Anthelmintic Research Articles

Anthelmintic mass drug administration in the Kusan Hilir subdistrict, Tanah Bumbu Regency, South Borneo 2021

Background: The evaluation for the deworming programmes or anthelmintic mass drug administration (MDA) had not been done in the Kusan Hilir subdistrict, Tanah Bumbu Regency, South Borneo Province, Indonesia. Objective: This study aimed to evaluate the implementation of anthelmintic MDA helminthiasis in Tanah Bumbu Regency. Methods: This mixed-method research used an observational cross-sectional approach, with descriptive and bivariate analysis for quantitative data and thematic content for qualitative data. Results: From 623 samples, 23(3.69%) subjects had helminth infection with an overall prevalence below the standard(<10%). There were 64.8% of respondents who agreed that taking deworming drugs prevents helminthiasis. In-depth interviews with the managers of the deworming programme in Tanah Bumbu Regency showed that MDA, health promotion, and surveillance or monitoring of helminthiasis were implemented based on Regulation of the Indonesian Ministry of Health (MoH) Number 15/2017. Conclusion: The implementation of the anthelmintic MDA programme in Tanah Bumbu Regency was successful.

Helminth Prevalence in European Deer with a Focus on Abomasal Nematodes and the Influence of Livestock Pasture Contact: A Meta-Analysis.

Deer are susceptible to infection with parasitic helminths, including species which are of increasing economic concern to the livestock industry due to anthelmintic drug resistance. This paper systematically collates helminth prevalence data from deer across Europe and explores patterns in relation to host and parasite species, as well as landscape factors. A livestock pasture contact index (LPCI) is developed to predict epidemiological overlap between deer and livestock, and hence to examine deer helminth fauna in the context of their surrounding environment. Fifty-eight studies comprising fallow (Dama dama), red (Cervus elaphus), roe (Capreolus capreolus) and sika (Cervus nippon) deer were identified. Deer populations in "likely" contact with livestock pasture had a higher mean prevalence of the abomasal nematodes Haemonchus contortus, Ostertagia ostertagi, Teladorsagia circumcincta and Trichostrongylus axei (p = 0.01), which are common in livestock and not primarily associated with deer. Roe deer populations had a higher prevalence of T. circumcincta (p = 0.02) and T. axei (p = 0.01) than fallow deer and a higher prevalence of H. contortus than both red (p = 0.01) and fallow deer (p = 0.02). Liver fluke and lungworm species were present sporadically at low prevalence, while the abomasal nematode Ashworthius sidemi occurred locally at high prevalence. Insights from this research suggest that deer helminth fauna is reflective of their surrounding environment, including the livestock species which inhabit areas of shared grazing. This is explored from an epidemiological perspective, and the prospect of helminth transmission between wild and domestic hosts is discussed, including drug-resistant strains, alongside the role of helminths as indicators relevant to the transmission of other pathogens at the wildlife-livestock interface.

Predicting lung exposure of intramuscular niclosamide as an antiviral agent: Power-law based pharmacokinetic modeling.

Niclosamide, a potent anthelmintic agent, has emerged as a candidate against COVID-19 in recent studies. Its formulation has been investigated extensively to address challenges related to systemic exposure. In this study, niclosamide was formulated as a long-acting intramuscular injection to achieve systemic exposure in the lungs for combating the virus. To establish the dose-exposure relationship, a hamster model was selected, given its utility in previous COVID-19 infection studies. Pharmacokinetic (PK) analysis was performed using NONMEM and PsN. Hamsters were administered doses of 55, 96, 128, and 240 mg/kg with each group comprising five animals. Two types of PK models were developed, linear models incorporating partition coefficients and power-law distributed models, to characterize the relationship between drug concentrations in the plasma and lungs of the hamsters. Numerical and visual diagnostics, including basic goodness-of-fit and visual predictive checks, were employed to assess the models. The power-law-based PK model not only demonstrated superior numerical performance compared with the linear model but also exhibited better agreement in visual diagnostic evaluations. This phenomenon was attributed to the nonlinear relationship between drug concentrations in the plasma and lungs, reflecting kinetic heterogeneity. Dose optimization, based on predicting lung exposure, was conducted iteratively across different drug doses, with the minimum effective dose estimated to be ~1115 mg/kg. The development of a power-law-based PK model proved successful and effectively captured the nonlinearities observed in this study. This method is expected to be applicable for investigating the drug disposition of specific formulations in the lungs.

In-vitro anthelmintic activity of crude extracts of Zingiberaceae species commonly available in Mwanza, Tanzania

Introduction: Resistance to commonly used anthelmintic drugs has been reported in many areas of the world. Natural products are good candidates for discovering more effective anthelmintic compounds. This study assessed the In-vitro activity of extracts from Curcuma longa, Zingiber officinale and Elettaria cardamomum. Methods: This study was an In-vitro experimental study involving Apporrectodea longa earthworms. The worms were treated with 20mls of both distilled water and ethanolic extracts of all plant species (at 20, 40 and 60mg/ml). Albendazole was used as a standard drug. Paralysis and death time were recorded. Results: The paralysis time for water extracts were 0.83 hrs, 1.22 hrs and 3.33 hrs at 20mg/ml for Elettaria cardamomum, Zingiber officinale and Curcuma longa respectively while death time was 2.00 hrs, 1.50 hrs and 7.61 hrs for Elettaria cardamomum, Zingiber officinale and Curcuma longa respectively. The paralysis time for ethanol extracts were 0.50 hrs, 0.58 hrs and 0.70 hrs at 20mg/ml for Elettaria cardamomum, Zingiber officinale and Curcuma longa respectively while death time was 1.00 hrs, 1.00 hrs and 1.64 hrs for Elettaria cardamomum, Zingiber officinale and Curcuma longa respectively. Elettaria cardamomum and Zingiber officinale recorded shorter paralysis time than albendazole at 20mg/ml. Conclusion: Zingiber officinale and Elettaria cardamomum have recorded promising In-vitro activity warranting for pharmacological and toxicological investigations.

Investigation of Anthelmintic Property of Cow Urine Distillate on Ascaris and Trichuris eggs Isolated from Soil

Background: Helminth infection occurs due to contact with contaminated soils and poor hygiene practices. Even though there is immense progression in human medicine, infections that occur due to bacteria, fungi, viruses, and parasites persist as a crucial threat to public health. Over the years, many studies indicated cow urine has antimicrobial activity. Hence, this study looks into anthelminthic property of cow urine in Ascaris spp., and Trichuris spp., eggs. Methods: The soil sample was collected at the riverside, near the toilet area and at the pond area at an aborigine village in Malaysia. Next, floatation technique was used to isolate the helminth eggs and it was identified using a light microscope. The cow urine was prepared as raw cow urine (RCU), evaporated raw cow urine diluted with distilled water (ERCUD), evaporation raw cow urine diluted with saline (ERCUS) and evaporated filtered cow urine diluted with saline (EFCUS).Results: From the soil samples, mainly two types of helminths were found which were Ascaris lumbricoides and Trichuris trichiura. Evaporated cow urine diluted with saline showed the most prominent result in the destruction of helminth eggs.Conclusion: Evaporated cow urine possesses biochemical agents that can be used in the future as anthelmintic agents whereby further studies can be made to explore more possibilities to use cow urine as a potential anthelmintic agent.Keywords: Cow urine; Helminth eggs; Anthelmintic

Pleuro-spinal Hydatid Cyst Masquerading as Spinal Tuberculosis: A Rare Case Report

Introduction: Primary hydatid cyst of the spinal cord is exceedingly rare. Diagnosis at the early stages is difficult as they may be asymptomatic or have mild vague pain. Patients typically present when there are features of cord/root compression. Magnetic resonance imaging (MRI) stands as the primary investigative modality, but even then, preoperative diagnosis might not always be possible as it may resemble other pathological conditions. Methods: This was a case report of a single case with evidence-based discussion. Informed consent was obtained. Case Report: We present a 62-year-old female patient with progressive paraparesis and numbness of bilateral lower limbs. MRI was suggestive of a tubercular pleurospinal lesion at the D9-D10 level. However, intraoperatively, it was identified to be a rare case of primary pleurospinal (thoracic) hydatid cyst. The patient was managed with complete surgical removal of all the cysts and antihelminthic drug therapy with no evidence of recurrence at the 2-year follow-up. Conclusion: Radiological diagnosis might not be accurate and hydatidosis must be kept in mind to avoid intraoperative confusion. Timely diagnosis, appropriate surgical planning, and comprehensive follow-up are crucial for achieving optimal outcomes.

Sulfonamide Bioisosteres of Niclosamide Enhance Antibacterial Activity of Colistin and Bacitracin.

Multicomponent therapy combining antibiotics with enhancer molecules known as adjuvants is an emerging strategy to combat antimicrobial resistance. Niclosamide is a clinically relevant anthelmintic drug with potential to be repurposed for its inherent antibacterial activity against Gram-positive bacteria and its ability to potentiate the antibacterial activity of colistin against susceptible and resistant Gram-negative bacteria. Herein, sulfonamide analogs of niclosamide were prepared and found to enhance colistin activity against Gram-negative bacteria. The ability of niclosamide and the new sulfonamide analogs to synergize with bacitracin against vancomycin-resistant Enterococcus faecium was also discovered.

Prevalence of intestinal schistosomiasis among school children in Biu Local Government Area, Borno State, Nigeria

Intestinal schistosomiasis is one of the neglected tropical diseases caused by four species of the genus Schistosoma. The aim of this study was to determine the prevalence, knowledge and risk factors associated with intestinal schistosomiasis in the study area. A total number offour hundred and twenty (420) fecal samples were collected from the study participants in the three sampling locations; Tum, Buratai and Biu metropolis. Samples collected were examined using formal-ether concentration technique. Other information about the participants’ knowledge on the disease and associated risk factors were obtained using a structured questionnaire. Three 3(0.7%) out of the entire samples examined were found with the eggs of Schistosoma mansoni and only age group 11-13years and 14-16years 1(0.7%) and 2(1.8%) has egg of Schistosoma mansoni in their fecal samples respectively. All the 3(1.6%) infected participants were male while no female 58 participant was infected with the parasite. Miringa had the highest prevalence of (1.9%) followed by Buratai(0.9%) and no infection in Biu metropolis. The difference in the prevalence rate between the age groups, sexes and locations of th eparticipants was statistically not significant. There was high level of ignorance and poor knowledge about the transmission, prevention and treatment of schistosomiasis among the participants. Other parasites encountered during the study were Ascaris lumbricoides (54%) Trichiuris trichiuria (33%), Giardia intestinalis (3%), Entamoeba histolytica (4%), Ancylostoma duodenale (6%). During this study, Schistosomiasis was not endemic in the study area but other intestinal parasites. Therefore, there is need for stakeholders to educate the people on the effect of this parasite and treat the few infected individuals using praziquantel for schistosoma spp and other anthelmintic drugs for mass administration to avoid further escalation of the intestinal parasites in the area.

Phytochemical screening, FTIR and GCMS analysis of Cucurbita pepo seeds cultivated in Kiambu county, Kenya

Bioactive compounds and other constituents of plants have been shown to vary by cultivation region, species, environmental conditions and method of extraction among others. Phytochemical analysis of Cucurbita pepos farmed in Kiambu County, Kenya, or their seeds has not been documented. The present research aimed to bridge this knowledge gap by screening phytochemicals and characterizing the seed extracts of Cucurbita pepo cultivated in Kiambu County, Kenya. Cucurbita pepo seeds extracted using organic solvent extraction method employing methanol and preconcentrated in a vacuum rotatory evaporator. The extracts were characterized by GCMS and Fourier transform infrared (FTIR) techniques. Phytochemical analysis of the seeds revealed the presence of flavonoids, alkaloids, saponins, cardiac glycosides, and steroids. FT-IR analysis showed significant peaks for C–N, N–H, C–O, C–H, and CH3 functional groups. The GCMS studies revealed a significant number of fatty acids and their derivatives with 12-cis-octadecadienoate being the most abundant in the oil (53.93 %). A significant amount of the macrocyclic lactone 7,9-ditert-butyl-1-oxaspiro [4.5] deca-6,9-diene-2,8-dione (0.58 %) in the seeds was reported. Macrocyclic lactones are generally a class of anthelminthic drugs. These reported biologically active compounds have a wide range of medicinal and nutritional value. One interesting compound from the GCMS analysis of the seed extracts analyzed was the macrocyclic lactone providing a basis for further research on the anthelminthic actions of the seeds.

Oxfendazole Nitazoxanide combination in experimental neurocysticercosis – Anti-inflammatory and cysticidal effects

Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after in vivo treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with T. crassiceps cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.

Anthelmintic activity and chemical profile of native plant extracts from the Yucatan Peninsula against Toxocara canis

Toxocara canis can produce the “larva migrans” syndrome in humans, and in puppies, it can cause severe digestive disorders. The most used treatments are based on anthelmintics, although there are reports of anthelmintic (AH) resistance. The Yucatan Peninsula has a great variety of plant species whose AH properties are still unknown. The objective of this study was to evaluate the in vitro AH activity of ethanolic (EE), methanolic (ME) and aqueous (AE) extracts from the leaves of five native plant species of the Yucatan Peninsula on T. canis eggs of dogs from Merida, Yucatan. As part of a screening, the EE of the plants Alseis yucatanensis, Calea jamaicensis, Cameraria latifolia, Macrocepis diademata, and Parathesis cubana were evaluated at doses of 2400 and 3600 μg/ml. The EE and AE of A. yucatanensis and M. diademata presented high percentages (≥ 91.3%) of inhibition of the larval development of T. canis after six days of exposure. The lowest LC50 and LC99 was presented by the ME from A. yucatanensis (255.5 and 629.06 µg/ml, respectively) and the ME from M. diademata (222.4 and 636.5 µg/ml, respectively), and the AE from A. yucatanenesis (LC50 of 535.9 µg/ml). Chemical profiling of the most potent AH extract (Alseis yucatanensis) was carried out by LC-UV-HRMS. Data from the ME and AE from this plant indicated the presence of the known glucosylngoumiensine, kaempferol 3,7-diglucosyde, uvaol, linoleic acid and linolenic acid together with unknown alkaloids. The EE, ME and AE from leaves of M. diademata and A. yucatanensis could be developed as natural alternatives to control T. canis.

Comparison between a complete preconditioning programme and conventional conduct on behaviour, health and performance of young bulls from small cow-calf herds

Bovine respiratory diseases (BRDs) have major socioeconomic impacts in the beef sector. Antimicrobials have been traditionally used to prevent the development of BRDs upon arrival in fattening units. Currently, from a “One Health and One Welfare” perspective, alternative solutions are being investigated. Preconditioning programmes that aim at reducing stress and reinforcing immune functions have been proposed to decrease BRDs incidence. In this study, we assessed the effect of a preconditioning protocol set up in nine commercial beef herds on young bulls’ behaviour, health, and performance. Preconditioned bulls (PREC) were weaned indoors 50 days before departure, and progressively fed a concentrate diet supplemented with vitamins and trace elements. They also received an anthelmintic treatment, and two doses of a trivalent vaccine against respiratory pathogens at 4-week intervals. In contrast, controls (CTRL) were kept on pasture with their dams with no vaccination or particular diets. All calves were transported together to a single sorting facility to be sorted by experimental groups, origins, and BW, forming new groups before dispatch to four fattening units. At arrival, CTRL were treated with anthelmintic drugs and received one injection of the same BRDs vaccine. No intervention was performed on PREC bulls. BRD-scores were 0.73 in PREC versus 0.07 in CTRL (P = 0.01) during the preconditioning period and 0.96 in PREC versus 0.54 in CTRL (P = 0.41) after 15 days in the fattening units. Morbidity estimates were 18% in PREC versus 1% in CTRL (P < 0.001) during the preconditioning period and 32% in PREC versus 19% (P = 0.07) in CTRL after 15 days in the fattening units. Poor housing conditions during preconditioning and a different aetiology could partly explain these results. At arrival to fattening, the average daily gain (ADG) was 1 605 g for PREC versus 1 140 g (P = 0.012) for CTRL. After fattening for 180 days, differences in BW, ADG, carcass weight and conformation were inconclusive. In Europe, preconditioning programmes including vaccination must be set up coherently with good husbandry practices and with a global adaptation of batch management of the beef sector otherwise, they may be less effective than expected.

Structure - Guided design of arctigenin derivatives against infections of Gyrodactylus kobayashii

Gyrodactylosis is a widespread parasitic illness that affects fish in both farming and natural environments. The current chemotherapy approaches are not always satisfactory, so the development of new anthelmintic agents is necessary. Arctigenin, a natural lignan found in various plants, possesses a multitude of biological activities. Previous research has demonstrated that arctigenin targets the protein myosin in Gyrodactylus kobayashii. Building upon this interaction, we designed 31 derivatives of arctigenin using Discovery Studio. The ester derivatives exhibited significant anthelmintic activity, with C-21 displaying the highest activity, boasting an EC50 of 0.4 mg/L. Furthermore, we conducted an investigation into the mechanism by which C-21 affects the parasite and discovered that it disrupts the muscular structure of the parasite's body surface, thus inhibiting its energy production and myosin expression, ultimately leading to the parasite's demise. In conclusion, C-21 exhibits promising potential as an agent for controlling Gyrodactylus kobayashii infection.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN PRESUMED VETERINARY ANTHELMINTIC DRUG-INDUCED RETINAL TOXICITY: A Glimpse into Underlying Mechanism.

To report optical coherence tomography findings of presumed veterinary anthelmintic drugs (VADs)-induced retinal toxicity that may aid in understanding potential pathogenic mechanisms. This is a retrospective observational case series analysis of patients with vision abnormalities following the accidental or intentional consumption of veterinary anthelmintic drugs. All cases underwent a thorough ophthalmological examination. Moreover, medical records, as well as the initial and follow-up optical coherence tomography images, were thoroughly scrutinized. Four patients were identified (3 men; mean [range] age, 36.5 [22-52] years). Each patient overdosed on one or two of the following VADs: closantel, triclabendazole, praziquantel, pyrantel pamoate, and niclofolan. The most characteristic optical coherence tomography finding was diffuse, granular, hyperreflective lesions throughout the outer retina, which were initially identified in the ellipsoid zone in two cases. At follow-up, optical coherence tomography exhibited regression of hyperreflective lesions and extensive loss of the outer retinal elements in two patients. In addition, the subfoveal outer retinal layers may be partially preserved. Some veterinary anthelmintic drugs could be detrimental to the human retina if overdosed, resulting in visual disturbances. Optical coherence tomography revealed the mitochondria-enriched ellipsoid zone where outer retinal damage first appeared on, implying that these medications may harm the retina by inhibiting mitochondrial energy metabolism, as they do to eliminate parasites.

Anthelmintic Activity of Saussurea costus (Falc.) Lipsch. Against Ascaridia galli, a Pathogenic Nematode in Poultry: In Vitro and In Vivo Studies.

The growing resistance of helminth parasites to currently available commercial anthelmintic drugs, combined with apprehensions regarding detrimental chemical residues in livestock products, has sparked an interest in exploring medicinal plants as an alternative strategy for treating helminthiasis. As a result, this study was designed to investigate the anthelmintic activity of crude methanolic extracts (CME) of Saussurea costus root on Ascaridia.galli, a pathogenic nematode of poultry. In vitro, the anthelmintic effect of Saussurea costus root was evaluated in comparison to commercial anthelmintic, levamisole on the adult nematode parasites, A.galli using worm motility inhibition (WMI) test. The CME of S.costus was also evaluated for in vivo anthelmintic activity in chickens experimentally infected with Ascaridia galli. For the in vivo study, one hundred-day-old chickens were orally infected with embryonated eggs of A. galli worms. The efficacy of the plant extract as an anthelmintic was assessed through two tests: faecal egg count reduction (FECR) test and worm count reduction (WCR) test. The study investigated three distinct doses of plant extract under in vivo setup: 500mgkg-1 body weight (bw), 1000mgkg-1 bw, and 2000mgkg-1 bw. In vitro, all the tested concentrations of S.costus (25mg/ml, 50mg/ml, and 100mg/ml) showeda significant (P < 0.001) anthelmintic effects on live adult A. galli worms in terms of inhibition of worm motility at different hours post-treatment. At the highest concentration of the extract, we observed worm motility inhibition of 100% at 24h post-exposure. On day 14 post-treatment, all birds were slaughtered, and adult A. galli worms were subsequently retrieved from their small intestines. Birds treated with CME extract of S. costus root exhibited a significant (P < 0.001) reduction in faecal egg count. However, the administration of the extract at the dosage of 500mgkg-1bw to the birds did not reveal any significant (P > 0.05) differences in the worm count compared to the negative control group. The CME of S. costus at a dose of 2000mgkg-1bw showed the highest anthelmintic activity by inducing 83.10% FECR and 76.47% WCR. In conclusion, the root extract of S. costus has a promising anthelmintic activity on A. galli as demonstrated by the results of the present experiment.

Ablation of Wnt signaling in bone marrow stromal cells overcomes microenvironment-mediated drug resistance in acute myeloid leukemia

The survival of leukemic cells is significantly influenced by the bone marrow microenvironment, where stromal cells play a crucial role. While there has been substantial progress in understanding the mechanisms and pathways involved in this crosstalk, limited data exist regarding the impact of leukemic cells on bone marrow stromal cells and their potential role in drug resistance. In this study, we identify that leukemic cells prime bone marrow stromal cells towards osteoblast lineage and promote drug resistance. This biased differentiation of stroma is accompanied by dysregulation of the canonical Wnt signaling pathway. Inhibition of Wnt signaling in stroma reversed the drug resistance in leukemic cells, which was further validated in leukemic mice models. This study evaluates the critical role of leukemic cells in establishing a drug-resistant niche by influencing the bone marrow stromal cells. Additionally, it highlights the potential of targeting Wnt signaling in the stroma by repurposing an anthelmintic drug to overcome the microenvironment-mediated drug resistance.

Diet modulates strongyle infection and microbiota in the large intestine of horses.

The use of anthelminthic drugs has several drawbacks, including the selection of resistant parasite strains. Alternative avenues to mitigate the negative effects of helminth infection involve dietary interventions that might affect resistance and/or tolerance by improving host immunity, modulating the microbiota, or exerting direct anthelmintic effects. The aim of this study was to assess the impact of diet on strongyle infection in horses, specifically through immune-mediated, microbiota-mediated, or direct anthelmintic effects. Horses that were naturally infected with strongyles were fed either a high-fiber or high-starch diet, supplemented with either polyphenol-rich pellets (dehydrated sainfoin) or control pellets (sunflower and hay). When horses were fed a high-starch diet, they excreted more strongyle eggs. Adding sainfoin in the high-starch diet reduced egg excretion. Additionally, sainfoin decreased larval motility whatever the diet. Moreover, the high-starch diet led to a lower fecal bacterial diversity, structural differences in fecal microbiota, lower fecal pH, lower blood acetate, and lower hematocrit compared to the high-fiber diet. Circulating levels of Th1 and Th2 cytokines, lipopolysaccharides, procalcitonin, and white blood cells proportions did not differ between diets. Overall, this study highlights the role of dietary manipulations as an alternative strategy to mitigate the effect of helminth infection and suggests that, in addition to the direct effects, changes in the intestinal ecosystem are the possible underlying mechanism.

Evaluation of the Protoscolicidal Activity of Humulus lupulus Methanolic Extracts on Echinococcus granulosus Sensu Stricto.

The larval stage of the parasite Echinococcus granulosus sensu lato (s.l) is responsible for cystic echinococcosis (CE), a long-term infection affecting humans and animals worldwide, and constitutes a serious public health concern. If left untreated, CE can cause serious damage to multiple organs, especially the liver and lungs. Regarding the treatment, in the last few years, the use of pharmacological treatment has increased, suggesting that in the future, drug therapy may replace surgery for uncomplicated cysts. However, the only available anthelmintic drug to treat this infection is the albendazole, which has an efficacy that does not exceed 50%. On the basis of the above-mentioned evidence, new and improved alternative treatments are urgently needed. The use of natural products and their active fractions and components holds great promise as a valuable resource for the development of novel and effective therapies. Hop (Humulus lupulus L.) is a bittering agent in the brewing industry for which the sedative, digestive, anti-inflammatory, and antimicrobial effects have been reported. The purpose of this study was to assess the in vitro efficacy of methanolic extracts from the leaves of hop varieties against E. granulosus sensu stricto (s.s) protoscoleces. Varieties Mapuche and Victoria caused a stronger protoscolicidal effect compared to the Bullion, Cascade, and Traful varieties (P < 0.01), coinciding with their highest content of flavonoids, total polyphenols, and saponins. The viability of protoscoleces treated with the varieties Mapuche and Victoria decreased to approximately 50% at days 5 y 8, respectively, showing alterations such as soma contraction and impaired microtriches. After 18 days of treatment with both varieties, protoscoleces were completely altered both structurally and ultrastructurally. In conclusion, the methanolic extracts of the H. lupulus varieties Mapuche and Victoria demonstrated a marked in vitro effect against E. granulosus s.s. protoscoleces. The beer-making industry exclusively uses hop cones, leaving behind large amounts of hop leaves as an agricultural by-product that is not being utilized. On the basis of our study, we propose that hop leaves could also be used as a source of secondary metabolites with anthelmintic activity.

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

Diagnosis, Hematologic Profile, and Treatment of Cystoisosporiasis in Domestic Dog

Cystoisosporiasis infection is caused by Cystoisospora spp. or Isospora spp. in dogs. Cystoisospora spp. are protozoa ordo Eucoccidiorida. Cystoisosporiasis is considered more risky in puppies. Clinical manifestations of cystoisosporiasis tend to be watery diarrhea to melena in puppies which can also be concurrent with vomiting, and tenesmus, whereas in adult dogs known as symptomatic. A female domestic dog, aged &gt;1 yo was kept indoors and had not been vaccinated or anthelmintic drugs. The dog has changed in the consistency of slightly soft feces with a frequency of defecation 1–2 times a day. Diagnose performed using microscopic fecal examination with the floating method found the presence of Cystoisospora spp. oocysts, followed by the calculation of oocysts per gram (OPG) using a two-chamber McMaster to determine the degree of Cystoisospora spp. infection. Blood examination showed leukocytosis, granulocytosis, and hypochromic anemia. The treatment was administered of 15 mg/kg BW sulfadiazine orally every 12 hours for 7 days, 14 mg/kg BW metronidazole every 12 hours for 7 days, and 300 mg Hemafort® every 24 hours for 7 days. After 7 days of treatment, we reported normal fecal consistency and negative parasitic manifestation. Prevention was done by paying attention to treatment, immediately identifying the presence of oocysts, educating owners to avoid animal distress, and maintaining a good hygiene environment.