Feasibility and efficacy of 223Ra-dichloride (223Ra) to treat bone metastases in patients (pts) with castration resistant prostate cancer (mCRPC)

Aim: To share the Tuscany single-centre experience about the employing of the novel therapeutic radiopharmaceutical 223Ra in the treatment planning of mCRPC pts

Insecticide susceptibility status of Phlebotomus (Paraphlebotomus) sergenti and Phlebotomus (Phlebotomus) papatasi in endemic foci of cutaneous leishmaniasis in Morocco

<p>Abstract</p> <p>Background</p> <p>In Morocco, cutaneous leishmaniasis is transmitted by <it>Phlebotomus sergenti </it>and <it>Ph. papatasi</it>. Vector control is mainly based on environmental management but indoor residual spraying with synthetic pyrethroids is applied in many foci of <it>Leishmania tropica</it>. However, the levels and distribution of sandfly susceptibility to insecticides currently used has not been studied yet. Hence, this study was undertaken to establish the susceptibility status of <it>Ph. sergenti </it>and <it>Ph. papatasi </it>to lambdacyhalothrin, DDT and malathion.</p> <p>Methods</p> <p>The insecticide susceptibility status of <it>Ph. sergenti </it>and <it>Ph. papatasi </it>was assessed during 2011, following the standard WHO technique based on discriminating dosage. A series of twenty-five susceptibility tests were carried out on wild populations of <it>Ph. sergenti </it>and <it>Ph. papatasi </it>collected by CDC light traps from seven villages in six different provinces. Knockdown rates (KDT) were noted at 5 min intervals during the exposure to DDT and to lambdacyhalothrin. After one hour of exposure, sandflies were transferred to the observation tubes for 24 hours. After this period, mortality rate was calculated. Data were analyzed by Probit analysis program to determine the knockdown time 50% and 90% (KDT50 and KDT90) values.</p> <p>Results</p> <p>Study results showed that <it>Ph.sergenti </it>and <it>Ph. papatasi </it>were susceptible to all insecticides tested. Comparison of KDT values showed a clear difference between the insecticide knockdown effect in studied villages. This effect was lower in areas subject to high selective public health insecticide pressure in the framework of malaria or leishmaniasis control.</p> <p>Conclusion</p> <p><it>Phlebotomus sergenti </it>and <it>Ph. papatasi </it>are susceptible to the insecticides tested in the seven studied villages but they showed a low knockdown effect in Azilal, Chichaoua and Settat. Therefore, a study of insecticide susceptibility of these vectors in other foci of leishmaniasis is recommended and the level of their susceptibility should be regularly monitored.</p

Deltamethrin Resistance Mechanisms in Aedes aegypti Populations from Three French Overseas Territories Worldwide

BACKGROUND:Aedes aegypti is a cosmopolite mosquito, vector of arboviruses. The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids, the major class of insecticide used for vector control. French overseas territories such as French Guiana (South America), Guadeloupe islands (Lesser Antilles) as well as New Caledonia (Pacific Ocean), have encountered such resistance. METHODOLOGY/PRINCIPAL FINDINGS:We initiated a research program on the pyrethroid resistance in French Guiana, Guadeloupe and New Caledonia. Aedes aegypti populations were tested for their deltamethrin resistance level then screened by an improved microarray developed to specifically study metabolic resistance mechanisms. Cytochrome P450 genes were implicated in conferring resistance. CYP6BB2, CYP6M11, CYP6N12, CYP9J9, CYP9J10 and CCE3 genes were upregulated in the resistant populations and were common to other populations at a regional scale. The implication of these genes in resistance phenomenon is therefore strongly suggested. Other genes from detoxification pathways were also differentially regulated. Screening for target site mutations on the voltage-gated sodium channel gene demonstrated the presence of I1016 and C1534. CONCLUSION /SIGNIFICANCE:This study highlighted the presence of a common set of differentially up-regulated detoxifying genes, mainly cytochrome P450 genes in all three populations. GUA and GUY populations shared a higher number of those genes compared to CAL. Two kdr mutations well known to be associated to pyrethroid resistance were also detected in those two populations but not in CAL. Different selective pressures and genetic backgrounds can explain such differences. These results are also compared with those obtained from other parts of the world and are discussed in the context of integrative research on vector competence

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

Visceral leishmaniasis is a vector-borne disease characterized by fever, spleen and liver enlargement, and low blood cell counts. In the Americas VL is zoonotic, with domestic dogs as main animal reservoirs, and is caused by the intracellular parasite Leishmania infantum (syn. Leishmania chagasi). Humans acquire the infection through the bite of an infected sand fly. The disease is potentially lethal if untreated. VL is reported from Mexico to Argentina, with recent trends showing a rapid spread in Brazil. Control measures directed against the canine reservoir and insect vectors have been unsuccessful, and early detection and treatment of human cases remains as the most important strategy to reduce case fatality. Well-designed studies evaluating diagnosis, treatment, and prevention/control interventions are scarce. The available scientific evidence reasonably supports the use of rapid diagnostic tests for the diagnosis of human disease. Properly designed randomized controlled trials following good clinical practices are needed to inform drug policy. Routine control strategies against the canine reservoirs and insect vectors are based on weak and conflicting evidence, and vector control strategies and vaccine development should constitute research priorities

Decimated Wavelet Representation of Images – Application to Compression

A new way to improve the representation of images using a discrete wavelet transform for coding purposes is presented. The idea lies in combining all wavelet coefficients related to detail information at a same resolution level but along different orientations (horizontal, vertical, and diagonal), into a single image. Given that detail information is located for all subband images in the neighborhood of high frequency textures or edge locations, the pattern of significant coefficients remains unchanged after the combination process. This process allows one to further reduce the number of transformed coefficients by 2/3, while preserving the multiresolution structure. This information can thus be efficiently coded using a multiresolution embedded coding scheme, such as Shapiro's (see IEEE Trans. on Signal Proc., vol.SP-41, no.12, p.3445-62, 1993) zerotree coder. Overall, a higher coding efficiency can be reached while preserving the cross-scale prediction of significance among the coefficients. Ultimately, approximate detail information must be recovered from the combined and coded data for each subband of the original wavelet, so as to reconstruct a decoded imag

Novel radiopharmaceuticals for therapy

In the era of personalizedmedicine, "target radionuclide therapy" (TRT) is designed to damage only the cancerous cells while sparing unnecessary damage to the adjacent healthy cells/tissues. Unlike conventional external beam radiation therapy, TRT is intended to cause less or no collateral damage to normal tissues, as it aims at achieving targeted drug delivery either to a clinically diagnosed cancer not amenable to surgery or to metastatic tumor cells and tumor cell clusters, thus providing systemic therapy of cancer. Currently there are hundreds of new pathwaytargeted anticancer agents undergoing phase II and phase III clinical trials. TRT is just one type within the domain of "targeted therapies." In addition to the effective targeted radiopharmaceuticals already well validated for routine clinical use, newer radiolabeled agents are still in the phase of either preclinical or clinical validation. This chapter describes the main physical and radiochemical characteristics of radionuclides that have potential or have already been employed to label biologically reactive molecules for the development of novel radiopharmaceuticals for therapy. Some of these agents have entered advanced clinical trials in tumor-bearing patients. Results of these clinical trials cover a wide spectrum of potential clinical usefulness. The chapter is divided into two main parts depending on the type of particle emission (α- or β-associated or not with the emission of either γ- or β+-radiation). Within each domain, there is some exchange of experience and shift of focus in the various phases of development, depending on the modalities of ascertaining efficient tumor targeting according to the principles of theranostics. The example of a novel α-emitting radiopharmaceutical that has most recently achieved approval by regulatory agencies for clinical use ( 223 Ra-dichloride) is presented in detail as the paradigm for an agent that is showing a survival advantage besides the original target of pain palliation from bone metastases