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1.
Pharmaceutics ; 16(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38543218

RESUMO

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM's high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM's aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM's therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.

2.
Neurosci Lett ; 813: 137432, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37549865

RESUMO

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.


Assuntos
Bupropiona , Fluoxetina , Gravidez , Feminino , Camundongos , Animais , Masculino , Fluoxetina/farmacologia , Bupropiona/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Antidepressivos/farmacologia , Natação/psicologia , Hipocampo/metabolismo , Comportamento Animal
3.
Artigo em Inglês | MEDLINE | ID: mdl-37652805

RESUMO

INTRODUCTION AND OBJECTIVE: Flow Cytometry (FC) is one of the techniques, which allows the identification and characterization of platelets. The detection of absent or reduced expression of the glycoproteins is the main objective of this technique. Abnormalities of glycoproteins lead to hemorrhagic syndromes. Among the main diseases, the Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT) stand out. We aimed to show a FC-based platelet assessment test for diagnostic use, which measures the expression of markers in normal patients, and evaluate these markers in patients with platelet disorders. METHODS: We examined a control group of 41 healthy adults to establish reference values and assess the variability of the relative expression of platelet markers and subsequently compared these findings to those of 30 patients with suspected platelet dysfunctions. We determined the mean fluorescent intensity (MFI) of the expressed parameters by FC using CD41, CD42a, CD42b and CD61 and SSC/FSC platelet-gated cells. RESULTS: We determined our baseline panel of markers and compared them to suspected platelet dysfunctions. Patients with suspected BSS presented increased levels of the MFI for the GPIIIa (CD61) and GPIIb (CD41). They showed significantly reduced levels of the GPIb (CD42b) and GPIX (CD42a). Patients with suspected GT showed normal expression of the GPIX (CD42a), increased expression of the GPIb (CD42b) and reduced levels of the GPIIIa (CD61). In this case, with reduced levels of only one marker, the GPIIb (CD41), values showed normal expression. CONCLUSIONS: We describe the FC assay to support the diagnosis of different platelet disorders. Our study made it possible to implement a technique that brought benefits to care.

4.
Pharmaceuticals (Basel) ; 16(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37111343

RESUMO

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 ± 2.87 µM) and K-562R (25.80 ± 3.21 µM) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML.

5.
Arch Pathol Lab Med ; 147(6): 701-709, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36161791

RESUMO

CONTEXT.­: Nucleophosmin 1 (NPM1) mutations affect 20% to 30% of all acute myeloid leukemia (AML) patients; several methods are employed to analyze NPM1 mutations, each of them with its advantages and limitations. OBJECTIVE.­: To compare 3 nonsequencing protocols capable of detecting the main NPM1 mutations and to evaluate nuclear morphometric analysis (NMA) as an alternative to cuplike blast detection. DESIGN.­: We selected multiparameter flow cytometry (MFC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and a quantitative PCR (qPCR) kit to identify NPM1 mutations in AML patients at diagnosis. We also evaluated the presence of cuplike blasts and assessed nuclear morphometry using NMA. RESULTS.­: MFC appears as a screening method for NPM1 mutations because of its lower specificity. ARMS-PCR demonstrated specificity similar to that of the qPCR kit, although it was more laborious. qPCR testing, conversely, is relatively fast and easy to standardize. Of these methods, qPCR was the only one capable of identifying the type of NPM1 mutation. With regard to morphology, NMA could be used as an alternative for the evaluation of cuplike blasts in AML smears. CONCLUSIONS.­: qPCR appears to be the best option to identify NPM1 mutations, with ARMS-PCR representing a cheaper alternative. MFC may be used as a screening method, in which results falling within and above the gray zone should be confirmed by molecular testing.


Assuntos
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Nucleofosmina , Mutação , Núcleo Celular , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética
6.
Cell Biochem Funct ; 39(6): 780-790, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34031899

RESUMO

Stem-like cells (CSCs) have a tumour-initiating capacity and play critical role in tumour metastasis, relapse and resistance to therapy. The ectoenzyme CD73, encoded by the NT5E gene, which catalyses the hydrolysis of AMP into adenosine, has been associated to an immunosuppressive tumour microenvironment, tumour cell adhesion and migration. Therefore, we investigated the expression and activity of CD73 in sphere-forming cells from cervical cancer in comparison to monolayer cells in vitro. In addition, in silico analysis was performed to determine the expression of CD73 and other members of purinergic signalling in CSC-like population derived from different tumour types in comparison to monolayer cells. CD73 protein expression levels and functionality in SiHa cells were analysed by flow cytometry and enzymatic assay, respectively. In silico investigation was performed through the analysis of seven datasets from different tumour types using GEO database. In vitro analysis showed a decreased CD73 protein expression and enzymatic activity in cervical spheres, when compared to monolayers. In addition, when sphere-derived cells are re-plated as monolayer culture, the CD73 expression and activity are restored. Supporting the in vitro results, in silico analysis showed that three-dimensional spheres derived from cervical, thyroid and breast cancer presented decreased expression of CD73, when compared to their adherent counterparts. The decreased expression of CD73 in sphere-derived cells or CSC-enriched population reinforce its important role in cell adhesion, tumour spreading ability and metastasis, suggesting CD73 as potential target to be further investigated in cervical cancer.


Assuntos
5'-Nucleotidase/genética , Microambiente Tumoral/genética , Neoplasias do Colo do Útero/genética , 5'-Nucleotidase/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
7.
ChemMedChem ; 16(12): 1835-1860, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33682360

RESUMO

Chronic myeloid leukemia (CML) is a neoplasm characterized by BCR-ABL1, an oncoprotein with vital role in leukemogenesis. Its inhibition by tyrosine kinase inhibitors represents the main choice of treatment. However, therapeutic failure is worrying given the lack of pharmacological options. Pentacyclic triterpenes are phytochemicals with outstanding antitumoral properties and have also been explored as a basis for the design of potential leads. In this review, we have gathered and discuss data regarding both natural and semisynthetic pentacyclic triterpenes applied to CML cell treatment. We found consistent evidence that the class of pentacyclic triterpenes in general exerts promising pro-apoptotic and antiproliferative activities in sensitive and resistant CML cells, and thus represents a rich source for drug development. We also analyze the predicted drug-like properties of the molecules, discuss the structural changes with biological implications and show the great opportunities this class represents, as well as the perspectives they provide on drug discovery for CML treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Estrutura Molecular , Triterpenos Pentacíclicos/síntese química , Triterpenos Pentacíclicos/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química
8.
Rev. epidemiol. controle infecç ; 10(1): 72-78, jan.-mar. 2020. ilus
Artigo em Português | LILACS | ID: biblio-1179203

RESUMO

Justificativas e Objetivos: Câncer de colo de útero é considerado um problema de saúde pública mundial. Seu diagnóstico é realizado através do exame citopatológico (EC) e seu desenvolvimento relacionado à infecção pelo papilomavírus humano (HPV). Este estudo objetiva avaliar o perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre, Rio Grande do Sul, assim como a relação de alterações observadas ao EC com presença do HPV. Métodos: Estudo transversal realizado em mulheres atendidas em unidades básicas de saúde e um ambulatório de referência de hospital público terciário, no período de julho de 2014 a janeiro de 2017. Coletaram-se amostras representativas da endo/ectocérvice para realização do EC e investigadas quanto à presença molecular do HPV. Resultados: Foram analisadas 169 mulheres com idade média entre 31 e 40 anos, das quais 125 (74%) informaram que a sexarca ocorreu na faixa de 15-20 anos e 37,9% relatou ter tido de três a cinco parceiros sexuais. Em relação ao EC, 71 (42%) apresentaram resultado negativo para lesão intraepitelial ou malignidade e 98 (58%) alguma anormalidade de células escamosas: 20 (11,8%) atipias; 22 (13%) lesão intraepitelial escamosa de baixo grau e 56 (32,6%) lesão intraepitelial de alto grau (HSIL). Cinquenta (29,6%) apresentaram positividade para HPV, destas 56,4% foram diagnosticadas com HSIL (p<0,01). Conclusão: Os resultados revelam alta frequência de HPV em amostras com alterações citopatológicas, em mulheres jovens e com grau de exposição ao HPV, reforçando a importância do papel da sua identificação precoce na investigação da carcinogênese cervical.(AU)


Background and Objectives: Cervical cancer is considered a worldwide public health problem. Its diagnosis is made through cytopathological examination and its development related to human papillomavirus (HPV) infection. This study aims to evaluate the profile of women treated at reference health centers in Porto Alegre, Rio Grande do Sul, as well as the relation of changes observed to cytopathological examination with the presence of HPV. Methods: This is a cross-sectional study carried out in women treated at basic health units and a referral clinic of a public tertiary hospital, from July 2014 to January 2017. Representative samples of the endo/ectocervix were collected to perform the cytopathological examination and investigated for the molecular presence of HPV. Results: 169 women with mean age between 31 and 40 years were analyzed, of whom 125 (74%) reported that the onset of sexual activity occurred in the 15-20 years age group, and 37.9% reported having had three to five sexual partners. In relation to cytopathological examination, 71 (42%) had a negative result for intraepithelial lesion or malignancy and 98 (58%) some squamous cell abnormality: 20 (11.8%) atypical; 22 (13%) low-grade squamous intraepithelial lesion and 56 (32.6%) high-grade intraepithelial lesion (HSIL). Fifty (29.6%) were positive for HPV, of which 56.4% were diagnosed with HSIL (p < 0.01). Conclusion: The results reveal a high frequency of HPV in samples with cytopathological changes, in young women and with a degree of exposure to HPV, reinforcing the importance of the role of its early identification in the investigation of cervical carcinogenesis.(AU)


Justificación y objetivos: El cáncer de cuello uterino se considera un problema de salud pública en todo el mundo. Su diagnóstico se realiza mediante el examen citopatológico (EC), y su desarrollo está relacionado con la infección por el virus del papiloma humano (VPH). Este estudio objetivó evaluar el perfil de mujeres atendidas en los centros de referencia en salud de Porto Alegre, Rio Grande do Sul (Brasil), así como la relación de las alteraciones observadas en el EC con la presencia del VPH. Métodos: Estudio transversal realizado en las mujeres atendidas por unidades de atención primaria y por una clínica ambulatoria de referencia del hospital público terciario en la ciudad de Porto Alegre, en el período de julio de 2014 a enero de 2017. Se recolectaron muestras representativas de endo/ectocérvice para realizar la CE, las cuales se clasificaron según el sistema Bethesda y se investigaron la presencia molecular del VPH. Resultados: Analizamos 169 mujeres con promedio de edad entre 31 y 40 años, de las cuales 125 (74%) informaron que el sexarche ocurrió en el rango de 15-20 años. La mayoría (37,9%) informó haber tenido de 3 a 5 parejas sexuales; y el 37,3% estaban usando anticonceptivos orales. Con respecto a la EC, 71 (42%) se clasificaron como negativos para lesión intraepitelial o malignidad; y el 98 (58%) tenían alguna anormalidad de células escamosas: 20 (11,8%) de atipias; 22 (13,0%) lesión intraepitelial escamosa de bajo grado y 56 (32,6%) lesión intraepitelial de alto grado (HSIL). La frecuencia de positividad del VPH encontrada fue de 50 (29,6%), de estas un 56,4% fueron diagnosticadas con HSIL (p<0,01). Conclusiones: Estos resultados revelan una alta frecuencia de VPH en muestras con alteraciones citopatológicas presentes en mujeres jóvenes con cierto grado de exposición al VPH, lo que refuerza la importancia de identificarse tempranamente en el análisis de la carcinogénesis cervical.(AU)


Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Estudos Transversais , Distribuição por Idade , Teste de Papanicolaou , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia
9.
Purinergic Signal ; 16(1): 29-40, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31955347

RESUMO

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the occurrence of the t(9;22)(q34;q11) translocation. First-line therapy for CML consists of treatment with imatinib mesylate, which selectively inhibits the BCR-ABL protein by competing for its ATP-binding site. Adenine nucleotide signaling is modulated by the ectonucleotidases and this pathway is related to tumorigenic processes. Considering the relationship between ATP and cancer, we aimed to evaluate the influence of imatinib mesylate on the expressions and functions of the NTPDase and ecto-5'-nucleotidase (CD73) enzymes in imatinib-sensitive and -resistant K-562 cell lines. mRNA analysis showed that K-562 cells express all ENTPDs and NT5E. However, when treated with imatinib mesylate for 24 h, the expression of ENTPD1, -2, -3 and -5 increased, leading to a higher nucleotides hydrolysis rate. HPLC analysis identified increased ATP degradation in cells after 24 h of treatment, with consequent ADP and AMP formation, corroborating the increase in gene and protein expression of ectonucleotidases as observed in previous results. On the other hand, we observed that imatinib-resistant K-562 cells presented a decrease in nucleotide hydrolysis and expressions of ENTPD1 and -5. These results suggest an involvement of imatinib in modulating ectonucleotidases in CML that will need further investigation. Since these ectonucleotidases have important catalytic activities in the tumor microenvironment, their modulation in CML cells may represent an important therapeutic approach to regulate levels of extracellular adenine nucleotides.


Assuntos
Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Pirofosfatases/metabolismo , Linhagem Celular Tumoral , Humanos , Pirofosfatases/efeitos dos fármacos
10.
J Glob Infect Dis ; 10(2): 42-46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29910563

RESUMO

INTRODUCTION: Sepsis is a systemic inflammatory response to suspected or confirmed infection. Clinical evaluations are essential for its early detection and treatment. Blood cultures may take as long as 2 days to yield a result and are not always reliable. However, recent studies have suggested that neutrophil CD64 expression may be a sensitive and specific alternative for the diagnosis of systemic infection. OBJECTIVE: The objective of the study was to analyze the difference in CD64 values between subjects with systemic inflammatory response syndrome (SIRS), suspected or confirmed sepsis, who meet diagnostic criteria for SIRS upon arriving at an emergency department. MATERIALS AND METHODS: This was a prospective observational cohort study, an accuracy study of CD64 prospectively evaluated. The sample consisted of 109 patients aged 18 years with criteria for SIRS on arrival to emergency department. CD64 expression was measured within 6 h of hospital admission and once again after 48 h. RESULTS: ROC curve analysis suggested that a cutoff of 1.45 for CD64 expression could diagnose sepsis with a sensitivity of 0.85, a specificity of 0.75, an accuracy of 82.08%, a positive predictive value of 0.96, a negative predictive value of 0.38 and a positive likelihood ratio of 3.33. The area under the curve was 0.83. CONCLUSION: CD64 seems to be a useful, sensitive, and specific biomarker in discriminating between SIRS and sepsis.

11.
J Microbiol Methods ; 141: 121-125, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28822772

RESUMO

Pathogenic Candida species are detected in clinical infections. CHROMagar™ is a phenotypical method used to identify Candida species, although it has limitations, which indicates the need for more sensitive and specific techniques. Infrared Spectroscopy (FT-IR) is an analytical vibrational technique used to identify patterns of metabolic fingerprint of biological matrixes, particularly whole microbial cell systems as Candida sp. in association of classificatory chemometrics algorithms. On the other hand, Soft Independent Modeling by Class Analogy (SIMCA) is one of the typical algorithms still little employed in microbiological classification. This study demonstrates the applicability of the FT-IR-technique by specular reflectance associated with SIMCA to discriminate Candida species isolated from vaginal discharges and grown on CHROMagar™. The differences in spectra of C. albicans, C. glabrata and C. krusei were suitable for use in the discrimination of these species, which was observed by PCA. Then, a SIMCA model was constructed with standard samples of three species and using the spectral region of 1792-1561cm-1. All samples (n=48) were properly classified based on the chromogenic method using CHROMagar™ Candida. In total, 93.4% (n=45) of the samples were correctly and unambiguously classified (Class I). Two samples of C. albicans were classified correctly, though these could have been C. glabrata (Class II). Also, one C. glabrata sample could have been classified as C. krusei (Class II). Concerning these three samples, one triplicate of each was included in Class II and two in Class I. Therefore, FT-IR associated with SIMCA can be used to identify samples of C. albicans, C. glabrata, and C. krusei grown in CHROMagar™ Candida aiming to improve clinical applications of this technique.


Assuntos
Candida/classificação , Candidíase Vulvovaginal/microbiologia , Micologia/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Candida/crescimento & desenvolvimento , Candida/metabolismo , Candida albicans/classificação , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Candida glabrata/classificação , Candida glabrata/crescimento & desenvolvimento , Candida glabrata/metabolismo , Candidíase Vulvovaginal/diagnóstico , Meios de Cultura , Feminino , Humanos , Fenótipo , Descarga Vaginal/microbiologia
12.
Hematol Oncol Stem Cell Ther ; 10(3): 135-142, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28636891

RESUMO

OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. METHODS: Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. RESULTS: Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. CONCLUSION: VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Quimioterapia de Indução/métodos , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estudos Retrospectivos
13.
Int J Hematol Oncol Stem Cell Res ; 11(1): 30-36, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28286612

RESUMO

Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014. Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT. Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.

14.
Cell Reprogram ; 18(6): 369-381, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27906586

RESUMO

Scaffolds produced by electrospinning act as supports for cell proliferation and differentiation, improved through the release of neurotrophic factors. The objective of this study was to develop aligned and random nanofiber scaffolds with and without nerve growth factor to evaluate the potential of mesenchymal stem cells (MSCs) for neural differentiation. Nanofiber morphology, diameter, degradability, cell morphology, adhesion, proliferation, viability, cytotoxicity, and neural differentiation were performed to characterize the scaffolds. The expression for nestin, ß-III tubulin, and neuron-specific enolase was also evaluated. The scaffolds demonstrated a satisfactory environment for MSC growth, being nontoxic. The MSCs cultivated on the scaffolds were able to adhere and proliferate. The evaluation of neural differentiation indicated that in all groups of scaffolds the MSCs were able to upregulate neural gene expression.


Assuntos
Polpa Dentária/citologia , Células-Tronco Mesenquimais/citologia , Neurogênese/fisiologia , Neurônios/citologia , Células-Tronco/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Adipócitos/citologia , Diferenciação Celular , Células Cultivadas , Condrócitos/citologia , Humanos , Nanofibras/química , Osteogênese
15.
Mem Inst Oswaldo Cruz ; 111(2): 106-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26841046

RESUMO

The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis, herpes simplex virus 1 and 2,Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, andTreponema pallidum, besides genotyping for most common high-risk HPV. An association between cytological lesions and different behavioural habits such as smoking and sedentariness was observed. Intraepithelial lesions were also associated with HPV and C. trachomatis detection. An association was also found between both simple and multiple genotype infection and cytological changes. The investigation of HPV and C. trachomatisproved its importance and may be considered in the future for including in screening programs, since these factors are linked to the early diagnosis of patients with precursor lesions of cervical cancer.


Assuntos
Colo do Útero/microbiologia , Chlamydia trachomatis/isolamento & purificação , DNA Viral/isolamento & purificação , Papillomaviridae/isolamento & purificação , Lesões Intraepiteliais Escamosas Cervicais/microbiologia , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Carcinogênese , Colo do Útero/patologia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Coinfecção , Estudos Transversais , Efeito Citopatogênico Viral , Detecção Precoce de Câncer/métodos , Epitélio/virologia , Feminino , Genótipo , Técnicas de Genotipagem , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Tipagem Molecular , Mycoplasma genitalium/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Treponema pallidum/isolamento & purificação , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/microbiologia , Adulto Jovem
16.
Mem. Inst. Oswaldo Cruz ; 111(2): 106-113, Feb. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-772612

RESUMO

The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis, herpes simplex virus 1 and 2,Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, andTreponema pallidum, besides genotyping for most common high-risk HPV. An association between cytological lesions and different behavioural habits such as smoking and sedentariness was observed. Intraepithelial lesions were also associated with HPV and C. trachomatis detection. An association was also found between both simple and multiple genotype infection and cytological changes. The investigation of HPV and C. trachomatisproved its importance and may be considered in the future for including in screening programs, since these factors are linked to the early diagnosis of patients with precursor lesions of cervical cancer.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Colo do Útero/microbiologia , Chlamydia trachomatis/isolamento & purificação , DNA Viral/isolamento & purificação , Papillomaviridae/isolamento & purificação , Lesões Intraepiteliais Escamosas Cervicais/microbiologia , Neoplasias do Colo do Útero/prevenção & controle , Carcinogênese , Coinfecção , Estudos Transversais , Efeito Citopatogênico Viral , Colo do Útero/patologia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Detecção Precoce de Câncer/métodos , Epitélio/virologia , Genótipo , Técnicas de Genotipagem , Herpesvirus Humano 1/isolamento & purificação , /isolamento & purificação , Tipagem Molecular , Mycoplasma genitalium/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Treponema pallidum/isolamento & purificação , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/microbiologia
17.
PLoS One ; 10(7): e0134305, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26222679

RESUMO

Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform. In the present study, we investigated DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26 expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was almost undetectable. We observed higher migratory capacity of HeLa, when compared to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration, indicating that, at least in part, cell migration is regulated by DPPIV/CD26 activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa cells exhibited a significant reduction in adhesion. However this mechanism seems to be mediated independent of DPPIV/CD26. This study demonstrates, for the first time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the effect of sitagliptin phosphate on cell migration and adhesion.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Movimento Celular/fisiologia , Dipeptidil Peptidase 4/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Feminino , Células HeLa , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Fosfato de Sitagliptina/farmacologia
18.
Rev. bras. anal. clin ; 47(1-2): 34-38, 2015. graf, tab
Artigo em Português | LILACS | ID: biblio-835828

RESUMO

Objetivo: Caracterizar os candidatos quanto ao gênero e analisar a prevalência dos critérios de inaptidão adotados às doações de sangue, realizadas no Banco de Sangue Santa Maria, em Santa Maria, RS. Métodos: Dados retrospectivos arquivados foram avaliados, analisando-se os critérios de exclusão na triagem clínica e sorológica, no período de janeiro de 2005 até dezembro de 2010. Foram analisados 20.264 doadores. O estudo foi aprovado pelo Comitê de Ética e Pesquisa da Universidade Federal do Rio Grande do Sul-UFRGS, sob número de protocolo 18147. Resultados: Novecentos e setenta e seis (5%) candidatos foram considerados inaptos pela triagem clínica e 19.288 (95%) foram considerados aptos para prosseguirem com os testes laboratoriais. Dos doadores aptos, 941 (5%) foram excluídos na triagem sorológica, totalizando 18.347 bolsas de sangue disponíveis para uso. Predominaram os doadores do sexo masculino (62%) e a principal causa de exclusão, na triagem clínica, foi hipertensão (0,7%). Para a triagem sorológica, a principal causa de exclusão foi a Doença de Chagas (1,5%). Conclusão: Ressaltou-se a importância da triagem clínica, tendo em vista que ela excluiu 5% dos candidatos à doação e a relevância da triagem sorológica ser feita corretamente, evitando que resultados falso-negativos sejam liberados.


Objective: Characterize donors by gender and analyze theprevalence of the inability criteria of donations made at the SantaMaria Blood Bank, located at Santa Maria, Brazil. Methods: First,we searched historical data for exclusion criteria used in clinicaland serological screenings during the period from January, 2005 toJuly, 2010. We evaluated 20,264 blood donors' data for this study.The Ethical Committee of Rio Grande do Sul Federal UniversityUFRGSapproved this study under the protocol number 18147.Results: Nine hundred and seventy-six (5%) candidates wereconsidered unfit by the clinical screening and 19,288 (95%) wereconsidered fit. From the resulting fit population of the clinicalscreening, 941 (5%) were excluded from donating by the serologicalscreening, totaling 18.347 blood donations fit for use. The resultsshows that majority of the donors were male (62%) and the leadingcause of exclusion from donating in the clinical screening washypertension (0.7%). As for the serological screening, the leadingcause for exclusion was Chagas disease (1.5%). Conclusion: Thestudy stress the importance of the clinical screening process, giventhat it excluded 5% of blood donations, which were unfit for use. Wealso notice the relevance of a correctly done serological screening,thus avoiding that false-negative results are released.


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Bancos de Sangue , Doadores de Sangue , Seleção do Doador
19.
Rev Inst Med Trop Sao Paulo ; 56(2): 93-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24626408

RESUMO

A novel SYBR® green-real time polymerase chain reaction (qPCR) was developed to detect two Bartonella species, B. henselae and B. clarridgeiae, directly from blood samples. The test was used in blood samples obtained from cats living in animal shelters in Southern Brazil. Results were compared with those obtained by conventional PCR targeting Bartonella spp. Among the 47 samples analyzed, eight were positive using the conventional PCR and 12 were positive using qPCR. Importantly, the new qPCR detected the presence of both B. henselae and B. clarridgeiae in two samples. The results show that the qPCR described here may be a reliable tool for the screening and differentiation of two important Bartonella species.


Assuntos
Infecções por Bartonella/veterinária , Bartonella/genética , Bartonella/isolamento & purificação , Doenças do Gato/microbiologia , DNA Bacteriano/sangue , Reação em Cadeia da Polimerase Multiplex/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Infecções por Bartonella/microbiologia , Bartonella henselae/genética , Bartonella henselae/isolamento & purificação , Gatos , Especificidade da Espécie
20.
Pediatr Pulmonol ; 48(11): 1112-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23818319

RESUMO

BACKGROUND: Acute viral bronchiolitis (AVB) remains the leading cause of lower respiratory tract infection (LRTI) in infants under 2 years of age. Advances in molecular methods for virus detection have led to the identification of new infectious agents implicated in the development of AVB, such as human bocavirus (HBoV). OBJECTIVES: To ascertain the frequency, seasonality, and clinical behavior of HBoV detection in a series of episodes of LRTI. STUDY DESIGN: The frequency of HBoV was assessed in children with LRTI episodes, aged 1-24 months, seen at the emergency department of Hospital da Criança Santo Antônio, Porto Alegre, Brazil, between May 2007 and July 2008. Virus-specific polymerase chain reaction was used for detection. RESULTS: A total of 455 nasal secretion samples were collected from 433 patients over a 14-month period. Of these, 60 were positive for HBoV (13.2%). Mean age was 7.9 months and 55% of patients were male. Just over half of patients were under 6 months of age (53.3%). Wheezing was the presenting respiratory complaint in 51.7%. Of the 60 patients, 80% were admitted to a pediatric ward. Diarrhea was present in nine patients (18%). Co-detection was a frequent finding in our sample, occurring in 95% of cases. In our series, the distribution of HBoV was clearly seasonal and was influenced by temperature, relative humidity, and precipitation. CONCLUSIONS: We conclude that HBoV detection in infants with AVB and recurrent wheezing of viral etiology in Brazil is similar to that reported in other countries. The clinical course of HBoV detection is no different from that of other respiratory viruses commonly found in this age range.


Assuntos
Bocavirus Humano , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Masculino
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