No abstract

No abstract

No abstract

No abstract

No abstract

BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2–3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian–Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.

MicroRNAs (miRNAs) play regulatory roles in several diseases. In schistosomiasis, the main pathological changes are caused by the granulomatous reaction induced by egg deposition. We aimed to study the changes in host miRNA-223 and miRNA-146b expression in relation to egg deposition and development of hepatic pathology in murine schistosomiasis mansoni. Blood and liver tissue samples were collected from non-infected mice (group I), S. mansoni–infected mice at the 4th, 8th, and 12th weeks post-infection (p.i.) (groups II–IV), and 4 weeks after praziquantel treatment (group V). The collected samples were processed for RNA extraction, reverse transcription, and real-time PCR analysis of miRNA-223 and miRNA-146b. miRNAs’ relative expression was estimated by the ΔΔCt method. Liver tissue samples were examined for egg count estimation and histopathological evaluation. Results revealed that miRNA-223 was significantly downregulated in liver tissues 8 and 12 weeks p.i., whereas miRNA-146b expression increased gradually with the progression of infection with a significantly higher level at week 12 p.i. compared to week 4 p.i. Serum expression levels nearly followed the same pattern as the tissue levels. The dysregulated expression of miRNAs correlated with liver egg counts and was more obvious with the demonstration of chronic granulomas, fibrous transformation, and distorted hepatic architecture 12 weeks p.i. Restoration of normal expression levels was observed 4 weeks after treatment. Collectively, these findings provide new insights for in-depth understanding of host-parasite interaction in schistosomiasis and pave a new way for monitoring the progress of hepatic pathology before and after treatment.