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1.
Bioinorg Chem Appl ; 2024: 1018375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601021

RESUMO

Nowadays, the search for new chemotherapeutic agents with low toxicity and high selectivity is a major concern. In this paper, we report the synthesis and characterization of a hybrid thiosemicarbazone/hydrazone ligand in its neutral form (L1H2) and as the chloride salt ([L1H3]Cl)-, three diorganotin (IV) complexes, and one complex with Sn (IV). The compounds have been fully characterized by IR, mass spectra, 1H, 13C, and 119Sn NMR, 119Sn CP/MAS NMR, and by single crystal X-ray diffraction. The organotin compounds have the empirical formula [SnR2L1] (R = Me, Bu, and Ph), but in the solid state, they are polymeric species with seven coordination number due to weak coordination of the pyridine nitrogen, whereas in solution, the polymeric structure is lost to afford hexacoordinate monomeric species. Reaction with SnI4 yields complex [Sn (L1)2]·EtOH, with the metal in a distorted dodecahedral arrangement. We have evaluated the antiproliferative activity of the two forms of the ligands and the four coordination compounds against MDA-MB-231, HeLa, PC3, and HepG2 cancer cell lines, and WI-38 normal cell line, and all the compounds present higher activity than cisplatin, used as the standard control. To investigate the mode of action, we have selected the most active complex, containing phenyl substituents, and used the triple negative breast cancer cell line MDA-MB-231. The results show that the complex induces apoptotic cell death promoted by generation of reactive oxygen species and by disruption of mitochondrial membrane potential.

2.
Clin. transl. oncol. (Print) ; 23(3): 536-542, mar. 2021.
Artigo em Inglês | IBECS | ID: ibc-220888

RESUMO

Purpose Treatment of recurrent ovarian carcinoma is a challenge, particularly for the clear cell (CCC) subtype. However, there is a preclinical rationale that these patients could achieve a benefit from antiangiogenic therapy. To assess this hypothesis, we used the growth modulation index (GMI), which represents an intrapatient comparison of two successive progression-free survival (PFS). Methods We conducted a retrospective real-world study performed on 34 patients with recurrent ovarian cancer, treated with bevacizumab-containing regimens from January 2009 to December 2017. The primary endpoint was GMI. An established cut-off > 1.33 was defined as a sign of drug activity. Results 73.5% of patients had high-grade serous ovarian carcinoma (HGSOC), and 17.7% had CCC; 70.6% of patients received carboplatin/gemcitabine/bevacizumab, and 29.4% received weekly paclitaxel/bevacizumab. According to histological subtype, the overall response rate and median PFS were 52% and 14 months for HGSOC and 83.3% and 20 months for CCC, respectively. The overall population median GMI was 0.99; it was 0.95 and 2.36 for HGSOC and CCC, respectively. CCC subtype was significantly correlated with GMI > 1.33 (odds ratio 41.67; 95% confidence interval 3.6–486.94; p = .03). Conclusion Adding bevacizumab to chemotherapy in recurrent CCC is associated with a remarkable benefit in this cohort. The efficacy of antiangiogenic drugs in CCC warrants further prospective evaluation (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adenocarcinoma de Células Claras/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Bevacizumab/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Recidiva Local de Neoplasia , Resultado do Tratamento
3.
Clin Transl Oncol ; 23(3): 536-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32651885

RESUMO

PURPOSE: Treatment of recurrent ovarian carcinoma is a challenge, particularly for the clear cell (CCC) subtype. However, there is a preclinical rationale that these patients could achieve a benefit from antiangiogenic therapy. To assess this hypothesis, we used the growth modulation index (GMI), which represents an intrapatient comparison of two successive progression-free survival (PFS). METHODS: We conducted a retrospective real-world study performed on 34 patients with recurrent ovarian cancer, treated with bevacizumab-containing regimens from January 2009 to December 2017. The primary endpoint was GMI. An established cut-off > 1.33 was defined as a sign of drug activity. RESULTS: 73.5% of patients had high-grade serous ovarian carcinoma (HGSOC), and 17.7% had CCC; 70.6% of patients received carboplatin/gemcitabine/bevacizumab, and 29.4% received weekly paclitaxel/bevacizumab. According to histological subtype, the overall response rate and median PFS were 52% and 14 months for HGSOC and 83.3% and 20 months for CCC, respectively. The overall population median GMI was 0.99; it was 0.95 and 2.36 for HGSOC and CCC, respectively. CCC subtype was significantly correlated with GMI > 1.33 (odds ratio 41.67; 95% confidence interval 3.6-486.94; p = .03). CONCLUSION: Adding bevacizumab to chemotherapy in recurrent CCC is associated with a remarkable benefit in this cohort. The efficacy of antiangiogenic drugs in CCC warrants further prospective evaluation.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Intervalos de Confiança , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Razão de Chances , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Gencitabina
4.
J Appl Microbiol ; 130(6): 1913-1924, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33151599

RESUMO

AIMS: To analyse the non-glycosylated protein fraction from Melipona beecheii honey for antimicrobial activity against Escherichia coli O157:H7. METHODS AND RESULTS: The proteins from M. beecheii honey were separated according to their degree of glycosylation using Concanavalin A-affinity chromatography. The total protein extract and its fractions were analysed by 1D and 2D electrophoresis. We also determined the antimicrobial and antihaemolytic activities of the total protein extract and the non-glycosylated fraction. Furthermore, we evaluated the effect of this non-glycosylated fraction for the expression of the Stx1, Stx2, EAE and HlyA pathogen genes. Melipona beecheii honey contained at least 24 proteins with molecular weights ranging between 7·6 and 95 kDa and isoelectric points between 3 and 10, three proteins from the 24 are non-glycosylated. The non-glycosylated fraction had an MIC90 of 1·128 µg ml-1 , and this fraction inhibited the haemolytic activity of the pathogen, as well as reduced the expression of Stx1, Stx2 and HlyA. The MbF1-2 protein from the non-glycosylated fraction was sequenced and identified as a homologue of the royal jelly-like protein of Melipona quadrifasciata. CONCLUSIONS: The non-glycosylated protein fraction from M. beecheii honey greatly contributes to antibacterial activity and it is composed of at least three proteins, of which MbF1-2 provided over 50% of the antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study showed significant antimicrobial activity from several proteins present in the honey of M. beecheii. Interestingly, the non-glycosylated protein fraction demonstrated antihaemolytic activity and adversely affected the expression of virulence genes in Escherichia coli O157:H7; these proteins have the potential to be used in developing therapeutic agents against this bacterium.


Assuntos
Antibacterianos/farmacologia , Abelhas/química , Escherichia coli O157/efeitos dos fármacos , Mel , Proteínas de Insetos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Escherichia coli O157/genética , Escherichia coli O157/patogenicidade , Expressão Gênica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Mel/análise , Proteínas de Insetos/química , Proteínas de Insetos/isolamento & purificação , Testes de Sensibilidade Microbiana , Fatores de Virulência/genética
5.
EJC Suppl ; 15: 49-55, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33240442

RESUMO

Cancers develop by sustained growth, migration and invasion properties of tumour cells, supported by complex interactions with stromal cells within the tumour micro-environment. This review is focused on the latest discoveries regarding the highlighted role of angiogenesis and tumour micro-environment in ovarian cancer. This cancer milieu encompasses non-cancerous cells present in the tumour or nearby, including vessel-forming cells, fibroblasts and immune cells amongst others that work in a cooperative way with cancer cells, impacting tumour behaviour. Angiogenesis, migration and invasion, and more recently immune evasion, are cancer hallmarks clearly dependent on these supporting cells. Moreover, these stromal cells are more genetically stable than tumour cells and thus represent an attractive therapeutic target. A better understanding of the stromal cells function, and their complex interplay with cancer cells, will open additional areas to target, as the tumour-host interface.

6.
Clin Transl Oncol ; 22(10): 1849-1856, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32125644

RESUMO

BACKGROUND: Soft tissue sarcomas (STS) have a high risk of relapse in spite of the use of (neo)adjuvant chemotherapy. In this context, looking for new prognostic biomarkers is an interesting field of research. Our aim is to analyze the prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and other serum markers in patients with STS who received chemotherapy with curative intent. MATERIALS AND METHODS: This is a retrospective observational study. We included all patients with STS (primary tumor, local recurrence or resected metastatic disease) treated with high-dose ifosfamide and epirubicin with curative intent from January 2007 to December 2018. The pretreatment NLR and other serum markers were calculated, selecting the median as the cut-off value for the survival and multivariate analysis. RESULTS: Seventy-nine patients were included. Median NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were 2.83, 174.05 and 3.25, respectively. Median progression-free survival (PFS) was significantly longer in patients with low NLR [not reached (NR) vs 21, 92 months, P < 0.01]. No significant differences were found for PFS regarding PLR or LMR. For overall survival (OS), a significant survival advantage was also found for patients with low NLR (NR vs 65.45 months, P = 0.01), without differences for PLR or LMR. In multivariate analysis, NLR remains an independent prognostic factor for PFS. CONCLUSION: In our cohort, low NLR was significantly associated with a longer PFS and OS, and is consolidated as an independent prognostic factor.


Assuntos
Linfócitos , Neutrófilos , Sarcoma/mortalidade , Adolescente , Adulto , Idoso , Plaquetas , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/sangue , Sarcoma/terapia , Adulto Jovem
7.
Eur J Med Chem ; 148: 372-383, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29471123

RESUMO

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ouro/química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiossemicarbazonas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Citotoxinas , Feminino , Humanos , Células MCF-7 , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiossemicarbazonas/farmacologia
8.
Parasite Immunol ; 39(6)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28345149

RESUMO

Trichomonas vaginalis (Tv) is a flagellated parasite commonly spread through sexual transmission. This protozoan initiates a severe inflammatory process, inducing nitric oxide, interleukin-6 (IL-6), IL-8, IL-10, IL-17 and IL-22 production by host immune cells. The parasites elicit these responses by releasing surface lipophosphoglycan, small extracellular vesicles (exosomes) and other factors. Tv exosomes are similar to mammalian exosomes and have been implicated in the modulation of IL-8 secretion by epithelial cells. Here, we report that exosome-like vesicles from T. vaginalis (Tv-ELVs) induced a more than 15-fold increase in IL-10 expression in RAW264.7 macrophages but only a two fold increase in IL-6 and TNF-α expression levels measured by RT-PCR. Because Tv-ELVs modulated the macrophage response, we also explored the effect of Tv-ELVs in a murine model of infection. Pretreatment with Tv-ELVs significantly increased IL-10 production as measured in vaginal washes by days 8 and 16 post-infection. Remarkably, Tv-ELVs-pretreated mice exhibited a decrease in IL-17 production and a significant decrease in vulvar inflammation. In addition, IL-6 and IL-13 were decreased during infection. Our results suggest that Tv-ELVs have an immunomodulatory role on the cytokine profile induced by the parasite and promote a decrease in the inflammatory process in mice infected with T. vaginalis.


Assuntos
Citocinas/metabolismo , Vaginite por Trichomonas/imunologia , Trichomonas vaginalis/imunologia , Animais , Células Epiteliais/imunologia , Exossomos/imunologia , Feminino , Glicoesfingolipídeos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/parasitologia , Ativação de Macrófagos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Células RAW 264.7 , Vulva/imunologia
9.
J Inorg Biochem ; 163: 118-130, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27426049

RESUMO

Four novel ligands derived from 2,3-butanedione have been synthesized, two dissymmetric thiosemicarbazone/3-hydroxy-2-naphthohydrazone ligands, H2L1 (bearing 4-isopropyl-3-thiosemicarbazone) and H2L2 (containing 4-cyclohexyl-3-thiosemicarbazone) and the symmetric H2L3, diacetyl bis(3-hydroxy-2-naphthohydrazone), and H2L4, diacetyl bis(4-cyclohexyl-3-thiosemicarbazone). Their reactivity with SnR2Cl2 (R=methyl, n-butyl and phenyl) was explored and the resulting complexes were characterized by elemental analysis, molar conductivity, mass spectrometry, IR, 1H, 13C and 119Sn NMR and seven of them also by single crystal X-ray diffraction. The results showed that the reactivity of the dissymmetric ligands is strongly different and while the cyclohexyl derivative is very stable, with isopropyl easily undergoes a symmetrization reaction to yield the corresponding symmetric ligands. The antimicrobial activity of the ligands and the corresponding diorganotin(IV) complexes was investigated in vitro against seven species of microorganisms and minimum inhibitory concentrations (MICs) were determined. The results showed that the ligand H2L2 and several of its derivatives, together with methyl and phenyl complexes of H2L1, have the ability of inhibiting the growth of tested bacteria and fungi to different extents. Bacillus subtilis and Staphylococcus aureus Gram positive strains were the most sensitive microorganisms.


Assuntos
Anti-Infecciosos , Bacillus subtilis/crescimento & desenvolvimento , Hidrazonas , Staphylococcus aureus/crescimento & desenvolvimento , Tiossemicarbazonas , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia
10.
Oncogenesis ; 5(7): e244, 2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27454079

RESUMO

Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis.

11.
Lett Appl Microbiol ; 60(6): 517-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25689035

RESUMO

Giardia intestinalis is a pathogen associated with foodborne outbreaks and Escherichia coli is commonly used as a marker of faecal contamination. Implementation of routine identification methods of G. intestinalis is difficult for the analysis of vegetables and the microbiological detection of E. coli requires several days. This study proposes a PCR-based assay for the detection of E. coli and G. intestinalis cysts using crude DNA isolated from artificially contaminated lettuce. The G. intestinalis and E. coli PCR assays targeted the ß-giardin and uidA genes, respectively, and were 100% specific. Forty lettuces from local markets were analysed by both PCR and light microscopy and no cysts were detected, the calculated detection limit was 20 cysts per gram of lettuce; however, by PCR, E. coli was detected in eight of ten randomly selected samples of lettuce. These data highlight the need to validate procedures for routine quality assurance. These PCR-based assays can be employed as alternative methods for the detection of G. intestinalis and E. coli and have the potential to allow for the automation and simultaneous detection of protozoa and bacterial pathogens in multiple samples. Significance and impact of the study: There are few studies for Giardia intestinalis detection in food because methods for its identification are difficult for routine implementation. Here, we developed a PCR-based method as an alternative to the direct observation of cysts in lettuce by light microscopy. Additionally, Escherichia coli was detected by PCR and the sanitary quality of lettuce was evaluated using molecular and standard microbiological methods. Using PCR, the detection probability of Giardia cysts inoculated onto samples of lettuce was improved compared to light microscopy, with the advantage of easy automation. These methods may be employed to perform timely and affordable detection of foodborne pathogens.


Assuntos
Escherichia coli/genética , Contaminação de Alimentos/análise , Giardia lamblia/genética , Lactuca/microbiologia , Lactuca/parasitologia , Cistos , Proteínas do Citoesqueleto/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , DNA de Protozoário/análise , DNA de Protozoário/genética , Fezes/microbiologia , Fezes/parasitologia , Microbiologia de Alimentos/métodos , Parasitologia de Alimentos/métodos , Glucuronidase/genética , Reação em Cadeia da Polimerase/métodos , Proteínas de Protozoários/genética
13.
Rev Clin Esp (Barc) ; 214(7): 379-80, 2014 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25053205
14.
Br J Cancer ; 110(4): 1088-100, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24548884

RESUMO

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Estudos de Casos e Controles , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética
15.
J Eur Acad Dermatol Venereol ; 28(7): 907-14, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23848131

RESUMO

BACKGROUND: There are few data on the prevalence of obesity in the general psoriasis population and on the real impact of obesity on the management of psoriasis patients in the clinical setting. OBJECTIVES: To evaluate the prevalence of overweight and obesity in patients with moderate-to-severe psoriasis compared to the general population and to assess the relationship between Body Mass Index (BMI) and the risk of discontinuing treatment. METHODS: Patients registered on Biobadaderm, a prospective registry, were grouped according the different categories of BMI and compared to the general Spanish population. Drug survival was analysed considering only drug withdrawal due to lack of effectiveness, remission and adverse events. RESULTS: A total of 1162 moderate-to-severe psoriasis patients on systemic conventional or biological treatment were recruited. The prevalence of obesity was found to be significantly higher in psoriasis patients than in the general Spanish population (P < 0.001). In multivariate analysis a 5-unit increase in BMI, similar to a change in BMI category from normal weight to overweight and from overweight to obesity, was associated with a 12% increased risk of discontinuing therapy due to lack of effectiveness (HR 1.12, 95% CI: 1.01-1.24) and with a 17% increased risk of having an adverse event (HR 1.17, 95% CI: 1.02-1.36), both independently of the drug used. CONCLUSIONS: Patients with moderate-to-severe psoriasis had a higher prevalence of obesity than the general population. Increased BMI was associated with an increased risk of treatment discontinuation due to lack of effectiveness and a higher risk of adverse events.


Assuntos
Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Índice de Massa Corporal , Obesidade/complicações , Obesidade/epidemiologia , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Suspensão de Tratamento , Comorbidade , Humanos , Análise Multivariada , Sobrepeso/complicações , Sobrepeso/epidemiologia , Prevalência , Estudos Prospectivos , Psoríase/epidemiologia , Sistema de Registros , Fatores de Risco , Espanha/epidemiologia , Resultado do Tratamento
16.
BJOG ; 120(12): 1534-47, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23924192

RESUMO

OBJECTIVE: To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). DESIGN: Retrospective cohort study. SETTING: Three university medical centers, USA. POPULATION: HIV-infected pregnant women initiated or restarted on HAART during pregnancy. METHODS: We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. MAIN OUTCOME MEASURES: Time to HIV viral load <400 copies/ml and <1000 copies/ml. RESULTS: We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml. CONCLUSIONS: Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1 , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Terapia Diretamente Observada/estatística & dados numéricos , Feminino , Infecções por HIV/virologia , Humanos , Estimativa de Kaplan-Meier , Adesão à Medicação , Gravidez , Complicações Infecciosas na Gravidez/virologia , Trimestres da Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
17.
J Inorg Biochem ; 105(5): 600-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21443849

RESUMO

Several methyltin(IV) and butyltin(IV) complexes with the ligand benzil bis(benzoylhydrazone) and 4,4'-bipyridyl as coligand were synthesised and characterized by elemental analysis and by IR, (1)H, (13)C and (119)Sn NMR spectroscopies. Some of them were also analyzed using single crystal X-ray diffraction. The title compounds were evaluated for their in vitro antimicrobial properties. All buthyltin complexes showed significant inhibition of Gram positive bacteria, resulting Bacillus subtilis, Sarcina lutea and both methicillin-susceptible and methicillin-resistant Staphylococcus epidermidis the most sensitive strains. Furthermore, they were able to inhibit the growth of Gram negative bacteria, especially Proteus vulgaris, whereas no activity was exhibited against fungi. All methyltin complexes were devoid of antimicrobial properties.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Hidrazonas/química , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/síntese química , Piridinas/química , Anti-Infecciosos/síntese química , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Ligantes , Testes de Sensibilidade Microbiana , Compostos Orgânicos de Estanho/farmacologia
18.
Gynecol Oncol ; 118(1): 88-92, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20439111

RESUMO

Ovarian cancer is the second most common gynecologic malignancy, and represents the fifth most common cause of cancer death in women in the United States. The age at diagnosis, extent of disease, success of primary surgery, and the histopathological features of the tumor are important prognostic markers. Epithelial ovarian carcinomas are classified into four major categories: serous, mucinous, endometrioid, and clear cell. Each subtypes of ovarian carcinoma are known to have different clinical characteristics and biological behaviour and response to chemotherapy. Molecular studies have supported for the notion that the different histological types of ovarian cancer likely represent histopathologically, genetically, and biologically distinct diseases. Microarray-based profiling technologies have provided an opportunity to simultaneously examine the relationship between thousands of genes and clinical phenotypes. In this review, we will summarise the current gene-expression profiles that address the classification of ovarian cancer into molecular subtypes with different outcomes.


Assuntos
Neoplasias Ovarianas/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Ovarianas/patologia
19.
Rev. Asoc. Esp. Espec. Med. Trab ; 19(1): 40-47, feb. 2010. graf
Artigo em Espanhol | IBECS | ID: ibc-89194

RESUMO

Objetivos: Afrontar los riesgos del trabajador de la administración pública, como son los trastornos musculoesqueléticos (TME). Para ello se ha desarrollado un programa específico de descarga, atacando dicho riesgo en el propio centro de trabajo, a todos los niveles. Sujetos y métodos: Estudio epidemiológico trasversal sobre 257 trabajadores atendidos en la consulta laboral de este ministerio en el Complejo Cuzco, que acuden a solicitar por su dolencia atención medica e inclusión en el programa, o bien por accidente de trabajo. Resultados: De los 257 pacientes estudiados, el 74% son mujeres y el 26% son hombres. La edad media es de 47 años en hombres y 47,9 en mujeres. La clasificación general de todas las patologíases de un 60% para contracturas y un 40% para tendinitis. La clasificación de los puestos de trabajo estudiados según el código nacional de ocupaciones es del 50,6% para auxiliares administrativos, del 16,8% para jefes de servicio y área, del 12,3% para personal directivo y del 4,49% para trabajadores de informática. El 56,6% presenta patología cervical, el 10,16% lumbar, el 20,94% afectación del miembro superior derecho, el 7,36% columna dorsal y el 5,04% miembro inferior. La evaluación específica de los puestos de trabajo demostró la necesidad de modificaciones en prácticamente el 100% de los casos, para prevenir la cronificación de los TME. El ahorro de horas perdidas evitando el desplazamiento de los trabajadores en el caso máximo fue de casi 2.000. Conclusiones: En los trabajadores de la administración pública, el riesgo más importante es la sobrecarga postural. La implantación de un programa de descarga musculoesquelética permite atacar los riesgos en el origen, ahorrando horas perdidas a la empresa y al trabajador y realizando en consecuencia las modificacionesoportunas en el puesto de trabajo, y evitar la cronificación de las lesiones (AU)


Objective: Minimizing the risk of government employees suffering from work-related ailments like muscle skeletal disorders (MSD). A specific discharge program has been devised to cut down this risk in the very place of work and at all levels. Subject and methods: Transversal epidemiological study on 257 workers treated at this doctor’s office [Cuzco complex of the Treasury Department] due to request of medical attention and inclusion on the program, or due to industrial accident. Results: Demographics of the study are 74% female subjects, 26% male. Average age ± standard deviation is 47,9 years females, 47 years males. General classification of all ailments is contracture for 60% and tendinitis for 40%. Work role classification according to the national occupation code would be a 50,6% of administrative assistants, 16,8% of head of service/ area, 12,3% of management and a 4,49% of I.T. workers. 56,6% of study subjects presented cervical pathology, 10,16% lumbar pathology, 20,94% presented upper right limb symptoms, 7,36% dorsal spine symptoms and a 5,04% presented lower limbs symptoms. Specific evaluation of the working places showed the need for changes in almost the totality of the cases to avoid chronification of the MSD. Time saved with this preventions reached almost 2000 work hours Conclusions: In government administration workers the highest health hazard is postural overcharge. The deployment of a Musculoskeletal Discharge Program allows tackling the hazard in its origins saving hours for company and worker altogether. Appropriate modifications on the workplace avoid injury chronification (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ergonomia/normas , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/prevenção & controle , Postura/fisiologia , Doenças Musculoesqueléticas/prevenção & controle
20.
Dalton Trans ; (37): 7639-47, 2009 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-19759935

RESUMO

The coordination behaviour of the Schiff-base, benzil bis(benzoylhydrazone), LH(2) towards divalent nickel, lead, cadmium, zinc and copper ions has been investigated. The complexes have been fully characterized by techniques including (113)Cd and (207)Pb NMR, as well as (13)C and (113)Cd CP/MAS NMR and by single crystal X-ray diffraction. All the complexes have the general formula [ML](n) (n = 1-3 depending on the metal ion), with the ligand doubly deprotonated. The nickel complex [NiL] is a monomeric compound, the lead complex [PbL](2) shows a binuclear structure, whereas zinc [ZnL](3) and copper [CuL](3) complexes are trinuclear helicates. The cadmium complex seems to be a dimer with a structure similar to that of . In the nickel and lead derivatives, the ligand behaves as a tetradentate N(2)O(2) chelate and in complex also as a bridge through one of the O atoms. In the crystal structures of Zn and Cu complexes [ML](3) each metal is in a pentadentate N(3)O(2) environment formed by two different ligands, one tridentate chelate and the other bidentate chelate, giving rise to trinuclear helicates. These results point out the versatility of benzil bis(benzoylhydrazone) on its coordination.

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