Browsing by Author "Silva, R."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- In vitro neurotoxicity evaluation of piperazine designer drugs in differentiated human neuroblastoma SH-SY5Y cellsPublication . Arbo, M.D.; Silva, R.; Barbosa, D.J.; da Silva, D. Dias; Silva, S.P.; Teixeira, João Paulo; Bastos, M.L.; Carmo, H.Abuse of synthetic drugs is widespread worldwide. Studies indicate that piperazine designer drugs act as substrates at dopaminergic and serotonergic receptors and/or transporters in the brain. This work aimed to investigate the cytotoxicity of N-benzylpiperazine, 1-(3-trifluoromethylphenyl)piperazine, 1-(4-methoxyphenyl)piperazine and 1-(3,4-methylenedioxybenzyl)piperazine in the differentiated human neuroblastoma SH-SY5Y cell line. Cytotoxicity was evaluated after 24 h incubations through the MTT reduction and neutral red uptake assays. Oxidative stress (reactive oxygen and nitrogen species production and glutathione content) and energetic (ATP content) parameters, as well as intracellular Ca(2+) , mitochondrial membrane potential, DNA damage (comet assay) and cell death mode were also evaluated. Complete cytotoxicity curves were obtained after 24 h incubations with each drug. A significant decrease in intracellular total glutathione content was noted for all the tested drugs. All drugs caused a significant increase of intracellular free Ca(2+) levels, accompanied by mitochondrial hyperpolarization. However, ATP levels remained unchanged. The investigation of cell death mode revealed a predominance of early apoptotic cells. No genotoxicity was found in the comet assay. Among the tested drugs, 1-(3-trifluoromethylphenyl)piperazine was the most cytotoxic. Overall, piperazine designer drugs are potentially neurotoxic, supporting concerns on risks associated with the abuse of these drugs. Copyright © 2015 John Wiley & Sons, Ltd.
- Monitoring and molecular profiling of contemporary insecticide resistance status of malaria vectors in Guinea-BissauPublication . Silva, R.; Mavridis, K.; Vontas, J.; Rodrigues, A.; Osório, H.Despite reduction in the prevalence of malaria, Guinea-Bissau (GB) is still widely affected by the disease that is primarily vectored by Anopheles gambiae s.l. mosquitoes. Monitoring mosquito susceptibility and investigating the insecticide resistance status is an integral part of malaria control actions. Here, mosquito populations from five regions of GB: Bafatá, Bissau, Buba, Cacheu and Gabu were monitored for species ID and insecticide resistance, using diagnostic and intensity WHO bioassays, as well as molecular assays. Phenotypic and molecular identification of species showed the presence of An. gambiae s.s. (S form), An. coluzzii (M form) and An. arabiensis, as well as rare An. arabiensis/ An. gambiae hybrids. Resistance to permethrin and deltamethrin was found in all Anopheles populations assayed, with the intensity of resistance for permethrin being moderate to high, as confirmed by bioassays performed at concentration intensities of 5X and 10X. Consistent to these findings, molecular analysis showed a higher frequency of knock-down resistance (kdr) mutations (L1014F, L1014S, reaching > 90% in some areas) compared to previous studies in the same region, as well as detected for the first time the presence of the super kdr mutation (N1575Y) in GB. The “iAche” (G119S) resistance mutation was also found in GB in low frequencies (up to 12.41%). Additionally, the synergistic PBO-permethrin bioassays suggested partial involvement of non target (metabolic and/or reduced penetration) resistance mechanism. Expression analysis of known pyrethroid metabolisers indicated the slight overexpression and possible association of the cytochrome P450s CYP6Z1, CYP4G16 with the pyrethroid resistance phenotype. The findings should guide future evidence-based resistance management strategies in GB.
- Prevalence and molecular characterization of human T cell leukemia virus type 2 in a group of intravenous drug users coinfected with HIV type 1 in PortugalPublication . Silva, A.F.; Almeida, C.; Cortes Martins, H.; Coutinho, R.; Leitão, E.; Silva, R.; Paixão, M.T.; Pádua, E.Human T cell lymphotropic virus type 2 infections can be found in the large urban areas of the United States and Europe, where Spain and Italy are the most affected countries. The population most affected by the epidemic is characterized by high-risk behavior groups, mainly the sharing of needles between intravenous drug users (IDUs) with contaminated cellular blood products. It is also described that HTLV-2 infection appears as a coinfection with HIV-1. We have selected samples corresponding to 583 IDUs infected with HIV and screened for the presence of HTLV-1/2 antibodies. We have performed the molecular characterization of HTLV-2 in three confirmed positive cases on the basis of the long terminal repeat region. We can observe the Portuguese sequences (PortHl, PortNn, and PortVs) in the HTLV-2b cluster, grouping with the Spanish sequences, showing close phylogenetic relatedness. We may assume that HTLV-2 infection was introduced in Portugal from Spain. These results update previous reports that mentioned Portugal as being free of HTLV- 2 infections, and allow the identification of the subtype that is present, giving a first-hand description of the prevalence of HTLV-2 infection in a particular high-risk behavior group and justifying the importance of epidemiological surveillance in order to prevent dissemination of the infection.