ABSTRACT
Muscular trichinellosis is a crippling disease, and it is not satisfactorily treated by the anti-parasitic drug albendazole. Trichinella spiralis larvae can survive for long time in muscle phase by formation of fibrous [collagenous] capsule around it, for their protection from host immune system. Colchicine, is a well known antifibrotic that is used long time ago in different fibrotic diseases, and proved recently to be safe for use even in long durations. Also, alpha-chymotrypsin is one member of proteinase enzymes that were proved to cause degradation of extracellular matrix components. So, this study aimed to investigate the effect of adding these antifibrotic agents to albendazole during treatment of muscular trichinellosis. The study was performed on 175 albino mice comprising 7 equal groups 25 mice each. Mice from groups I to VI were infected by T.spiralis larvae orally [200larvae / mouse], group VII served as the healthy non infected group for comparison of biochemical and immunohistochemical results. Group II was treated by albendazole alone orally for three successive days, groups III, IV were given alpha-chymotrypsin intramuscularly and colchicine orally respectively, for four weeks. Groups V,VI were given combined therapy of albendazole and alpha-chymotrypsin and albendazole and colchicine respectively for four weeks. Assessment of results was achieved through; parasitological, biochemical and immunohistochemical studies. Total larval count was done to all studied infected groups, measurement of tissue markers of fibrosis'' muscle hydroxyproline and [MMP-2]'', and also immunohistochemical staining of collagen type IV and fibronectin was done to both infected groups and the non infected one for comparison. Statistical analysis was performed to determine differences between studied groups in different measured parameters. In groups treated with combination therapy [albendazole and alpha-chymotrypsin, ''group V'' and albendazole and colchicine'' group VI''], there was a marked reduction in total larval count, reduction of muscular hydroxyproline levels, elevation of muscular MMP-2 when compared to the group treated with albendazole alone ''group II'', the differences were found to be statistically significant [p<0.05]. At the same time, the differences in the previously mentioned parameters were proved to be non significant statistically between group V and group VI. There was also a decrease in staining intensity of collagen type IV and fibronectin in groups received the antifibrotics[groups III to VI] in comparison to both groups I and II and the, there was a statistical positive correlation between hydroxyproline biochemical mean value and staining intensity [p<0.05]. Addition of antifibrotic drugs [alpha- chymotrypsin and colchicine] as adjuvant therapy to antiparasitic drugs in treatment of muscular trichinellosis could be a beneficial measure to improve treatment outcome by decreasing both numbers of larvae in the muscle, and fibrous tissue formation, which form together the backbone of pathology and crippling to the patient
ABSTRACT
Objectives: The study aimed to evaluate the benefits of combined therapeutic strategy of multidisciplinary mechanisms in management of cases subjected to chronic hepatic insult inducing fatigue. They were co-linked to perturbations of immune, metabolic and hepatotoxic environmental stress-induced factors posed by cigarette smoking in subjects with Schistosomal hepatic fibrosis infected with hepatitis E [HEV] and/or of chronic hepatitis B [HBV] co-infection. Study Design Selected cases involved fifty cigarette smoker subjects with schistosomal hepatic fibrosis suffering from fatigue symptoms they included twenty five cases with HEV who were categorized into those with history of chronic HBV [Gr. Ia] or without [Gr. IIa] and 25 allied subjects without HEV with of either chronic HBV [Gr, IIIa] or recurrent schisosomal infection [Gr. IVa]. Control group [Gr. V] composed of 10 healthy nonsmokers were also included. The provided therapeutic regimen for 6 months had included ginko bilopa, ginsing, royal jelly, echinacea extracts and sylimarin. The subjects prior to therapy involved [Gr. Ia - Gr. IVa] and post therapeutically [Gr. Ib - Gr. IVb]
Results: Evaluated therapeutic outcome identified significant variation in perturbed biochemical parameters assessed prior to therapy. These included alterations in serum levels of cotinine, protein C, protein S. thrombin -antithrombin complex, thrombomodulin, sialic acid, c-reactive protein, interleukin 6, p-selectin, vitamin E in LDL, vitamin C, hepatocyte growth factor, lipoprotein lipase, lipoprotein a, lipid peroxidation product, asymmetric dimethylarginine [ADMA]
Conclusion: Beneficial outcome was attained by combined multi-disciplinary therapeutic strategy alleviating variable stress-induced factors perpetuating chronic fatigue in subjects with hepatic disposition induced by environmental factors
Recommendations: Environmental factors including cigarette smoking and viral hepatitis [HEV and/or HBV co-infection] imposed in subjects with schistosomal fibrosis stress-induced symptoms of fatigue which may be co-linked to hepatotoxic insult. This could be carefully targeted by combined drug therapy influencing haemostatic immune and metabolic pathways and antioxidant defense mechanisms in subjects with hepatic disposition affecting bio-energetic capacity