The interaction of Schistosoma mansoni infection with diabetes mellitus and obesity in mice.

Human schistosomiasis is one of the most prevalent parasitic diseases worldwide. Various host factors can affect the host-parasite interactions. Therefore, the aim of the present work was to determine the parasitological, histopathological, biochemical, and immunological status of Schistosoma mansoni-infected hosts with metabolic disorders to identify the underlying possible mechanisms of these comorbidities. The study animals were divided into four groups. Group I represented the control groups, namely, the normal control group, the S. mansoni-infected control group, and the noninfected type 1 diabetes (T1DM), type 2 diabetes (T2DM), and obesity groups. The mice of the other three groups underwent induction of T1DM (Group II), T2DM (Group III) and obesity (Group IV) before being infected with S. mansoni. All mice were subjected to body weight measurement, blood glucose and insulin assessment, parasitological evaluation of adult worm count, tissue egg count and intestinal oogram. Histopathological and immunohistochemical study using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells (HSCs) and image analysis of Masson's trichrome-stained liver sections using ImageJ (Fiji) software were carried out. Additionally, immunological analysis of tumour necrosis factor (TNF) beta, interleukin-5 (IL-5), IL-10, Forkhead box P3 (FOXP3) and pentraxin 3 (PTX3) levels besides biochemical study of total lipid profile were evaluated. The present study revealed a significant increase in the adult worm count and tissue egg output in the obesity group compared to the infected control group. The oogram of counted eggs showed prevalence of immature eggs in T1DM group, while T2DM and obese groups showed prevalence of mature eggs. The fibrosis area percentage showed significant increase in T2DM and obese groups while it was decreased in T1DM group in comparison to infected control group. Our data also showed significant increase in the levels of TNF-ß, IL-5, PTX3 in T1DM, T2DM and obesity groups in comparison to infected control group, whilst the levels of FOXP3 and IL-10 were increased in the infected groups in comparison to their noninfected controls. Moreover, infected T1DM, T2DM and obesity groups showed higher blood glucose and lipid profile in comparison to the infected control group. However, these parameters were improved in comparison to their noninfected controls. In sum, induction of T2DM and obesity increased tissue egg counts, mature egg percentage, and fibrosis density, while schistosome infection induced changes in the lipid profile and blood glucose levels in infected diabetic and obese groups and impacted favorably insulin levels in obese mice. By better understanding the complexities of host-parasite interactions, efforts to reduce the burden of these debilitating diseases can be improved.

Human umbilical cord blood mesenchymal stem cells as a potential therapy for schistosomal hepatic fibrosis: an experimental study.

The objective of our study was to assess the effect of human umbilical cord blood (HUCB) mesenchymal stem cells (MSCs) transplantation on schistosomal hepatic fibrosis in mice. The study animals were divided into three groups. Group I is a control group, where the mice were infected with Schistosoma mansoni cercariae and remained untreated. The mice of the other two groups were infected and treated with either praziquantel (Group II) or HUCB-MSCs (Group III). Liver function tests, as well as histopathological evaluation of liver fibrosis using hematoxylin and eosin and Masson's trichrome stains, were performed. Additionally, an immunohistochemical study was carried out using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells. Compared to the control group, the treated (praziquantel and MSCs) groups showed a substantial improvement, with a significant difference regarding the histopathological evaluation of liver fibrosis in the MSCs-treated group. In conclusion, MSCs could be a promising and efficient cell therapy for liver fibrosis.

Hybrid feature extraction techniques for microscopic hepatic fibrosis classification.

Chronic liver diseases' hallmark is the fibrosis that results in liver function failure in advanced stages. One of the serious parasitic diseases affecting the liver tissues is schistosomiasis. Immunologic reactions to Schistosoma eggs leads to accumulation of collagen in the hepatic parenchyma causing fibrosis. Thus, monitoring and reporting the staging of the histopathological information related to liver fibrosis are essential for accurate diagnosis and therapy of the chronic liver diseases. Automated assessment of the microscopic liver tissue images is an essential process. For accurate and timeless assessment, an automated image analysis and classification of different stages of fibrosis can be employed as an efficient procedure. In this work, granuloma stages, namely cellular, fibrocellular, and fibrotic granulomas along with normal liver samples were classified after features extraction. In this work, a new hybrid combination of statistical features with empirical mode decomposition (EMD) is proposed. These combined features are further classified using the back-propagation neural network (BPNN). A comparative study of the used classifier with the support vector machine is also conducted. The comparative results established that the BPNN achieved superior accuracy of 98.3% compared to the linear SVM, quadratic SVM, and cubic SVM that provided 85%, 84%, and 80%; respectively. In conclusion, this work is of special value that provides promising results for early prediction of the liver fibrosis in schistosomiais and other fibrotic liver diseases in no time with expected better prognosis after treatment.

Implication of artemisinin nematocidal activity on experimental trichinellosis: In vitro and in vivo studies.

Benzimidazole drugs are used for treatment of trichinellosis, but they have a limited effect against encapsulated larval stages of Trichinella spiralis. Hence, there is a considerable interest in developing new anthelmintic drugs. Our aim is to investigate the possible effect of artemisinin on T. spiralis in in vitro and in vivo studies. T. spiralis worms were isolated from infected mice and transferred to 3 culture media; group I: with no drugs, group II: contained artemisinin and group III: contained mebendazole, then they were subjected to electron microscopic study. An in vivo study was done where mice were divided into three groups; group I: infected and untreated, group II: received artemisinin and group III: received mebendazole. The efficacy of treatment was assessed by adult and total larval counts, histopathological study of the small intestinal and muscle tissues and immunohistochemical staining of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in muscles. Adult worm teguments showed significant degeneration and destruction with both drugs. Also, significant reduction of total adult and larval counts occurred in treated groups in comparison to the control group. Histopathological examination of the small intestine and muscles showed marked improvement with reduction in the inflammatory infiltrates with both drugs. COX-2 and VEGF expressions were reduced in both treated groups with more reduction in the artemisinin-treated group. This study revealed that artemisinin has the potential to be an alternative drug against trichinellosis.

Nitazoxanide anthelmintic activity against the enteral and parenteral phases of trichinellosis in experimentally infected rats.

Most of the drugs used for the treatment of trichinellosis show a limited bioavailability and a high degree of resistance. Therefore, this study aimed to characterize the anthelmintic potential activity of nitazoxanide (NTZ) in a rat model of experimental trichinellosis. Animals were divided into three groups; group I, infected and non-treated; group II, received NTZ for three days post-infection (dpi) and group III, received NTZ 30 dpi for 14 consecutive days. Treatment efficacy was assessed by Trichinella spiralis adult and larval counts, histopathological studies of the small intestine and muscles and inducible nitric oxide synthase (iNOS) expression in the small intestine. T. spiralis adult count was reduced in NTZ -treated group (66.6%) and the larval count decreased to 68.7 and 76.7% in the early and late treatment, respectively. The infected non-treated rats showed massive inflammatory cellular infiltration in the small intestines and muscles. This inflammatory response was minor in the treated groups and was accompanied by a decrease in iNOS expression. Moreover, in group III, the larvae were replaced by homogenized substance with some destructive changes in the capsule. In conclusion, NTZ showed a promising activity against enteral and more effect in parenteral phases of trichinellosis.

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis.

Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.

Atorvastatin and metformin administration modulates experimental Trichinella spiralis infection.

The host-parasite interaction can be altered by the changes in the host environment that may be or may not be in favor of successful invasion by the nematode parasite Trichinella spiralis. Metformin and atorvastatin are applied on a wide scale, to the degree that they could be considered as part of the host biochemical environment that can affect the parasite. Therefore, this study aimed to investigate the impact of alteration of the host's biochemical environment by these commonly used drugs upon the course of T. spiralis infection. Mice were divided into three groups: (1) received atorvastatin, (2) received metformin, and (3) untreated, then after one week, animals were infected with T. spiralis. The treatment continued until the end of the experiment. From each group, small intestines and muscles were removed for histopathological, immunohistochemical, and biochemical analyses as well as total muscle larval counts. We found that the oxidative stress and the expression of vascular endothelial growth factor (VEGF) in the muscles were significantly reduced in both drug-receiving groups, while the total larval counts in muscles were only significantly reduced in atorvastatin-receiving group as compared to the infected control group. Moreover, marked reduction in the inflammatory cellular infiltration, cyclooxygenase-2 (COX-2) expression, and oxidative stress was noted in the small intestines of the treated groups as compared to the infected control group. In conclusion, this study provides many insights into the different biochemical changes in the host that the parasite has to face. Moreover, the anti-inflammatory and anti-angiogenic effects should be taken into consideration when treating infections in patients on therapy with atorvastatin or metformin.

An experimental study for evaluating the efficacy of cercarial vaccine against Schistosoma mansoni.

This study assessed the effectiveness of autoclaved cercarial vaccine (ACV) in protection against Schistosoma mansoni infection in 125 Swiss albino mice classified into two main groups: GI: a control group. GII: a test vaccinated with ACV, in a single dose of 0.1 ml of 10(4) ml ACV (G.IIa), double dose; 0.2ml (G.IIb) and two single doses 2 weeks apart (G.IIc). Four weeks later, all mice were challenged with S. mansoni cercariae and sacrificed 10 weeks post infection (P.I.). The results revealed that the vaccine in a single dose (G.IIa) induced a high level of protection against S. mansoni infection. There was a significant reduction in the mean number of adult worm (91.12%), ova/gram liver (91.87%), ova/gram intestine (89.09%) and number & size of granulomas in liver (92.92% & 43.53% respectively). Besides, ACV induced a significant increase in the level of IL-10 mRNA expression as compared to the control group.