation. But, hatching occurred only when eggs were transferred to water at 26°C. Temperature fluctuation from 26-4°C or from 32- 4°C had an inhibitory effect on embryos development [35.2% and 32.3%, respectively] as compared to controls [60% and 63.9%, respectively]. The incubation period [19 and 17 days] was higher than controls [14 and 12 days, respectively]. The LC50 and LC9o of Copper sulphate and Niclosamide against Biomphalaria alexandrina and Lymnaea natalenesis had no toxic effect on Fasciola eggs. The higher concentrations of Copper sulphate [30ppm] and Niclosamide [Ippm] slightly lower eggs hatchability rate than controls. The rate decreased by increasing the exposure time from 3 to 6 hours with both molluscicides. Ammonium sulphate had a lethal effect on eggs, but Superphosphate had some inhibitory effect on egg development, which increased by increasing Superphosphate concentration or with the prolongation of the exposure time

Correlation between ovicidal effectiveness and egg-membrane penetration determined by chromatography in two modes of biomphalaria Alexandrina eggs exposure to certain plant and chemical molluscicides

The weak ovicidal effect of the plants having molluscicidal activity is a criterion against their field application in controlling the medically important snails. Chemical molluscicides are potent against snails and their eggs. This work is a trail to use bayluscide and CuSO4 [chemical molluscicides] in sub lethal concentrations to improve the ovicidal effect of Anagallis arvensis and Calendula micrantha plants against the eggs of Biomphalaria alexandrina snails through two modes of eggs exposure. The first was the pre-exposure of snail's eggs to sub lethal concentrations of chemical molluscicides followed by plant exposure and this improve the effect of plants against the snail's eggs with a synergistic ratio ranged from 1.5 to 4.49. While the second mode of exposure is to evaluate the toxicity of mixtures of chemical molluscicides and plants against snail's eggs. It was noticed that this moda resulted in 100% mortality when eggs exposed to mixture of LC15 of C. micrantha or LC25 of A. arvensis with sublethal concentrations of the molluscicides bayluscide or copper sulphate. TLC reveals that the number of the penetrated plant compounds increased in all copper sulphate treatments and in pre-exposure of C. micrantha by bayluscide while the same number of plant compounds were penetrated in the rest of bayluscide treatments as in the cese of the plant alone. So, the increase in plant potency was through chemicals that affect the eggs' membrane to be permeable for more active ingredients [more in number or concentration or both of them] of the tested plants to become in contact with the target embryos

Snail control by using soil pasting mixed with niclosamide / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of snail control through soil pasting mixed with niclosamide.</p><p><b>METHODS</b>Four sites were selected in different epidemic areas in Sichuan province. Soil pasting mixed with niclosamide was carried on, and the dosage was 0 g/m2, 4 g/m2, 6 g/m2, 8 g/m2 and 10 g/m2 respectively. The mortality rate of snail and the density of snail were observed after 7, 15, 30, 90 and 180 days.</p><p><b>RESULTS</b>The mortality rate of snail was more than 43.3% in blank group after 30 days. The mortality rate of snail was from 75.3% to 100.0% at 4 g/m2 group after 30 days. The mortality rate of snail in 4 g/m2 group was significantly higher than that in the blank group (chi2 = 31.27, P < 0.05). There was no significant difference in the mortality rate of snail among all study groups (chi2 = 1.07, P > 0.05). The decrease rate of snail density was more than 90%. The mortality rate of snail was about 30% higher in Chantu group than Qutu group. The unit cost of Pasting-Mixing Drug with Soil was from 5 to 7 times of spray method, but the total cost was similar for the. two methods at the endpoint of the snail control.</p><p><b>CONCLUSION</b>The effect of soil pasting mixed with niclosamide is good, and the dosage of 4-6 g/m2 is suggested in snail control.</p>

Field trials of low dose Bayluscide on snail hosts of schistosome and selected non-target organisms in sahelian Cameroon

More than 85 percent of all cases of schistosomiasis in Cameroon occur in the northern sahelian half of the country representing 20 percent of the population. Several workers have advocated the integrated approach to schistosomiasis control, including snail control, but the death and decay of aquatic organisms, and fish kill that often follows Bayluscide application at the dose of 1g/m³ decrease its acceptability. The present study was designed to assess the effect of lower Bayluscide doses on snail host and non-target fish, frog, the tadpole kill. Bayluscide was applied to study ponds at concentrations of 0, 0.25, 0.5, and 1 g/m³ (ppm). Pre and post application assessment of snails hosts of schistosomes, fish, frog, and tadpole kill were carried out. All 0.25, 0.5, and 1 g/m³ Bayluscide concentrations reduced snail population significantly. Bayluscide concentration of 0.50 g/m³ applied in two rounds of 0.25 g/m³ resulted in high snail mortality and low lethality to fish, frogs, and tadpoles. Further studies are needed to assess the cost-effectiveness of Bayluscide in the control of schistosomiasis following the simplified approach.

[Cleaning and molluscicide treatment for schistosomiasis control]

We evaluated the effect of niclosamide treatment and the additional cleaning of basins and pools on the density and infection rate of Bulinus truncatus within the irrigation network of Oudaya. The period prior to molluscicide treatment [January-May] revealed a mean density of 151 snails/m2 in 1995-96 and 127 snails/m2 in 1997-98. After cleaning had started, the mean density prior to molluscicide treatment fell to 84 snails/m2 in 1999-2000. After molluscicide treatment, densities dropped to very low levels only rising again from October. In November 1999-96 mean density reached 150 snails/m2 but after cleaning started in 1997-98 this only reached 80 snails/m2; in 1999-2000, when cleaning was undertaken 3 months before and after molluscicide treatment, it reached only 18 snails/m2. From 1995 to 1996, the infection rate rose slightly [4.54% to 5.44%], but, from 1997, there was a significant drop [3.13% to 2.16%]

A study on the effect of Oncomelania hupensis hupensiss killed with niclosamide in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the effect of Oncomelania hupensis hupensis of niclosamide, and exploring the main influencing factors.</p><p><b>METHODS</b>The samples of Oncomelania hupensis hupensis were collected from 37 sampling sites in 33 counties of 10 provinces by means of stratified random sampling methods in accordance with the categories of Oncomelania hupensis hupensis habitats. Samples were randomly located into study group and control group. Oncomelania hupensis hupensis of the study group was marinated in different concentration liquor of niclosamide which was confected with water for 24 hours or 48 hours, then LC50 of niclosamide by which Oncomelania hupensis hupensis was killed and amount calculated. The influencing factors of the mortality of Oncomelania hupensis hupensis in the study group was statistically analyzed by 2 test and by multiple logistic regression using SPSS 13.0 statistical software.</p><p><b>RESULTS</b>The mortality of Oncomelania hupensis hupensis of the two test groups which were marinated in 0.5 mg/L liquor for 48 hours and 1.0 mg/L liquor for 24 hours was 100%. The effect of Oncomelania hupensis hupensis killed by niclosamide was markedly reduced along with the reduction of drug concentration. The average LC50 rates of niclosamide liquor by which Oncomelania hupensis hupensis killed for the 24 hours and 48 hours in the study group, were 0.0939 mg/L and 0.0625 mg/L, respectively. There was significant difference between the two test groups (chi(2) = 5.001, P <0.01) . In determinate range of concentration, the mortality of Oncomelania hupensis hupensis showed significant difference among the geographic types of habitat ( chi(2) = 4.264, P < 0.05). By means of multiple logistic regression using SPSS 13.0 statistical software, the estimate value of coefficient of regression on the influence factors, drug concentration, test time and the geographic types of habitat were 2. 047 ( OR = 5. 573), 0.263 ( OR = 2.924) and 0. 187- 0.210 ( OR = 1.969- 2. 560), respectively.</p><p><b>CONCLUSION</b>Niclosamide could kill Oncomelania hupensis hupensis effectively. The main influencing factors on the efficacy of niclosamide by which Oncomelania hupensis hupensis was killed, appeared to be drug concentration, time of testing and the geographic types of habitat.</p>

Synergic effects of synthesis arecoline in combination with snail-killing drugs niclosamide / 中华预防医学杂志

<p><b>OBJECTIVE</b>To prove that synthetic Are combination with snail-killing drug Nic can increase the effects of snail-killing remarkably.</p><p><b>METHODS</b>In indoor immersing experimentation, the experiments were divided into 4 groups, 30 snails in each group, to observe the rate of opening operculum, the rate of climbing adhesion and the rate of death at 3, 6 and 24 hours respectively. In field experimentation, we intermixed 0.1 mg/L Are with 0.2 mg/L Nic as sample as contrasted with 2 mg/L Nic and non-drug group. Immersing method (we chose three slots each size were 10 m x 2 m x 1 m.) and insufflation method (we chose three patch of bottomlands each area were 10 m x 5 m.) were used to kill snails separately and the death rate of fish, at the same time was observed.</p><p><b>RESULTS</b>In the room, as we added 0.1 mg/L Are to the solution of 0.1 mg/L and 0.2 mg/L Nic separately, the opening operculum rate for 6 hours was increased from 20% and 12% to 100% and 95%, the climbing adhesion rate for 6 hours decreased from 17% and 53% to 3% and 5%, the death rate for 24 hours increased from 25% and 40% to 90% and 100%. In the field, the snails death rate in sample group and in contrastive group applied with immersing method and insufflation method for 72 hours were 95.9%, 93.3% and 100%, 95.8%; only one small fish (2 cm long) died in sample group, and all fishes died in Nic group, and all fish were alive in non-drug group.</p><p><b>CONCLUSION</b>It proved that synthetic Are combination with snail-killing drug Nic might decrease Nic dosage and toxicity and increase the effects of snail-killing.</p>

Effect of synthesized niclosamide organophosphortus derivatives on some metabolic aspects of Biomphalaria alexandrina snails and its compatibility to Schistosoma mansoni

The Molluscicidal potency of four synthesized Mannich bases and ten organophosphorus derivatives of bayluscide [niclosamide] were determined. Using Biomphalaria alexandrina snail, the intermediate host to Schistosoma mansoni in Egypt, of these derivatives,a single Mannich bases derivative [compound No, 13] showed higher molluscicidal effect than niclosamide, LC[50] 0.4 ppm after 24 hours at 25°C compared with 0.5 ppm for niclosamide. Three other derivatives [No. 15, 12 and 8] showed slightly less effect, their LC[50] 1.9, 3.4 and 4.1 ppm, respectively, Meanwhile, the four compounds showed considerable reducting effect on the cercarial production of schistosome-infected snails previously exposed to LC[5] of each compound before miracidial infection. Thus, the mean periodic number of cercariae/snail [two hours weekly] was found to be 55.8 +/- 41.8, 95.9 +/- 78.9, 162.6 +/- 145 and 209.35 +/- 168.4 cercariae/snail, respectively versus 242 +/- 230.4 and 502 +/- 290.4 in the case of niclosamide-treated and non-treated snails. The effect of the four compounds was tested on the glycolytic enzymes of snails, namely, hexolinase [HK], pyruvate kinase [PK] and glucose phosphate isomerase [GPI]. Much more reduction was recognized in [HK] by compounds No. 8 and 13 in comparison, with niclosamide and nontreated snails, being 2.6 +/- 0.82 and 3.7 +/- 1.6 n moles/min/g tissue versus 3.9 +/- 0.58 and 9.8 +/- 2.7 n moles/min/g tissue in niclosamide-treated and non-treated groups, respectively. PK showed also higher reduction with four compounds namely 15, 13, 12 and 8 compared with niclosamide-treated and non-treated snails, being 0.3 +/- 0.1, 0-.39 +/- 0.29, 0.46 +/- 0.08 and 0.98 +/- 0.138 in comparison with 1.51 +/- 0.52 and 1.8 +/- 0.62, respectively. No considerable change was found in the level of GPI in snails treated with 15, 13, 12 and 8 compounds relative to niclosamide-tested snails. The present results show that reduction in the periodic cercarial production is correlated with the lower level of HK enzyme in treated snails

Impact of certain plants and synthetic molluscicides on some fresh water snails and fish

The LC50 [78, 85 ppm] and LC90 [88, 135 ppm] of Anagalis arvensis and calendula micrantha respectively against Biomphalaria alexandrina were higher than those of the non-target snails, Physa acuta, Planorbis planorbis, Helisorna duryi and Melanoides tuberculata. In contrast, the LC50 of Niclosamide [0.11 ppm] and Copper sulphate [CuSo4] [0.42 ppm] against B. alexandrma were lower than those of the non-target snails. The mortalities percentage among non-target snails ranged between 0.0 and 20% when sublethal concentrations of CuSo4 against B. alexandrina mixed with those of C. micrantha and between 0.0 and 40% when mixed with A. arvensis. Mortalities ranged between 0.0 and 50% when Niclosamide was mixed with each of A. arvensis and C. micrantha. A. arvensis induced 100% mortality on Oreochromis niloticus after 48 hrs exposure and after 24 hrs for Gambusia affinis. C. micrantha was non-toxic to the fish. The survival rate of O. niloticus and G. affinis after 48 hrs exposure to 0.11 ppm of Niclosamide were 83.3% and 100% respectively. These rates were 91.7% and 93.3% respectively when each of the two fish species was exposed to 0.42 ppm of CuSo4. Mixture of sub-lethal concentrations of A. arvensis against B. alexandrina and those of Niclosamide or CuSo4 at ratios 10:40 and 25:25 induced 66.6% mortalities on O. niloticus and 83.3% at 40: 10. These mixtures caused 100% mortalities on G. affinis at all ratios. A. arvensis CuSo4 mixtures at 10:40 induced 83.3% and 40% mortalities on O. niloticus and G. affinis respectively and 100% mortalities on both fish species at ratios 25:25 and 40:10. A mixture of sub-lethal concentrations of C. micrantha against B. alexandrina and of Niclosamide or CuSo4 caused mortalities of O. niloticus between 0.0 and 33.3% and between 5% and 35% of G. affinis. The residue of Cu in O. niloticus were 4.69, 19.06 and 25.37 mg/ l kgm fish after 24, 48 and 72 hrs exposure to LC0 of CuSO4 against B. alexandrina respectively

Study on human taeniasis by administering anti-taenia drug

Mazandaran province, northern Iran, has been an area with highest prevalence of infectivity with human taeniasis during past decades. In order to assess current situation of taeniasis in the province by a method which can yield a correct estimation of infection rate, this study was performed by administrating anti-Taenia drug, during 2003-2004. A total of 417 people were randomly selected from rural areas of Mazandaran province. All of them were at first given a dose of niclosamide [2-4 500 mg tablets] and bisacodile [1-3 5 mg tablets]; then their 36 h stool passage was collected and examined macroscopically and microscopically. The results revealed that 2 individuals [0.5%] were infected with Taenia saginata. Compared with previous decades, there is a sharp drop on human taeniasis in the study area. Infected peoples were followed up till complete treatment

Molluscicidal effect of nicotinanilide and its intermediate compounds against a freshwater snail Lymnaea luteola, the vector of animal schistosomiasis

The molluscicidal effect of nicotinanilide was evaluated and compared with niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature, young mature, and adults. Calculated values of lethal concentrations (LC50 and LC90 ) showed that both nicotinanilide and niclosamide as toxic against eggs, immature, and adults. The young mature stage of the snails was comparatively more tolerant to both molluscicides than the other stages. The toxicity of the intermediate compounds of nicotinanilide against the young mature stage of the snails showed them as ineffective. The mortality pattern of the snails exposed to LC90 concentration of these molluscicides showed niclosamide to kill faster (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies it may be concluded that both molluscicides are toxic against all the stages of the L. luteola snails.