Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Efficacy of artemether against toxocariasis in mice: parasitological and immunopathological changes in brain, liver, and lung.

Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15th dpi (early treatment), and at the 35th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.

Trichinella spiralis: A new parasitic target for curcumin nanoformulas in mice models.

Trichinosis spiralis is a global disease with significant economic impact. Albendazole is the current-treatment. Yet, the world-widely emerging antimicrobial resistance necessitates search for therapeutic substitutes. Curcumin is a natural compound with abundant therapeutic benefits. This study aimed to evaluate the potential of crude-curcumin, chitosan and for the first time curcumin-nano-emulsion and curcumin-loaded-chitosan-nanoparticles against Trichinella spiralis adults and larvae in acute and chronic trichinosis models. Trichinosis spiralis was induced in 96 Swiss-albino mice. Infected mice were divided into 2 groups. Group I constituted the acute model, where treatment started 2 h after infection for 5 successive days. Group II constituted the chronic model, where treatment started at the 30th day-post-infection and continued for 10 successive days (Refer to graphical abstract). Each group contained 8 subgroups that were designated Ia-Ih and IIa-IIh and included; a; Untreated-control, b; Albendazole-treated (Alb-treated), c; Crude-curcumin-treated (Cur-treated), d; Curcumin-nanoemulsion-treated (Cur-NE-treated), e; Albendazole and crude-curcumin-treated (Alb-Cur-treated), f; Albendazole and curcumin-nanoemulsion-treated (Alb-Cur-NE-treated), g; Chitosan-nanoparticles-treated (CS-NPs-treated) and h; Curcumin-loaded-chitosan-nanoparticles-treated (Cur-CS-NPs-treated). Additionally, six mice constituted control-uninfected group III. The effects of the used compounds on the parasite tegument, in-vivo parasitic load-worm burden, local pathology and MDA concentration in small intestines of acutely-infected and skeletal muscle of chronically-infected mice were studied. Results showed that albendazole was effective, yet, its combination with Cur-NE showed significant potentiation against adult worms and muscle larvae and alleviated the pathology in both models. Cur-CS-NPs exhibited promising results in both models. Crude-curcumin showed encouraging results especially against muscle larvae on long-term use. Treatments effectively reduced parasite load, local MDA level and CD31 expression with anti-inflammatory effect in intestine and muscle sections.

Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice.

There are currently insufficient anthelmintic medications available for the treatment of toxocariasis. For instance, Albendazole (ABZ) is the preferred medication, but its effectiveness against tissue-dwelling parasites is limited. In addition, Metformin (MTF) is a widely used oral antidiabetic medication that is considered to be safe for treatment. This study aimed to investigate any potential effects of MTF, alone or in combination with ABZ, on mice infections caused by Toxocara canis (T. canis). The efficacy of the treatment was assessed in the acute and chronic phases of the infection by larval recovery and histopathological, immunohistochemical, and biochemical studies. The results showed that combined therapy significantly reduced larval counts in the liver, brain, and muscles and ameliorated hepatic and brain pathology. It reduced oxidative stress and TGF-ß mRNA expression and increased FGF21 levels in the liver. It decreased TNF-α levels and MMP-9 expression in the brain. In addition, it increased serum levels of IL-12 and IFN-γ and decreased serum levels of IL-4 and IL-10. In the acute and chronic phases of the infection, the combined treatment was more effective than ABZ alone. In conclusion, this study highlights the potential role of MTF as an adjuvant in the treatment of experimental T. canis infection when administered with ABZ.

Parasitic infections as potential risk factors for attention deficit hyperactivity disorder (ADHD) in children.

Attention deficit hyperactivity disorder (ADHD) represents a mysterious neuropsychiatric alarming concern due to indefinite etiopathogenesis among children. Notably, the studies which investigated the correlation between ADHD and parasitic infections are insufficient. Therefore, this research aimed to assess the correlation between ADHD and some tissue dwelling and intestinal parasitic infections in children. The study was conducted on 200 children, including 100 children suffering from ADHD (Group I) and 100 healthy children as a control group (Group II). All caregivers fulfilled predesigned sociodemographic form and Conners parent rating scale (CPRS-48) questionnaire. Blood samples were collected to determine hemoglobin level as well as relative eosinophilic count. The presence of anti-Toxoplasma IgG and anti-Toxocara IgG in serum by Enzyme-Linked Immunosorbent Assay (ELISA) was further investigated. Also, micronutrients as zinc, iron, and copper levels were measured. Schistosoma antigen was investigated in urine samples. Stool samples were subjected to direct wet smear, concentration technique and modified Ziehl-Neelsen (MZN) staining for coccidian parasites detection. Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica antigens were investigated in stool samples. Group I expressed more liability to sociodemographic risk factors, decreased levels of Hb, iron, zinc, and copper with statistically significant difference (P < 0.001). Comparison between Group I and Group II regarding the detected parasitic infections exhibited statistically significant difference except Schistosoma antigen positivity which expressed no statistical significance. The present study concluded that the parasitic infections with their consequences are potential risk factors in children with ADHD indicating that their early diagnosis and treatment may help in ADHD prevention.

Novel insights on the therapeutic effect of levamisole on the chronic toxoplasmosis in mice model.

Latent toxoplasmosis mostly reactivates which could result in acute encephalitis. Chronic toxoplasmosis treatments are severely constrained by Toxoplasma cyst resistance. Novel therapeutic approaches are therefore becoming more essential. In this study, the effects of levamisole (LEVA) and spiramycin on the early and late stages of experimental toxoplasmosis are investigated. MATERIALS AND METHODS: Seventy-five Me49 Toxoplasma gondii infected Swiss albino mice were divided into five groups; (GI): noninfected control group; (GII): infected untreated control group; (GIII): infected- LEVA treated group; (GIV): infected and received combination of spiramycin and LEVA and (GV): infected-spiramycin treated group. The impact was assessed through brain cyst count by Quantitative Real-Time Polymerase Chain Reaction (PCR), interferon gamma (IFN-γ) assay, histopathological study, and total blood counts. RESULTS: The progression of chronic toxoplasmosis could only be partially controlled by using either levamisole or spiramycin as a separate drug. The combined spiramycin and levamisole treatment significantly decreased the burden of Toxoplasma brain cyst, increased IFN-γ level, total blood parameters and improved the histopathological features especially at the late stage of infection. IN CONCLUSION: Levamisole effectively modulated Toxoplasma-induced immune responses, resulting in chronic toxoplasmosis remission. Further clinical trials will be needed to study the effect of these combination in HIV/AIDS (human immunodeficiency virus) patients with toxoplasmosis.

Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study.

BACKGROUND: Toxoplasmosis is a deleterious parasitic disease with harmful impact on both humans and animals. The present study was carried out to evaluate the antiparasitic effect of chloroquine (CQ), spiramycin (SP), and combination of both against the highly virulent RH HXGPRT (-) strain of Toxoplasma gondii (T. gondii) and to explore the mechanisms underlying such effect. METHODS: We counted the tachyzoites in the peritoneal fluid and liver smears of mice and performed scanning and transmission electron microscopy and immunofluorescence staining of tachyzoites. Moreover, relative caspase 3 gene expression was measured by real time polymerase chain reaction of liver tissues and immunoassay of anti-apoptotic markers [B cell lymphoma-2 (Bcl-2) and X-chromosome linked inhibitor of apoptosis (XIAP)] and interferon gamma (IFN-γ) was done in liver tissues by ELISA. In addition, we estimated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) and performed histopathological examination of liver sections for scoring of inflammation. RESULTS: We found that both CQ and CQ/SP combination significantly reduced parasitic load in the peritoneal fluid and liver smears, induced apical disruption of tachyzoites, triggered host cell apoptosis through elevation of relative caspase 3 gene expression and suppression of both Bcl-2 and XIAP. Also, they upregulated IFN-γ level, reduced serum AST and ALT, and ameliorated liver inflammation. CONCLUSIONS: Either of CQ and CQ/SP combination was more effective than SP alone against T. gondii with the CQ/SP combination being more efficient. Therefore, adding CQ to other anti-Toxoplasma therapeutic regimens may be considered in future research.