Homeopathic medicines cause Th1 predominance and induce spleen and megakaryocytes changes in BALB/c mice infected with Leishmania infantum.

The prevalence of Th1/Th2 response, spleen changes and megakaryocytes were investigated in BALB/c mice (n=138) infected with Leishmania infantum, and treated with Leishmania infantum 30× (10-30) biotherapy - BioLi30×. We performed controlled experiments using 8-to-12-week-old mice, infected with 5×107L. infantum promastigotes, divided into eight groups: G1 (healthy), G2 (infected with L. infantum), G3 (BioLi30× pre-treated), G4 (BioLi30× pre/post-treated), G5 (BioLi30× post-treated), G6 (Water 30× post-treated), G7 (Antimonium crudum 30× post-treated) and G8 (Glucantime® post-treated). G3-G7 groups were orally treated with their respective drugs diluted in filtered water (1:10), and G8 received Glucantime® (0.6mg/100µl of PBS), intraperitoneally. Spleen fragments were submitted to double blind histopathological evaluation and the number of megakaryocytes was counted. Besides, animals' serum was measured after 49days of infection, and cytokines (IFN-γ, IL-4, IL-10, IL-12), as well as the Th1/Th2 correlation (IFN-γ/IL-4 and IFN-γ/IL-10), were analyzed. Spleen histological parameters were classified as: healthy appearance (G1); discreet (G3-G7), moderate (G2) and moderate to severe (G8) white pulp hyperplasia; proliferation of megakaryocytes (G2-G8), and intense disruption (G2-G8). All groups, except for G7, showed higher percentages of megakaryocytes per field ranging from 87% to 15%, when compared to healthy animals (G1). Th1 predominance in IFN-γ/IL-4 ratio (comparing to G2) was detected in G4, G5, G6 and G7. Finally, pre/post (BioLi30x) and post-treatment (Antimonium crudum 30x) presented reduction of megakaryocytes/spleen changes due to immunomodulation animal process, controlling the infection process, probably by the Th1 cytokine predominance.

Silymarin reduces profibrogenic cytokines and reverses hepatic fibrosis in chronic murine schistosomiasis.

In chronic schistosomiasis, hepatic fibrosis is linked to the portal hypertension that causes morbidity in Schistosoma mansoni infection. Silymarin (SIL) is a hepatoprotective and antioxidant medicament largely prescribed against liver diseases that has previously been shown to prevent fibrosis during acute murine schistosomiasis. Here we employed silymarin to try to reverse established hepatic fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to BALB/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50 days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma sizes, reduced the increase in alanine aminotransferase and aspartate aminotransferase levels, and reduced the established hepatic fibrosis (assessed by hydroxyproline contents and picrosirius staining). Treatment with silymarin also reduced the levels of interleukin-13 (IL-13) in serum and increased the gamma interferon (IFN-γ)/IL-13 ratio. There was a linear correlation between IL-13 levels in serum and hydroxyproline hepatic content in both infected untreated and SIL-treated mice, with decreased IL-13 levels corresponding to decreased hydroxyproline hepatic contents. Treatment with either SIL or N-acetylcysteine reduced both proliferation of fibroblast cell lines and basal/IL-13-induced production of collagen I, indicating that besides inhibiting IL-13 production during infection, SIL antioxidant properties most likely contribute to inhibition of collagen production downstream of IL-13. These results show that silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a safe and cheap treatment to liver fibrotic disease in schistosomiasis.

In vitro and in vivo influence of penetration enhancers in the topical application of celecoxib.

OBJECTIVE: We investigated the potential effects of oleic acid (OA) and glycerol monooleate (GMO) on the skin delivery of CXB. METHODS: The influence of both OA and GMO (5.0% or 10.0%) on the in vitro skin permeability of CXB (2.0%) was evaluated using propylene glycol (PG) as a vehicle. Also the in vitro potential cytotoxicity and genotoxicity and in vivo assays (skin irritation in rabbits and topical anti-inflammatory activity by in mice) were conducted. RESULTS: As expected, the amount of CXB that permeated through the skin was minimal, but drug retention on the viable skin (epidermis plus dermis) was higher in association with treatment with 5.0% OA or GMO compared to the control treatment, meaning that there was a localized effect of CXB in the skin. No formulation presented cytotoxic or genotoxic potential, suggesting safety for cutaneous application. In vivo skin irritation assays indicated that no formulation was irritating to the skin becomes its use possible for a prolonged time. In vivo anti-inflammatory experiments indicated that both edema and protein extravasation were inhibited with a maximum % inhibition of 53.5.0% and 61.0% for 5.0 % GMO, respectively, and 48.0% and 35.5% for 5.0% OA, respectively. Such formulations were able to inhibit around twofold the percentage of ear edema in mice compared to a commercial product reference diclofenac commercial formula. CONCLUSION: There is no topical formulation currently available that contains both CXB and 5.0% GMO or OA, suggesting them as potential adjuvants that improve the skin delivery of CXB.

Interaction and involvement of cellular adhesion molecules in the pathogenesis of Schistosomiasis mansoni.

Parasites from genus Schistosoma currently infect more than 200 million people worldwide. Infection with Schistosoma mansoni causes intestinal schistosomiasis with geographical distribution across Africa, Middle East, Caribbean, Brazil, Venezuela and Suriname. People with Schistosomiasis mansoni suffer from a chronic disease as result of an exacerbated immune response to the eggs deposited in hepatic tissue. The presence of eggs in the tissue triggers the recruitment and activation of immune cells to wall off and isolate them from the rest of the organism. In this context, immune cells turn activated and increase the expression of cellular adhesion molecules (CAM), such as l-selectin and LFA-1, and DC-SIGN which through interaction with CAM expressed on activated endothelial vessels, help moving leukocytes quickly to the sites of infection (inflammation around the eggs), as a strategy to defend the organism from foreign invaders. Since the vertebrate host is not able to eliminate the foreign invader a granuloma formation take place in the tissue where the eggs are trapped, originating granulomas. Patients and mice with chronic schistosomiasis have increased levels of CAM in their circulation and egg-trapped tissue, which may contribute to the inflammatory process, granuloma formation and pathology aggravation. Here we systematically reviewed the findings raised over the last two decades that addressed the involvement of cellular adhesion molecules in the intestinal and hepatic inflammatory response and liver granuloma formation during Schistosomiasis mansoni. This review intends to contribute to the understanding of Schistosomiasis mansoni pathogenesis by discussing alterations and interactions in cellular adhesion molecules during the disease.

Meglumine-based supra-amphiphile self-assembled in water as a skin drug delivery system: Influence of unfrozen bound water in the system bioadhesiveness.

Hexagonal liquid crystals and supramolecular polymers from meglumine-based supra-amphiphiles were developed as drug delivery systems to be applied on the skin. The influence of fatty acid unsaturation on the structure and mechanical properties was evaluated. Moreover, we have investigated the system biocompatibility and how the type of water could influence its bioadhesive properties. Meglumine-oleic acid (MEG-OA) was arranged as hexagonal liquid crystals at 30-70 wt% water content, probably due to its curvature and increased water solubility. Meglumine-stearic acid (MEG-SA) at 10-80 wt% water content self-assembled as a lamellar polymeric network, which can be explained by the low mobility of MEG-SA in water due to hydrophobic interactions between fatty acid chains and H-bonds between meglumine and water molecules. Both systems have shown suitable mechanical parameters and biocompatibility, making them potential candidates to encapsulate therapeutic molecules for skin delivery. Moreover, a strong positive correlation between the amount of unfrozen bound water in meglumine-based systems and the bioadhesion properties was observed. This work shows that a better understanding of the physicochemical properties of a drug delivery system is extremely important for the correlation with the desired biological response and, thus, improve the product performance for biomedical applications.