Nematocidal activity of chitosan nanoparticles conjugated with albendazole against the enteral and parenteral phases of trichinosis in experimentally infected mice.

Trichinosis is a serious parasitic zoonotic disease caused mainly by Trichinella spiralis. The used drugs for treatment of trichinosis showed limited bioavailability and high degree of resistance. Moreover, they have a very poor effect in treatment of encysted larvae. Therefore, there is a need for development of new agents which help in improving the bioavailability of the used drugs and enable them to reach different tissues. This study was designed to assess the use of chitosan nanoparticles (CSNPs) in conjugation with full and half dose albendazole (ABZ) in treatment of intestinal and muscular trichinosis. Albino mice (84 mice) were used to evaluate the efficacy of drugs and divided into seven groups; I: control, II: ABZ (50 mg/kg) treated, III: ABZ (25 mg/kg) treated, IV: ABZ (50 mg/kg) conjugated CSNPs treated, V: ABZ (25 mg/kg) conjugated CSNPs treated, VI: CS treated and VII: CSNPs treated. Parasitological and histopathological examinations were used to evaluate the therapeutic efficacy of the used drugs. Results showed significant reduction of adult Trichinella extracted from intestine of all ABZ treated groups either conjugated or not with the highest reduction rate in group IV followed by group V with percentage of reduction of 99.33% and 98.11%, respectively and marked improvement of histopathological examination. Also, results showed significant reduction of Trichinella larvae extracted from muscles of group IV, V and VII with the highest reduction rate in group IV with percentage of reduction of 100% in muscle larvae and marked improvement of histopathological examination. It was concluded that albendazole full dose conjugated chitosan nanoparticles can be a good candidate drug for treating both intestinal and muscular trichinosis.

Influence of Blastocystis hominis on the small intestine and lactase enzyme activity.

Blastocystis hominis is a cosmopolitan protozoan that has been associated with several gastrointestinal disturbances involving lactose intolerance. However, the underlying pathogenic factors remain indistinct. 20 Swiss albino mice were utilized and assembled into four groups, each of five mice: group-I: received neither infection nor lactose (healthy control), group-II: received a single dose of 10,000 cysts of Blastocystis and lactose diets in a dose of 12.5 g/day/mouse for 7 consecutive days starting from day 14 p.i., group-III: non-infected mice with oral doses of lactose (12.5 g/day/mouse) for 7 consecutive days (positive control), group-IV: infected mice on lactose free diet (negative control). We investigated the histopathological changes using H&E stain.s Also, lactase enzyme activity was measured using spectrophotometry and the production of TNF-α and apoptotic events were explored via immunohistochemistry and compared in the small intestine of all groups. The active inflammatory changes in the infected animals were moderate in the form of loss of villous architecture, increased ILC (P-value > 0.001) besides scattered forms of the parasite as compared to non-infected mice. There was a reduction in lactase enzyme activity p.i. The TNF-α levels were induced p.i. as compared to non-infected mice (P-value > 0.001). The expression of Bax protein was upgraded, while Bcl-2 expression decreased significantly with a reverse in Bax/Bcl2 ratio in infected animals. Blastocystis infection appears to humble lactase enzyme activity via the induction of apoptosis in the epithelial cells of the small intestinal brush border in a TNF-α associative pathway.

Usefulness of Sunlight and Artificial UV Radiation Versus Chlorine for the Inactivation of Cryptosporidium Oocysts: An in Vivo Animal Study.

BACKGROUND: Cryptosporidium is an important waterborne protozoan. AIM: The aim of this study was to investigate the effect of sunlight being the natural source of UV and artificial UV irradiation on Cryptosporidium oocysts versus the effect of chlorination, being the traditional method of water disinfection and to provide an insight into the viability and degree of infectivity of Cryptosporidium oocysts, using an animal model. METHODS: An experimental study including 300 neonatal mice was carried out to investigate the effect of artificial ultraviolet (UV) irradiation and sunlight being the natural source of UV irradiation versus chlorine, the traditionally used water disinfectant on the infectivity of Cryptosporidium oocysts present in water. For each item, nine different exposure times were investigated. Parasitological assessment (Modified Ziehl Neelsen stained stool smears) and histopathological assessment of the excised segments of the small intestine (stained by both Haematoxylin & Eosin and ZN stain) of mice were used to verify the inactivation of oocysts. RESULTS: Cryptosporidium oocysts failed to induce any noticeable infection after 4 hours of artificial UV exposure that provided a UV dose of 10mJ/cm2 and after an 8 hours exposure to sunlight, whereas they showed resistance to disinfection by chlorine. CONCLUSION: The results of the study demonstrate the important role of an 8 hours sunlight exposure of potable water in plastic bottles in achieving complete inactivation of any contaminating Cryptosporidium oocysts, thus offering an applicable, economical and convenient method for the control of cryptosporidiosis especially in developing countries.

Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection.

Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease. Recently, protein tyrosine kinase (PTK) inhibitors have been identified as potent anti-schistosomal and anti-fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma mansoni (S. mansoni) induced liver fibrosis. The present study was designed to assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected mice using different parasitological, histopathological and immunohistochemical studies. Genistein showed a significant reduction (P < .05) in total worm burden, tissue egg load, mean hepatic granulomas diameter and numbers, percentage of collagen and expression of transforming growth factor-beta 1 (TGF-ß 1) in the examined hepatocytes with elevation in percentage of degenerated ova, in comparison to the control groups, in both acute and chronic stages of infection. The best results were obtained when Genistein was combined with PZQ. Therefore, it was concluded that Genistein showed a promising anti-schistosomal and anti-fibrotic properties which could make it one of the new potential targets in chemotherapy against schistosomiasis.

Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice.

The present study was conducted on 200 male mice for the detection of the effect of Atorvastatin on Cryptosporidium spp. infection versus the commercially used drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five consecutive days. Parasitological assessment of the drug effect was done using Modified Z-N staining of stool samples collected from mice. Results revealed a reduction of the number of oocysts shed with percentage of reduction on the 21st day post infection by 53.7%, 67.2%, 70.1% &77.5%, respectively, compared to the infected untreated group. The Nitazoxanide treated group showed 52.7% reduction. In addition, examination of small and large intestinal contents after mice scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%, 70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in Nitazoxanide treated group. The histopathological examination of sections from duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant improvement of the histopathological changes in Atorvastatin treated groups and more remarkable improvement in the groups treated with combined drugs as compared to infected untreated group. Accordingly, the combination of Atorvastatin and Nitazoxanide showed a synergistic effect through reduction of the number of oocysts shed and improvement of the histopathological changes induced by Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs of infected immunosuppressed mice in comparison to that induced by either Nitazoxanide or Atorvastatin alone.