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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731966

RESUMO

Leukemias are among the most prevalent types of cancer worldwide. Bone marrow mesenchymal stem cells (MSCs) participate in the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases such as leukemias, to a yet unknown extent. Here we described the effect of secretome of bone marrow MSCs obtained from healthy donors and from patients with acute myeloid leukemia (AML) on leukemic cell lineages, sensitive (K562) or resistant (K562-Lucena) to chemotherapy drugs. Cell proliferation, viability and death were evaluated, together with cell cycle, cytokine production and gene expression of ABC transporters and cyclins. The secretome of healthy MSCs decreased proliferation and viability of both K562 and K562-Lucena cells; moreover, an increase in apoptosis and necrosis rates was observed, together with the activation of caspase 3/7, cell cycle arrest in G0/G1 phase and changes in expression of several ABC proteins and cyclins D1 and D2. These effects were not observed using the secretome of MSCs derived from AML patients. In conclusion, the secretome of healthy MSCs have the capacity to inhibit the development of leukemia cells, at least in the studied conditions. However, MSCs from AML patients seem to have lost this capacity, and could therefore contribute to the development of leukemia.


Assuntos
Proliferação de Células , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/genética , Células K562 , Apoptose , Secretoma/metabolismo , Pessoa de Meia-Idade , Feminino , Masculino , Células da Medula Óssea/metabolismo , Linhagem da Célula/genética , Sobrevivência Celular , Adulto
2.
Cancers (Basel) ; 16(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38672542

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials. METHODS: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols. RESULTS: The median age at diagnosis was 75 years (70-97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate-high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR (p = 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia (p = 0.001), IPI ≥ 3 (p = 0.013), and NCCN-IPI ≥ 3 (p = 0.002). Although associated with higher rates of severe neutropenia (p = 0.003), the R-CHOP regimen promoted increased OS (p = 0.003) and PFS (p = 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort. CONCLUSIONS: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38656040

RESUMO

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.


Assuntos
Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , SARS-CoV-2 , Humanos , Hospedeiro Imunocomprometido/imunologia , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Idoso , Imunocompetência/imunologia , Adulto Jovem , Imunização Secundária
4.
EJHaem ; 5(1): 147-152, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406522

RESUMO

After initiating combined antiretroviral therapy (cART), individuals with human immunodeficiency virus (HIV) may develop Hodgkin/non-Hodgkin lymphoma due to immune reconstitution inflammatory syndrome (IRIS). This retrospective cohort study evaluated the incidence, clinical features and prognosis of IRIS-associated lymphomas in Brazilian patients. Incidence in 2000-2019 was 9.8% (27/276 patients with HIV and lymphoma; viral load drop >1 log). Time between HIV diagnosis and cART initiation was <1 year in 70.3% of cases. Time between cART initiation and lymphoma diagnosis was <3 months in 11 cases and 3-6 months in 16 cases. Overall and progression-free survival rates were similar between cases of non-IRIS-associated lymphoma and IRIS-associated lymphoma.

6.
Spec Care Dentist ; 44(2): 300-313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37287115

RESUMO

AIMS: Immune-related adverse events (irAEs) linked to the use of immune checkpoint inhibitors (ICIs) have become increasingly frequent. To perform a bibliometric and critical review of the general panorama of publications on oral mucosal lesions (OML) associated with ICIs. METHODS AND RESULTS: Systematized searches were performed in four databases. The included studies were organized and bibliometric and clinical data were extracted and analyzed using VantagePoint and Microsoft Excel. Most of the 35 included studies were reports or case series (n = 33/94.2%). The American authors stood out (n = 17/48.5%), with the majority presenting only one publication. Independent groups carried out most of the publications (n = 31/88.5%). Over the years, publications have increased for users of nivolumab and pembrolizumab. In 21 studies (60%), OML were more common in men, between the 6th and 9th decades of life and who had lung carcinoma (n = 13/37.1%). Pembrolizumab (n = 17/48.5%) was the most used ICI. The patients were affected by one or more OML, including: ulcers (n = 28/80%) and erythema (n = 11/31.4%). Systemic corticosteroids (n = 24/68.5%) and the discontinuation of ICI use (n = 18/51.4%) were the main approaches used. CONCLUSION: OML related to the use of ICIs have become increasingly common. More accurate data need to be published.


Assuntos
Antineoplásicos Imunológicos , Masculino , Humanos , Estados Unidos , Antineoplásicos Imunológicos/efeitos adversos , Mucosa Bucal , Nivolumabe/efeitos adversos , Bibliometria
9.
Cancers (Basel) ; 15(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37835453

RESUMO

BACKGROUND: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. METHODS: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. RESULTS: The median age at diagnosis was 65 years (38-89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. CONCLUSIONS: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.

10.
Free Radic Biol Med ; 209(Pt 1): 29-39, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37774804

RESUMO

Aging is a time-related functional decline that affects many species. One of the hallmarks of aging is mitochondrial dysfunction, which leads to metabolic decline. The NAD decline during aging, in several tissues, correlates with increase in NADase activity of CD38. Knock out or pharmacological inhibition of CD38 activity can rescue mitochondrial function in several tissues, however, the role of CD38 in controlling NAD levels and metabolic function in the aging brain is unknown. In this work, we investigated CD38 NADase activity controlling NAD levels and mitochondrial function in mice brain with aging. We demonstrate that NADase activity of CD38 does not dictate NAD total levels in brain of aging mice and does not control mitochondrial oxygen consumption nor other oxygen parameters markers of mitochondrial dysfunction. However, for the first time we show that CD38 regulates hydrogen peroxide (H2O2) generation, one of the reactive oxygen species (ROS) in aging brain, through regulation of pyruvate dehydrogenase and alfa-ketoglutarate dehydrogenase, as mitochondria H2O2 leakage sites. The effect may be related to mitochondrial calcium handling differences in CD38 absence. Our study highlights a novel role of CD38 in brain energy metabolism and aging.


Assuntos
Peróxido de Hidrogênio , NAD+ Nucleosidase , Camundongos , Animais , NAD+ Nucleosidase/metabolismo , ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/metabolismo , Peróxido de Hidrogênio/metabolismo , NAD/metabolismo , Encéfalo/metabolismo , Mitocôndrias/metabolismo , Oxirredutases/metabolismo
11.
Front Oncol ; 13: 1175545, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529691

RESUMO

Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive malignancy with significant racial and geographic variations worldwide. In addition to the formerly "nasal-type" initial description, these lymphomas are predominantly extranodal in origin and typically cause vascular damage and tissue destruction, and although not fully understood, Epstein-Barr virus (EBV) has an important role in its pathogenesis. Initial assessment must include a hematopathology review of representative and viable tumor areas without necrosis for adequate immunohistochemistry studies, including EBV-encoded small RNA (EBER) in situ hybridization (ISH). Positron emission tomography with 18-fluorodeoxyglucose (18F-FDG-PET/CT) for accurate staging is essential, and most patients will have localized disease (IE/IIE) at diagnosis. Apart from other T-cell malignancies, the best treatment even for localized cases is combined modality therapy (chemotherapy plus radiotherapy) with non-anthracycline-based regimens. For advanced-stage disease, l-asparaginase-containing regimens have shown improved survival, but relapsed and refractory cases have very poor outcomes. Nowadays, even with a better understanding of pathogenic pathways, up-front therapy is completely based on chemotherapy and radiotherapy, and treatment-related mortality is not low. Future strategies targeting signaling pathways and immunotherapy are evolving, but we need to better identify those patients with dismal outcomes in a pre-emptive way. Given the rarity of the disease, international collaborations are urgently needed, and clinical trials are the way to change the future.

12.
Blood Adv ; 7(20): 6339-6350, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37530631

RESUMO

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma não Hodgkin , Linfoma de Células T , Linfoma , Trombocitopenia , Humanos , Adolescente , Adulto , Valganciclovir/uso terapêutico , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Recidiva Local de Neoplasia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma/tratamento farmacológico , Trombocitopenia/patologia
13.
Virulence ; 14(1): 2230015, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37394816

RESUMO

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , MicroRNAs , Paraparesia Espástica Tropical , Humanos , Prognóstico , Paraparesia Espástica Tropical/genética , Paraparesia Espástica Tropical/complicações , Paraparesia Espástica Tropical/patologia , Vírus Linfotrópico T Tipo 1 Humano/genética , MicroRNAs/genética , Biomarcadores
14.
Int J Mol Sci ; 24(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37445821

RESUMO

Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Vírus Linfotrópico T Tipo 1 Humano/genética , RNA , Linfoma/complicações
15.
Hematol., Transfus. Cell Ther. (Impr.) ; 45(supl.2): S153-S156, July 2023. graf
Artigo em Inglês | LILACS | ID: biblio-1514207

RESUMO

According to the World Health Organization, trauma from external causes remains the major cause of death and disability among people aged from 5 to 29 years old.1 In order to reestablish hemodynamic stability and adequate hemostasis of these patients, without the dilutional effects of infusing large volumes of crystalloids, the concept of hemostatic resuscitation was developed.2 The purpose of this report is to discuss a case in which hemostatic resuscitation was performed quickly, resulting in a good macro-hemodynamic response of the patient at the first prehospital transfusion service in Latin America.


Assuntos
Humanos , Feminino , Adulto , Transfusão de Sangue , Serviços Médicos de Emergência , Relatos de Casos , Hemodinâmica
16.
Front Oncol ; 13: 1177590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182145

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is the second most frequent subtype of mature T-cell lymphoma (MTCL) in the Western world. It derives from the monoclonal proliferation of T-follicular helper (TFH) cells and is characterized by an exacerbated inflammatory response and immune dysregulation, with predisposition to autoimmunity phenomena and recurrent infections. Its genesis is based on a multistep integrative model, where age-related and initiator mutations involve epigenetic regulatory genes, such as TET-2 and DNMT3A. Subsequently, driver-mutations, such as RhoA G17V and IDH-2 R172K/S promote the expansion of clonal TFH-cells ("second-hit"), that finally begin to secrete cytokines and chemokines, such as IL-6, IL-21, CXCL-13 and VEGF, modulating a network of complex relationships between TFH-cells and a defective tumor microenvironment (TME), characterized by expansion of follicular dendritic cells (FDC), vessels and EBV-positive immunoblasts. This unique pathogenesis leads to peculiar clinical manifestations, generating the so-called "immunodysplastic syndrome", typical of AITL. Its differential diagnosis is broad, involving viral infections, collagenosis and adverse drug reactions, which led many authors to use the term "many-faced lymphoma" when referring to AITL. Although great advances in its biological knowledge have been obtained in the last two decades, its treatment is still an unmet medical need, with highly reserved clinical outcomes. Outside the setting of clinical trials, AITL patients are still treated with multidrug therapy based on anthracyclines (CHOP-like), followed by up-front consolidation with autologous stem cell transplantation (ASCT). In this setting, the estimated 5-year overall survival (OS) is around 30-40%. New drugs, such as hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDAi), have been used for relapsed/refractory (R/R) disease with promising results. Such agents have their use based on a biological rationale, have significant potential to improve the outcomes of patients with AITL and may represent a paradigm shift in the therapeutic approach to this lymphoma in the near future.

17.
Vet Parasitol ; 318: 109929, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37080069

RESUMO

Citrus fruits are consumed all over the world and their by-products are used for animal feed and essential oils production. This study aimed to evaluate the in vitro and in vivo activity of Citrus aurantium var. Dulcis essential oil (CaEO) combined with ABZ against benzimidazole resistant Haemonchus contortus. In vitro egg hatching assays (EHA) were performed using CaEO and ABZ to estimate the effective concentration to achieve 50% egg death (EC50) values and calculate the test essential oil and drug combinations using a simplex-centroid mixture design. These concentrations were used for a second round of EHAs. Sixteen sheep were randomly allocated into two groups and treated with ABZ and the combination of CaEO and ABZ, and faecal egg count reduction tests were performed. In the first round of EHA, CaEO and ABZ showed EC50 values of 0.57 and 0.0048 mg mL-1, respectively. The H. contortus strain used in the study was shown to be highly benzimidazole resistant, with only 1.5% of parasites having susceptible ß-tubulin SNP genotypes. The ABZ reduced the shedding of nematode eggs by 78%, however, its combination with CaEO reduced faecal egg counts by only 9%. The present study is important to highlight the interferences of natural products in anthelmintic metabolism and consequently in drug efficacy.


Assuntos
Anti-Helmínticos , Citrus , Hemoncose , Haemonchus , Nematoides , Óleos Voláteis , Doenças dos Ovinos , Animais , Ovinos , Albendazol/farmacologia , Albendazol/uso terapêutico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Benzimidazóis/farmacologia , Fezes/parasitologia , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia , Contagem de Ovos de Parasitas/veterinária , Resistência a Medicamentos , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Hemoncose/parasitologia
18.
AIDS ; 37(8): 1217-1226, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939075

RESUMO

OBJECTIVE: To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil. DESIGN: A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil. METHODS: The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4 + lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome. RESULTS: Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n  = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4 + cell count of <200 cells/µl was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score. CONCLUSIONS: HIV status, CD4 + -lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas.


Assuntos
Infecções por HIV , Linfoma Relacionado a AIDS , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Masculino , Adulto , Adolescente , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Estudos Retrospectivos , Brasil/epidemiologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/complicações , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
19.
Healthcare (Basel) ; 11(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36900728

RESUMO

Colorectal cancer (CRC) burden across the world is expected to increase by ~2.2 million new cases and ~1.1 million deaths by 2030. Regular physical exercise is recommended to prevent CRC, but the myriad of protocols preclude further discussion on how to manage its variables for this population. Home-based exercise guided by remote monitoring provides an alternative to surpass the barriers of supervised exercise. However, no meta-analysis was conducted to verify the effectiveness of this intervention for improving physical activity (PA). We performed a systematic review of remote and unsupervised strategies imposed on CRC patients for improving PA and compared, via a meta-analysis, their effectiveness against CRC patients submitted to usual care or no intervention. The databases PubMed, Scopus, and Web of Science were searched on 20 September 2022. Eleven studies attained the criteria for eligibility in the qualitative approach, and seven were included in the meta-analysis. No significant effect (p = 0.06) of remote and unsupervised exercise intervention was observed. However, a sensitivity analysis including three studies that only considered CRC patients was performed, demonstrating a significant effect in favor of exercise (p = 0.008). Based on our sensitivity analysis, remote and unsupervised exercise strategies were effective to improve the PA of CRC patients.

20.
Saude e pesqui. (Impr.) ; 16(1): e-11402, jan.-mar. 2023.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1438131

RESUMO

O presente estudo teve como objetivo estudar a associação entre a exposição ao glifosato e a ocorrência do Transtorno do Espectro Autista (TEA). Trata-se de um estudo documental com busca de dados acerca da prevalência do TEA (Centers of Disease Control and Prevention) e de um levantamento para verificar o princípio ativo do praguicida mais usado no Brasil (Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis) e no mundo (United States Evironmental Prevention Agency). Os resultados mostraram que a prevalência do TEA aumentou ao longo dos anos. Do mesmo modo, o uso e a compra de praguicidas também aumentaram, sendo o glifosato o princípio ativo mais usado. Ainda que os resultados apontem a existência de uma relação entre a exposição ao glifosato e a ocorrência de autismo, são necessários mais estudos para afirmar o potencial neurotóxico do glifosato e sua associação com o nascimento de crianças autistas.


The present study aimed to study the association between exposure to glyphosate and the occurrence of Autistic Spectrum Disorder (ASD). This is a documental study with search for data about the prevalence of ASD (Centers of Disease Control and Prevention) and a survey to verify the active principle of the most used pesticide in Brazil (Brazilian Institute of Environment and Renewable Natural Resources) and worldwide (United States Environmental Prevention Agency). The results showed that the prevalence of ASD increased over the years. Likewise, the use and purchase of pesticides have also increased, with glyphosate being the most widely used active ingredient in the world. Although the results point to the existence of a relationship between exposure to glyphosate and the occurrence of autism, further studies are needed to confirm the neurotoxic potential of glyphosate and its association with the birth of autistic children.

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