Death Of Worms Research Articles

Participation of Acyl-Coenzyme A Synthetase FadD4 of Pseudomonas aeruginosa PAO1 in Acyclic Terpene/Fatty Acid Assimilation and Virulence by Lipid A Modification.

The pathogenic bacterium Pseudomonas aeruginosa possesses high metabolic versatility, with its effectiveness to cause infections likely due to its well-regulated genetic content. P. aeruginosa PAO1 has at least six fadD paralogous genes, which have been implicated in fatty acid (FA) degradation and pathogenicity. In this study, we used mutagenesis and a functional approach in P. aeruginosa PAO1 to determine the roles of the fadD4 gene in acyclic terpene (AT) and FA assimilation and on pathogenicity. The results indicate that fadD4 encodes a terpenoyl-CoA synthetase utilized for AT and FA assimilation. Additionally, mutations in fadD paralogs led to the modification of the quorum-sensing las/rhl systems, as well as the content of virulence factors pyocyanin, biofilm, rhamnolipids, lipopolysaccharides (LPS), and polyhydroxyalkanoates. In a Caenorhabditis elegans in vivo pathogenicity model, culture supernatants from the 24-h-grown fadD4 single mutant increased lethality compared to the PAO1 wild-type (WT) strain; however, the double mutants fadD1/fadD2, fadD1/fadD4, and fadD2/fadD4 and single mutant fadD2 increased worm survival. A correlation analysis indicated an interaction between worm death by the PAO1 strain, the fadD4 mutation, and the virulence factor LPS. Fatty acid methyl ester (FAME) analysis of LPS revealed that a proportion of the LPS and FA on lipid A were modified by the fadD4 mutation, suggesting that FadD4 is also involved in the synthesis/degradation and modification of the lipid A component of LPS. LPS isolated from the fadD4 mutant and double mutants fadD1/fadD4 and fadD2/fadD4 showed a differential behavior to induce an increase in body temperature in rats injected with LPS compared to the WT strain or from the fadD1 and fadD2 mutants. In agreement, LPS isolated from the fadD4 mutant and double mutants fadD1/fadD2 and fadD2/fadD4 increased the induction of IL-8 in rat sera, but IL1-β cytokine levels decreased in the double mutants fadD1/fadD2 and fadD1/fadD4. The results indicate that the fadD genes are implicated in the degree of pathogenicity of P. aeruginosa PAO1 induced by LPS-lipid A, suggesting that FadD4 contributes to the removal of acyl-linked FA from LPS, rendering modification in its immunogenic response associated to Toll-like receptor TLR4. The genetic redundancy of fadD is important for bacterial adaptability and pathogenicity over the host.

Synthetic Aurones: New Features for Schistosoma mansoni Therapy.

In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones (1) and (2) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones (1) and (2) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds (1) and (2), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis.

Test the Activity of the Juice and Infusion of Rumput Kebar (Biophytum petersianum Klotzsch) againts Ascaridia galli worms in Vitro

Kebar grass contains active compounds that can be used as herbal ingredients in the treatment of diseases. This study was conducted to test the anthelmintic activity of grass kebar against worms Ascaridia galli in vitro. This study uses Kebar grass juice and infusion with a concentration of 15%, 30%, 45%, and 60%, and 4 repetitions. Each level of the experiment is placed in each cup containing 25 ml of solution and 5 worms. Worm mortality is recorded every 2 hours. The results showed that the juice and infusion of kebar grass were concentrations of 15%, 30%, 45%, 60% capable of killing worms with a mean time on the juice of Kebar grass respectively 9.5; 8; 7.5; 7 hours, and the average time for Kebar grass infusion is 9.5; 8.5; 8; 7.5 hours. The immersion time is a good variable to explain the variable of worm death at each concentration of treatment. There is an anthelmintic effect on grass juice and infuse kebar grass against worms Ascaridia galli in vitro. The duration of soaking and the concentration of juice and infusion of Kebar grass in this study had a significant effect on the mortality of worms. It was concluded that the juice and grass infuse kebar(Biophytum Petersianum Klotzsch) have anthelmintic effect against worms Ascaridia galli in vitro. Concentration Kebar grass juice and infuse kebar is increasing, then the shorter the time it takes to kill the worms Ascaridia galli in vitro.

Brugia malayi Glycoproteins Detected by the Filariasis Test Strip Antibody AD12.1.

Rapid and accurate prevalence mapping of lymphatic filariasis (LF) is necessary to eliminate this disfiguring and disabling neglected tropical disease. Unfortunately, rapid tests such as the filariasis test strip (FTS) for Wuchereria bancrofti, the causative agent of LF in Africa, can cross-react with antigens circulating in some persons infected by the African eye worm, Loa loa, rendering the test unreliable in eleven co-endemic nations. The intended target of the FTS is a heavily glycosylated W. bancrofti circulating filarial antigen (Wb-CFA). Previously, we determined that the FTS monoclonal antibody, AD12.1, which detects a carbohydrate epitope on Wb-CFA, also detects multiple L. loa proteins in cross-reactive sera from persons with loiasis. Since the carbohydrate epitope recognized by AD12.1 is present on glycoproteins of other parasitic nematodes, including Brugia species, it is unclear why reactive glycoproteins are not detected in infections with other filarial parasites. To gain a better understanding of the proteins recognized by the FTS diagnostic antibody, we used proteomics and lectin array technology to characterize filarial glycoproteins that are bound by the AD12.1 antibody using Brugia malayi as a model. Distinct but overlapping sets of AD12 glycoproteins were identified from somatic and excretory/secretory worm products. One of the identified proteins, Bm18019 was confirmed as a secreted AD12-reactive glycoprotein by in-gel proteomics and immunoassays. Based on lectin binding patterns, Brugia AD12-reactive glycoproteins express glycans including core fucose, galactose, N-acetylglucosamine and galactose (β1-3)N-acetylgalactosamine in addition to the epitope recognized by AD12.1. None of the lectins that bound B. malayi AD12 glycoproteins had affinity for the Wb-CFA, highlighting a key difference between it and other AD12 glycoproteins. B. malayi somatic and excretory/secretory proteins are similar to L. loa antigens found in FTS-positive human sera, bolstering the hypothesis that circulating L. loa AD12 antigens result from worm tissue damage or death. The difference in glycan and protein composition between the Wb-CFA and other AD12 glycoproteins can be used to differentiate LF from cross-reactive loiasis.

Anti-trypanosomal and anthelminthic properties of ethanol and aqueous extracts of Tetrapleura tetraptera Taub

Trypanosomosis and helminthosis, considered as part of neglected tropical diseases, are parasitic infections of public health importance, especially in Africa. Medicinal plants have been used in most parts of Africa, to treat these parasitic infections. The study aims to determine the anti-trypanosomal and anthelminthic properties of Tetrapleura tetraptera (fruit and stembark). The aqueous extracts of T. tetraptera fruit (TTFaq) and stembark (TTSaq), as well as ethanol extracts of T. tetraptera fruit (TTFe) and stembark (TTSe), were screened for their in vitro anti-trypanosomal and anthelminthic activities against T. b. brucei and Pheretima posthuma worms, respectively. Preliminary phytochemical screening of all extracts and gas chromatography-mass spectrometry (GC–MS) analysis of most active extracts were conducted. TTFaq exhibited anti-trypanosomal activity with IC50 of 18.18 μg/mL. TTSe and TTFe had moderate anti-trypanosomal activity with IC50 of 34.76 and 34.84 μg/mL, respectively. TTSaq had relatively low activity against the parasite with IC50 of 55.03 μg/mL. The SI of T. tetraptera extracts was between the range of 0.14–2.09. TTFaq showed dose-dependent activity causing paralysis and death of the adult worms at all concentrations. At the least concentration of 0.625 mg/mL, TTFaq induced paralysis and death after 101.88 ± 0.8 and 242.64 ± 0.38 min of exposure, respectively compared with the negative control (p < 0.0001). TTFe, TTSe and TTSaq caused paralysis of worms after 318.32 ± 0.74, 422.5 ± 0.72, 422.20 ± 0.55 min of exposure at minimum concentrations of 2.5, 10 and 5 mg/mL, respectively (p < 0.0001). However, no death was observed in worms treated with TTFe, TTSe and TTSaq at all test concentrations. In the presence of sub-minimal inhibitory concentration of the extracts, TTFaq potentiated the anthelminthic activity of albendazole whiles TTFe, TTSaq and TTSe inhibited the activity of albendazole. Phytochemical screening revealed the presence of saponins, triterpenoids, reducing sugars, flavonoids (absent in TTFe), steroids (absent in TTFaq) and tannins (absent in TTSe and TTFe) in the extracts. GC–MS revealed the presence of 9-octadecenamide and betulic acid in TTFaq. Hence, there was evidence provided here that Tetrapleura tetraptera may be effective. This gives credence to their folkloric use. However, further study might be necessary to ascertain safety use in both humans and animals.

Schistosoma mansoni alter transcription of immunomodulatory gene products following in vivo praziquantel exposure

Control of the neglected tropical disease schistosomiasis relies almost entirely on praziquantel (PZQ) monotherapy. How PZQ clears parasite infections remains poorly understood. Many studies have examined the effects of PZQ on worms cultured in vitro, observing outcomes such as muscle contraction. However, conditions worms are exposed to in vivo may vary considerably from in vitro experiments given the short half-life of PZQ and the importance of host immune system engagement for drug efficacy in animal models. Here, we investigated the effects of in vivo PZQ exposure on Schistosoma mansoni. Measurement of pro-apoptotic caspase activation revealed that worm death occurs only after parasites shift from the mesenteric vasculature to the liver, peaking 24 hours after drug treatment. This indicates that PZQ is not directly schistocidal, since PZQ’s half-life is ~2 hours in humans and ~30 minutes in mice, and focuses attention on parasite interactions with the host immune system following the shift of worms to the liver. RNA-Seq of worms harvested from mouse livers following sub-lethal PZQ treatment revealed drug-evoked changes in the expression of putative immunomodulatory and anticoagulant gene products. Several of these gene products localized to the schistosome esophagus and may be secreted into the host circulation. These include several Kunitz-type protease inhibitors, which are also found in the secretomes of other blood feeding animals. These transcriptional changes may reflect mechanisms of parasite immune-evasion in response to chemotherapy, given the role of complement-mediated attack and the host innate/humoral immune response in parasite elimination. One of these isoforms, SmKI-1, has been shown to exhibit immunomodulatory and anti-coagulant properties. These data provide insight into the effect of in vivo PZQ exposure on S. mansoni, and the transcriptional response of parasites to the stress of chemotherapy.

In vitro anthelmintic activities of shrub plants extracts for Haemonchus contortus worms

This study was conducted to evaluate the anthelmintic activity and effectiveness of shrubs as forage containing tannins as anti-parasites in the digestive tract of small ruminants by in vitro. The types of shrubs used in the study included anting-anting (Acalypha australis linn), bandotan (Ageratum conyzoides), som jawa (Talinum paniculatum), suruhan (Peperomia pellucid L.), and tapak liman (Elephantopus scaber). This study at P0: aquadest (negative control) P1: 10% concentration level of shrubs; P2: 20% concentration level of shrubs, and P3: albendazole 100% (positive control) after 60 minutes of time. The methods of Haemonchus contortus adult worm mortality test were used to investigate the inhibiting effect of in vitro worm mortality from shrub plant extracts. The results of this study on in vitro screening of adult worms, at an increasing concentration, the number of worms that died was significantly more (P <0.05). The highest worm mortality was seen at the concentration level of tapak liman leaf extract (Elephantopus scaber) as much as 20% with a tannin content of 8.89% so that the anthelmintic potential was seen in adult worm mortality. From this study, it can be concluded that the extract of shrubs shows significant anthelmintic activity against the death of adult female Haemonchus contortus worms so that it has the potential to play a role in parasite control in the digestive tract of small ruminants.

Enolase2 and enolase1 cooperate against neuronal injury in stroke model

Stroke is one of the leading causes of death in adults worldwide. However, the mechanism causing neuronal death remains poorly understood. Our previous report showed that enolase1 (ENO1), a key glycolytic enzyme, alleviates cerebral ischemia-induced neuronal injury. It remained unclear whether enolase2 (ENO2) affects neuronal injury in stroke models. Here, we examined the effects of ENO2 in several stroke models. The results showed that the expression level of ENO2 was downregulated after 3 h of cerebral ischemia by middle cerebral artery occlusion (MCAO) in the mouse model. ENO2 was expressed in mouse brain and cultured hippocampus neurons. Overexpression of ENO2 in cultured hippocampus neurons did not affect neuronal injury in our oxygen-glucose deprivation (OGD) model. Interestingly, double knock-down (KD) of ENO1 and ENO2 increased neuronal injury while either KD of ENO1 or ENO2 failed to increase neuronal injury in OGD. Deletion of ENO1 did not affect anoxia-starvation (AS)-induced worm death in C. elegans. These findings demonstrated that ENO2 and ENO1 work together against neuronal injury in these stroke models.

Anthelmintic Activities of Polypodium Decumanum Leaf-Extracts

Various herbal plants used in traditional medicines contain a vast array of substances that can be used to treat various disease and complications, the present study deals with anthelmintic activity of different extracts of leaves of Polypodium decumanum, a potential medicinal plant. The crude plant extracts of leaf part exhibited anthelmintic activity. Two concentrations (30mg/ml and 40mg/ml) of each extract were studied, which involved for the determination of time of paralysis and time of death of the test worms. It was found that ethyl acetate extracts exhibited significant anthelmintic activity followed by ethanolic extract and aqueous extract in causing paralysis and death of earth worms.

Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development.

Schistosomiasis is a neglected tropical disease inflicting significant morbidity in humans worldwide. The disease is caused by infections with a parasitic trematode belonging to the genus Schistosoma. Over 250 million people are currently infected globally, with an estimated disability-adjusted life-years of 1.9 million attributed to the disease. Current understanding, based on several immunological studies using experimental and human models of schistosomiasis, reveals that complex immune mechanisms play off each other in the acquisition of immune resistance to infection/reinfection. Nevertheless, the precise characteristics of these responses, the specific antigens against which they are elicited, and how these responses are intricately regulated are still being investigated. What is apparent is that immunity to schistosome infections develops slowly and over a prolonged period of time, augmented by the death of adult worms occurring naturally or by praziquantel therapy. In this review, aspects of immunity to schistosomiasis, host–parasite interactions and their impact on schistosomiasis vaccine development are discussed.

EVALUATION OF ANTHELMINTIC ACTIVITY OF BAUHINIA VARIEGATA LINN METHANOLIC ROOT EXTRACT ON PHERETIMA POSTHUMA

Methanolic extracts from roots of Bauhinia variegata linn were investigated for their anthelmintic activity by using three concentrations (10, 25, &amp; 50mg/ml) as test worms. Results were expressed in terms of time of paralysis and time of death of worms and the activity was compared with albendazole as reference standard &amp; Normal saline served as control. Dose dependent decreased paralyzing time and death time was observed. The results of present study indicated that crude methanolic root extract significantly demonstrated paralysis and also caused death of worms especially at higher concentration of (50 mg/ml), Bauhinia variegata showed the best anthelmintic activity. The use of the roots as anthelmintic has been established and further studies are recommended to isolate the active principles answerable for the activity. KEYWORDS: Anthelmintic activity, Pheretima Posthuma, Bauhinia variegata linn

Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni.

Schistosome parasites kill 250,000 people every year. Treatment of schistosomiasis relies on the drug praziquantel. Unfortunately, a scarcity of molecular tools has hindered the discovery of new drug targets. Here, we describe a large-scale RNA interference (RNAi) screen in adult Schistosoma mansoni that examined the function of 2216 genes. We identified 261 genes with phenotypes affecting neuromuscular function, tissue integrity, stem cell maintenance, and parasite survival. Leveraging these data, we prioritized compounds with activity against the parasites and uncovered a pair of protein kinases (TAO and STK25) that cooperate to maintain muscle-specific messenger RNA transcription. Loss of either of these kinases results in paralysis and worm death in a mammalian host. These studies may help expedite therapeutic development and invigorate studies of these neglected parasites.

Alkoxyamines Designed as Potential Drugs against Plasmodium and Schistosoma Parasites.

Malaria and schistosomiasis are major infectious causes of morbidity and mortality in the tropical and sub-tropical areas. Due to the widespread drug resistance of the parasites, the availability of new efficient and affordable drugs for these endemic pathologies is now a critical public health issue. In this study, we report the design, the synthesis and the preliminary biological evaluation of a series of alkoxyamine derivatives as potential drugs against Plasmodium and Schistosoma parasites. The compounds (RS/SR)-2F, (RR/SS)-2F, and 8F, having IC50 values in nanomolar range against drug-resistant P. falciparum strains, but also five other alkoxyamines, inducing the death of all adult worms of S. mansoni in only 1 h, can be considered as interesting chemical starting points of the series for improvement of the activity, and further structure activity, relationship studies. Moreover, investigation of the mode of action and the rate constants kd for C-ON bond homolysis of new alkoxyamines is reported, showing a possible alkyl radical mediated biological activity. A theoretical chemistry study allowed us to design new structures of alkoxyamines in order to improve the selectivity index of these drugs.

EXPERIMENTAL JUSTIFICATION OF PROSPECTS OF USING THE ENTOMOPATHOGENIC PREPARATION BOVERYN FOR THE PROTECTION OF PINETUM

Objective. Study the possibility and feasibility of using the entomopathogenic fungal preparation Boveryn to protect pinetum from damage by pine silkworms. Methods. Field (collection of vegetation samples on the soil surface from trunk circles of model trees; collection of worms from treecrowns); laboratory (species identification, physiological monitoring). At the same time, physiologically defective samples with signs of diseases and also damaged with by worm entomophages wereremoved. They were distributed according to known characteristics, namely: size of the main capsule and age. The selected materials were placed in gauze cages with common pine branches.Worms of three species of seedworms were selected accordingly, and they were diapaused on treetrunks and in the soil. During the studies, the entomopathogenic fungal preparation Boveryn wasused with a titre of 6 billion spores/g and at a concentration of 0.5 %. Results. It was found that thelevel of entomocidal action of Boveryn against worms of different ages is determined by the speciesand age susceptibility of phytophages, as well as temperature. Accounting of the changes in parameters of the death of worms of the pine silkworm of the third generation over time shows that the population is quite vulnerable to Beauveria bassiana (Bals.) Vuill — the active substance in Boveryn. Actually, the experiment confirmed the feasibility of adding suspensions of the preparation inplaces of diapause of phytophages. At an air temperature in the range of 12–17 °C, at least 50 % ofthe pest population dies in only 9.4–12.5 days. When the temperature increases, the time of deathof worms is reduced. The digital mortality characteristics of pine silkworm worms in the fourth andfifth generations (populations of worms that feed on tree crowns) are quite informative. Conclusion. It is feasible to use Boveryn with appropriate procedure (spraying, etc.) in the areas of extensive spread of pine silkworm to ensure control of the number of pests.

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni.

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors.

Identification of the Anthelmintic Power of Anting-anting Leaf and Starfruit Leaf

Ascariasis is an intestinal infection caused by the parasitic worm Ascaris lumbricoides. Starfruit leaf (Averrhoa bilimbi) and leaf anting-anting (Acalypha indica L) is a plant that is often used as a worm remedy in the community. Starfruit leaves (Averrhoa bilimbi) and Leaf anting-anting (Acalypha indica L) contain several compounds that have the potential as anthelmintics, namely saponins, tannins and flavonoids. The purpose of this study was to determine the effect of ethanol extention of starfruit leaf leaves (Averrhoa bilimbi) and leaf anting-anting (Acalypha indica L) as anthelmintic on the time of death of Ascaris suum Goeze worms in vitro. The method in this study is experimental with post test only group design. Test animals from the study are Ascaris suum. The study was conducted at the Parasitology Laboratory, Medical Laboratory Department, Poltekkes Kemenkes Surabaya in 2019. This study used 6 treatment groups, NaCl 0.9% as a negative control and pirantel pamoate 0.25% as a positive control and ethanol extract of wuluh starfruit leaf and ethanol extract of Anting-anting with concentrations of leaves. 40%, 60%, 80% and 100%. Data were analyzed using the Kolmogrov-Smirnov test, the Anova two way Block Design test, then continued using the Post Hoc test to determine differences between blocks and between treatments, against the time of Ascaris suum worm's death. The average time of death of Ascaris suum caused by ethanol extract of starfruit leaves concentration of 40% for 492.3 minutes and ethanol extract of leaf anting-anting 396.5 minutes, concentration of 60% ethanol extract of wuluh starfruit leaves for 278.5 minutes and leaf extract ethanol leaf anting-anting for 283.5 minutes, 80% concentration of ethanol extract of wuluh starfruit leaf for 141.8 minutes and ethanol extract of anting-anting leaf for 174 minutes, 100% concentration of ethanol extract of wuluh starfruit leaves for 66.75 minutes and extract ethanol leaf anting-anting for 92 minutes. So it can be concluded that the ethanol extract of starfruit leaves has an anthelmintic effect on the Ascaris suum worm more optimum than the ethanol extract of the Anting-anting leaves, because the time required is close to positive control that is 60 minutes. &#x0D; Keywords: anthelmintic; Ascaris suum; starfruit leaf; anting-anting leaf

In Vitro Anthelmintic Activity of Acalypha Indica Leaves Extracts

Anting-anting leaves (Acalypha indica L) is one of the wild plants (weeds) that are often used by the community to treat helminthic diseases such as ascariasis, containing several potentially anthelmintic compounds, namely saponins, tannins and flavonoids. The purpose of this study was to determine the effect of giving Anting-anting leaf extract (Acalypha indica L) as an anthelmintic to the time of death of pork roundworms (Ascaris suum Goeze). The method in this study was pre-experimental with a post test only group design. The subjects of the study were Ascaris suum. The study was conducted at the Parasitology Laboratory of the Surabaya Polytechnic Health Medical Laboratory Technologist Department in December-May 2018. This study used 5 treatment groups, 0.9% NaCl as negative control and 0.25% pirantel pamoate as positive control and 60%, 80% and 100%. Data were analyzed using the Kolmogrov-Smirnov test, then the Kruskal-Wallis test was then continued using a Post-Hoc test to determine the difference in anthelmintic power of ear leaf extract of each concentration with positive control over the time of worm death. The average time of Ascaris suum worm death at a concentration of a concentration of 60% for 228.5 minutes, a concentration of 80% for 174 minutes, and a concentration of 100% for 92 minutes. So it can be concluded that the leaf extract of Acalypha L has an anthelmintic effect on the Ascaris suum worm.&#x0D; &#x0D; Keywords: anthelmintic; Ascaris suum; anting-anting leaf

&lt;p class="HeadingRunIn"&gt;&lt;strong&gt;Observations on the life cycles of aquatic Oligochaeta in aquaria&lt;/strong&gt;&lt;/p&gt;

Observations on the life cycles of aquatic oligochaetes were made in the period 1962–2017 at the Võrtsjärv Limnological Station (Estonia) using small aquaria with sieved profundal mud covered with unaerated water. The aquaria were mostly inseminated with 10 juvenile worms and checked four times a year, changing the mud and eliminating the progeny, until the natural death of the original worms. Besides, mass cultures were kept in bigger aquaria. Many individuals of Tubifex tubifex, T. newaensis, Limnodrilus hoffmeisteri, L. udekemianus, Ilyodrilus templetoni, Psammoryctides barbatus, Spirosperma ferox, Potamothrix moldaviensis, P. vejdovskyi, P. bavaricus, Stylodrilus heringianus and Rhynchelmis tetratheca survived for several years, reproduced repeatedly, and died out one by one during the observation period. In some cases, the most longevous individuals reached an age of up to 8 years (I. templetoni), 10–12 years (T. tubifex), 15–17 years (L. hoffmeisteri, P. barbatus, S. heringianus), or even more than 20 years (L. udekemianus, S. ferox, T. newaensis). Criodrilus lacuum did not reproduce in aquaria, although the oldest individual spent 46 years there. Potamothrix hammoniensis, Lophochaeta ignota, Lamprodrilus isoporus, most naidines and some others did not thrive in aquaria and usually died without reproducing. In a cellar, where temperature conditions imitated seasonal fluctuations in lakes, or when the aquaria were maintained at continuously low temperature, the lifetime of worms was often longer than at room temperature. At elevated temperatures (+25° to +35°C) T. tubifex and L. hoffmeisteri formed cocoons mostly with only 1–2 eggs while their life span was then shorter. Architomic clones of Potamothrix bedoti, Bothrioneurum vejdovskyanum, Aulodrilus pluriseta and A. japonicus survived and propagated for years. The architomic Lumbriculus variegatus was thriving only when fed, e.g., with yeast. Uniparental reproduction by parthenogenesis was observed in T. tubifex, L. hoffmeisteri and S. heringianus kept or reared single. Two special races(?) were noted both within T. tubifex and L. udekemianus.

Dirofilaria immitis possesses molecules with anticoagulant properties in its excretory/secretory antigens.

Dirofilaria immitis is a parasitic nematode that survives in the circulatory system of suitable hosts for many years, causing the most severe thromboembolisms when simultaneous death of adult worms occurs. The two main mechanisms responsible for thrombus formation in mammals are the activation and aggregation of platelets and the generation of fibrin through the coagulation cascade. The aim of this work was to study the anticoagulant potential of excretory/secretory antigens from D. immitis adult worms (DiES) on the coagulation cascade of the host. Anticoagulant and inhibition assays respectively showed that DiES partially alter the coagulation cascade of the host and reduce the activity of the coagulation factor Xa, a key enzyme in the coagulation process. In addition, a D. immitis protein was identified by its similarity to the homologous serpin 6 from Brugia malayi as a possible candidate to form an inhibitory complex with FXa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectrometry. These results indicate that D. immitis could use the anticoagulant properties of its excretory/secretory antigens to control the formation of blood clots in its immediate intravascular habitat as a survival mechanism.

In vivo efficacy of the boron-pleuromutilin AN11251 against Wolbachia of the rodent filarial nematode Litomosoides sigmodontis.

The elimination of filarial diseases such as onchocerciasis and lymphatic filariasis is hampered by the lack of a macrofilaricidal–adult worm killing–drug. In the present study, we tested the in vivo efficacy of AN11251, a boron-pleuromutilin that targets endosymbiotic Wolbachia bacteria from filarial nematodes and compared its efficacy to doxycycline and rifampicin. Doxycycline and rifampicin were previously shown to deplete Wolbachia endosymbionts leading to a permanent sterilization of the female adult filariae and adult worm death in human clinical studies. Twice-daily oral treatment of Litomosoides sigmodontis-infected mice with 200 mg/kg AN11251 for 10 days achieved a Wolbachia depletion > 99.9% in the adult worms, exceeding the Wolbachia reduction by 10-day treatments with bioequivalent human doses of doxycycline and a similar reduction as high-dose rifampicin (35 mg/kg). Wolbachia reductions of > 99% were also accomplished by 14 days of oral AN11251 at a lower twice-daily dose (50 mg/kg) or once-per-day 200 mg/kg AN11251 treatments. The combinations tested of AN11251 with doxycycline had no clear beneficial impact on Wolbachia depletion, achieving a > 97% Wolbachia reduction with 7 days of treatment. These results indicate that AN11251 is superior to doxycycline and comparable to high-dose rifampicin in the L. sigmodontis mouse model, allowing treatment regimens as short as 10–14 days. Therefore, AN11251 represents a promising pre-clinical candidate that was identified in the L. sigmodontis model, and could be further evaluated and developed as potential clinical candidate for human lymphatic filariasis and onchocerciasis.