Diagnóstico molecular da alteração mutagênica nt 230 (del4) no gene MDR1 em cães

P-glycoprotein is an adenosine triphosphate (ATP)-driven drug efflux carrier responsible for transport of xenobiotics and multiple classes of drugs, many usually use in veterinary medicine. Encoded by MDR1 gene, also referred to as ABCB1, located on chromosome 14, is expressed in many tissues with secretory or excretory functions, such as liver, kidney and intestine, where it limits drug absorption from the gut and promotes drug excretion into the bile and urine of their substrates. In 2001, a 4 base pair gene deletion mutation in the canine MDR1 gene was identified as MDR1-1▲, ABCB1-1▲, MDR1 MDR1 nt 230 (del4) and associated with an non-functional Pglycoprotein. The clinical correlation is the (hyper) sensitivity of certain dogs breeds, mostly collies, to a few classes of drugs such as anticancer drugs (doxorubicin, vincristine, vinblastine), immunosuppressants (cyclosporine), antiparasitic drugs (ivermectin, moxidectin), steroids hormones (aldosterone, cortisol, dexamethasone), antimicrobial agents (tetracycline, doxycycline, levofloxacin, ketoconazole, itraconazole), analgesics (morphine, methadone), antidiarrheals (loperamide), antiepileptic agents (phenothiazine), cardiac drugs (digoxin, diltiazem, verapamil, talinolol) and others. Dogs with homozygous MDR1 nt 230 (del4) MDR1 mutations (MDR1 - / -) have a higher predisposition to intoxication with substrates of P-gp than heterozygous (MDR1 + / -) and these are more likely than dogs homozygous nonmutant (MDR1 +/ +). After the identification of nt230 (del4) mutation, several molecular techniques have been developed for identification of mutant animals as a diagnostic method. The importance of molecular diagnosis is, after the identification of mutant animals, establish treatment protocols safe, exclude this animals from reproduction (genetic selection program) and investigating the history of adverse drugs reactions... (Complete abstract click electronic access below)

Aspectos clínicos e cirúrgicos do osteossarcoma canino

Osteosarcoma is the primary osseous neoplasia frequently diagnosed in dogs and it’s the main answerable for more than 85% of the neoplasias origened from the skeleton. The average age of onset of the lesion is 7 years, especially in large breeds and giant, with males being more affected than females. In general, 75% of osteosarcomas develop in the appendicular skeleton and 25% in the axial. The forelimbs are more affected than the hindlimbs, since support 60% of body weight. The osteosarcoma diagnosis is made by the analys of the animal’s clinic historic, detailed physique exams, blood exams alkaline phosphatase, xray exams, cytology, biopsy. The treatment of choice is the amputation associated to the chemotherapy. However, in some cases the member is preserved by the allograft technic. The chemotherapy associated to the surgery reduces the total load of the tumor, lengthens the interval of the life and improves the quality of pacient’s life. The most used medicines are cisplatin and doxorubicin. They can be used in separated or associated ways. The prognostic of dogs with osteosarcoma is reserved

Remodelamento do miocárdio na cardiomiopatia dilatada induzida com doxorrubicina em coelhos

Pós-graduação em Medicina Veterinária - FCAV

Metaloproteinases da matriz 2 e 9 em coelhos com cardiomiopatia induzida pela doxorrubicina

Pós-graduação em Medicina Veterinária - FCAV

Síntese e estudos de sistemas de bioencapsulação associados a peptídeos antimicrobianos miméticos da toxina natural CcdB

Pós-graduação em Biotecnologia - IQ

Toxicidade do cloridrato de doxorrubicina na dose de 120mg/m², em cadelas com tumor venéreo transmissível

Pós-graduação em Cirurgia Veterinária - FCAV

Tumor mamário canino: estudo in vitro, imunomarcação e ação da doxorrubicina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Multi-walled carbon nanotubes modified screen-printed electrodes for cisplatin detection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Challenges in the therapy of visceral leishmaniasis in Brazil: a public health perspective

Over 3,000 yearly cases of Visceral Leishmaniasis (VL) are reported in Brazil. Brazilian Public Health System provides universal free access to antileishmania therapeutic options: Meglumine Antimoniate, Amphotericin B deoxycholate, and Liposomal Amphotericin B. Even though Amphotericin formulations have been advised for severe disease, this recommendation is mostly based on the opinion of experts and on analogy with studies conducted in other countries. Presently, there are two ongoing multicenter clinical trials comparing the efficacy and safety of the available therapeutic options. Some other issues require further clarification, such as severity markers and the approach to VL/AIDS coinfection. Brazil is facing the challenge of providing access to diagnosis and adequate treatment, in order to avoid VL-related deaths.

Effectiveness of hyperbaric oxygen for experimental treatment of schistosomiasis mansoni using praziquantel-free and encapsulated into liposomes: Assay in adult worms and oviposition

The treatment of schistosomiasis depends on a single drug: praziquantel (PZQ). However, this treatment presents limitations such as low and/or erratic bioavailability that can contribute to cases of tolerance. Improvements to the available drug are urgently needed and studies with a controlled system of drug release, like liposomes, have been gaining prominence. The present study evaluated the activity and synergy between liposomal-praziquantel (lip.PZQ) and hyperbaric oxygen therapy (HBO). Mice received doses of 60 or 100mg/kg PZQ or lip.PZQ, 50 days post-infection, and after the treatment, were exposed to HBO (3 atmosphere absolute - ATA) for 1h. The viability of adult worms and oviposition were analyzed, by necropsy and Kato-Katz examination performed after 15 days of treatment. A concentration of 100mg/kg of lip.PZQ+HBO was more effective (48.0% reduction of worms, 83.3% reduction of eggs/gram of feces) and 100% of the mice had altered of oograms (indicating interruption of oviposition) compared to other treatments and to the Control group (infected and untreated). It is known that PZQ requires participation of the host immune system to complete its antischistosomal activity and that HBO is able to stimulate the immune system. The drug became more available in the body when incorporated into liposomes and, used with HBO, the HBO worked as an adjuvant. This explains the decreases of oviposition and worms recovered form hepatic portal system.

Antiproliferative activity of cardenolide glycosides from Asclepias subulata

Asclepias subulata Decne. is a shrub occurring in Sonora-Arizona desert (Mexico-USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata. A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3-O-glucopyranoside had IC50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata, and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds.

Efeitos das formulações nanoestruturadas de doxorrubicina e cisplatina em dispersão de óxido de grafeno reduzido no tratamento da progressão do câncer de bexiga Não-músculo invasivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência do extrato de chá verde na remodelação cardíaca induzida por administração de doxorrubicina

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Perfil tóxico-farmacológico da administração da doxorrubicina em cães com tumor venéreo transmissível

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)