No abstract

Abstract. Human Taenia solium cysticercosis is a major cause of epilepsy in developing countries, and porcine infection causes widespread economic losses because of infested pork. Recently, the use of oxfendazole (OFZ) for porcine cysticercosis provided, for the first time, an effective, single-dose treatment. We performed a controlled study to determine the time required between treatment with a single dose of OFZ and the death of cysticerci to define its applicability as preslaughter treatment or as a field control measure. Twenty naturally infected pigs were included in this study. Sixteen received a single dose (30 mg/kg) of OFZ, and were killed in groups of four at one, two, four, and 12 weeks after treatment. Four untreated controls were killed at week 12. No adverse reactions to OFZ were noted. A clear decrease in viability and number of cysts was evident after the first week after therapy, but even at week 4 some viable cysticerci were found in all samples. Twelve weeks after treatment, all meat appeared clear and only minuscule scars remained, except in one animal that had viable brain cysts. This study confirms the efficacy of a single dose of 30 mg/kg of OFZ for porcine cysticercosis but demonstrates that preslaughter treatment of pigs with OFZ will not be useful in controlling cysticercosis. The inclusion of porcine treatment with OFZ in mass cysticercosis control programs is, however, highly promising because it is a simple, effective, inexpensive, and potentially sustainable method for decreasing the porcine reservoir of cysticercosis in disease-endemic countries.

Taenia solium cysticercosis is an important public health problem in developing countries. Oxfendazole has been shown to be highly effective against porcine cysticercosis, when given as a single dose at 30 mg/kg bodyweight. This dose, however, was estimated from experience with albendazole. A controlled dose-response trial was therefore undertaken to determine the efficacy and safety of three concentrations of oxfendazole. Twenty-four naturally parasitised pigs were divided into four groups and treated with oxfendazole at 10 mg/kg, 20 mg/kg or 30 mg/kg, or left untreated. Eight to 10 weeks later the pigs were killed and the viability of the parasites assessed by evagination. No side-effects of oxfendazole treatment were observed. In the control group more than 90 per cent of the cysts were viable. Viable cysts were found in the muscle and brain of the pigs treated with 10 or 20 mg/kg oxfendazole. At 30 mg/kg there were no viable cysts in any of the tissues examined, indicating that this concentration of oxfendazole provided an effective treatment against porcine cysticercosis.

There is a well-established association between aging and the onset of metastasis. Although the mechanisms through which age impinges upon the malignant phenotype remain uncharacterized, the role of a senescent microenvironment has been emphasized. We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state.

Fanconi anemia (FA) patients have an increased risk of acute GVHD (aGVHD) after hematopoietic SCT, with hypersensitivity to DNAcross-linking agents and defective DNA repair. MicroRNA-34 and p53 can induce apoptosis after DNA damage.Here we assessed epithelial cell apoptosis, and studied TP53 and miR-34a expression in the skin and gut biopsies in five non-transplanted FA patients, in 20 FA patients with aGVHD and in 25 acquired aplastic anemia patients (AA). Epithelial apoptosis was higher in FA than in acquired AA patients in both the skin and gut biopsies, though they had a similar preparative regimen. Further study on gut biopsies in FA patients showed that this deleterious effect was not linked to TP53 gene overexpression. As, among p53-independent signaling pathways of apoptosis, the microRNA-34 family mimics p53 apoptotic effects in response to DNA damage, we studied miR-34a expression in the same series of FA patients' gut biopsies. MiR-34a expression level was higher in severe aGVHD compared with non-aGVHD subjects or non-transplanted patients, and significantly related to apoptotic cell numbers across the three groups of FA patients. Thus, in FA patients, increased apoptosis occurs in target epithelial cells of severe aGVHD, and this deleterious effect is linked to overexpression of miR-34a but not TP53.