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1.
Microb Pathog ; 193: 106769, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955237

RESUMO

The bacterium Escherichia coli is one of the main causes of urinary tract infections. The formation of bacterial biofilms, especially associated with the use of urinary catheters, contributes to the establishment of recurrent infections and the development of resistance to treatment. Strains of E. coli that produce extended-spectrum beta-lactamases (ESBL) have a greater ability to form biofilms. In addition, there is a lack of drugs available in the market with antibiofilm activity. Promethazine (PMZ) is an antihistamine known to have antimicrobial activity against different pathogens, including in the form of biofilms, but there are still few studies of its activity against ESBL E. coli biofilms. The aim of this study was to evaluate the antimicrobial activity of PMZ against ESBL E. coli biofilms, as well as to assess the application of this drug as a biofilm prevention agent in urinary catheters. To this end, the minimum inhibitory concentration and minimum bactericidal concentration of PMZ in ESBL E. coli strains were determined using the broth microdilution assay and tolerance level measurement. The activity of PMZ against the cell viability of the in vitro biofilm formation of ESBL E. coli was analyzed by the MTT colorimetric assay and its ability to prevent biofilm formation when impregnated in a urinary catheter was investigated by counting colony-forming units (CFU) and confirmed by scanning electron microscopy (SEM). PMZ showed bactericidal activity and significantly reduced (p < 0.05) the viability of the biofilm being formed by ESBL E. coli at concentrations of 256 and 512 µg/ml, as well as preventing the formation of biofilm on urinary catheters at concentrations starting at 512 µg/ml by reducing the number of CFUs, as also observed by SEM. Thus, PMZ is a promising candidate to prevent the formation of ESBL E. coli biofilms on abiotic surfaces.

2.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979984

RESUMO

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.


Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Propafenona , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Propafenona/farmacologia , Humanos , Itraconazol/farmacologia , Sinergismo Farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Reposicionamento de Medicamentos
3.
Heliyon ; 10(12): e32624, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975149

RESUMO

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.

4.
Clinics (Sao Paulo) ; 79: 100422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972247

RESUMO

OBJECTIVE: Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. METHODS: This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. RESULTS: EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. CONCLUSION: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.


Assuntos
Adenocarcinoma , Proteínas do Citoesqueleto , Perfilação da Expressão Gênica , Neoplasias Gástricas , Neoplasias do Colo do Útero , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Proteínas do Citoesqueleto/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Feminino , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , RNA Mensageiro , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética
5.
J Dent ; 148: 105216, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950768

RESUMO

OBJECTIVE: To digitally evaluate the three-dimensional (3D) remodelling of FGG used to treat RT2 gingival recessions and lack of keratinized tissue on mandibular incisor teeth. METHODS: Data from 45 patients included in a previous multicentric RCT were analyzed. Silicone impressions were taken before (baseline) and 3, 6 and 12 months after standardized FGG placement. Casts were scanned and images were superimposed, using digital software, to obtain measurements of estimated soft tissue thickness (eTT; 1, 3, and 5 mm apical to baseline gingival margin). In addition, soft tissue volume (STV) and creeping attachment (CA) were assessed. RESULTS: All patients exhibited postoperative eTT and STV increases, at all time points. The greatest mean thickness gain was observed at eTT3 (1.0 ± 0.4 mm) at 12 months. At 12 months, STV was 52.3 ± 21.1 mm3, without relevant changes compared to the 3- and 6-month follow-up. CA, which was observed as early as six months postoperatively, was evident in ∼85 % of teeth at 12 months. CONCLUSIONS: Application of FGG was an effective phenotype modification therapy, as shown by the significantly increased tissue thickness postoperatively. Despite the use of FGG technique not aiming for root coverage, digital 3D assessment documented the early and frequent postoperative occurrence of CA, which helped improve recession treatment outcomes. CLINICAL SIGNIFICANCE: The use of 3D assessment methodology allows precise identification of the tissue gain obtained with FGG, which, regardless of technique, results in predictable phenotype modification and frequent occurrence of creeping attachment.

6.
Arq Bras Cardiol ; 121(6): e20230588, 2024 Jun.
Artigo em Português, Inglês | MEDLINE | ID: mdl-39016410

RESUMO

BACKGROUND: It is unknown whether lymphopenia is a risk factor for the reactivation of Chagas disease in heart transplantation (HTx), as recently described in the reactivation of cytomegalovirus in transplant patients. OBJECTIVE: To evaluate whether lymphopenia in the perioperative period of heart transplantation is related to early Trypanosoma cruzi parasitemia. METHODS: This observational, retrospective study analyzed a sample from January 2014 to January 2023). Parasitemia was evaluated in the first 3 months after HTx using serum polymerase chain reaction (PCR) and compared with the total lymphocyte count in the perioperative period of HTx using receiver operating characteristic curves. Baseline characteristics were compared with PCR for Chagas using independent Cox proportional hazards models. A significance level of 5% was adopted. RESULTS: The sample (n = 35) had a mean age of 52.5 ± 8.1 years, and 22 patients (62.8%) had positive PCR for Chagas. The mean lowest lymphocyte values in the first 14 days after HTx were 398 ± 189 and 755 ± 303 cells/mm3 in patients with and without parasitemia, respectively, within 3 months after HTx (area under the curve = 0.857; 95% confidence interval: 0.996 to 0.718, sensitivity and specificity of 83.3% and 86.4%). A cutoff value of less than 550 lymphocytes/mm3 was determined as a risk factor for the presence of parasitemia. Patients with lymphocytes < 550 units/mm3 in the first 14 days after HTx presented positive PCR in 80% of cases. For every increase of 100 lymphocytes/mm3, the risk of PCR positivity was reduced by 26% (hazard rate ratio = 0.74; 95% confidence interval: 0.59 to 0.93, p = 0.009). CONCLUSION: There was an association between lymphopenia in the perioperative period of HTx and early T. cruzi parasitemia detected by PCR.


FUNDAMENTO: É desconhecido se a linfopenia é fator de risco para a reativação da doença de Chagas no transplante cardíaco (TxC), como recentemente descrito na reativação de citomegalovírus em pacientes transplantados. OBJETIVO: Avaliar se a linfopenia no perioperatório do TxC está relacionada à parasitemia precoce pelo Trypanosoma cruzi. MÉTODOS: Amostra analisada (janeiro de 2014 a janeiro de 2023) em estudo observacional e retrospectivo. A parasitemia foi avaliada nos primeiros 3 meses após o TxC por meio da reação em cadeia da polimerase sérica (PCR) e comparada com a contagem total de linfócitos no perioperatório do TxC por curvas ROC. Comparadas características de base com a PCR Chagas por modelos de risco proporcionais de Cox independentes. Nível de significância adotado de 5%. RESULTADOS: Amostra (n = 35) apresentou idade média de 52,5 ± 8,1 anos e PCR Chagas positiva em 22 pacientes (62,8%). As médias dos menores valores de linfócitos nos primeiros 14 dias do TxC foram 398 ± 189 e 755 ± 303 células/mm3 em pacientes com e sem parasitemia nos 3 meses após o TxC, respectivamente (área sob a curva = 0,857; intervalo de confiança de 95%: 0,996 a 0,718, sensibilidade e especificidade de 83,3% e 86,4%). Determinado valor de corte inferior a 550 linfócitos/mm3 como fator de risco para presença de parasitemia. Pacientes com linfócitos < 550 unidades/mm3 nos primeiros 14 dias do pós-TxC apresentaram PCR positiva em 80% dos casos. Para cada aumento de 100 linfócitos/mm3, o risco de positividade da PCR é reduzido em 26% (razão de riscos = 0,74; intervalo de confiança de 95%: 0,59 a 0,93, p = 0,009). CONCLUSÃO: Houve associação entre a linfopenia no perioperatório do TxC com a parasitemia precoce pelo T. cruzi detectada por PCR.


Assuntos
Doença de Chagas , Transplante de Coração , Linfopenia , Parasitemia , Reação em Cadeia da Polimerase , Trypanosoma cruzi , Humanos , Transplante de Coração/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Estudos Retrospectivos , Contagem de Linfócitos , Doença de Chagas/complicações , Reação em Cadeia da Polimerase/métodos , Adulto , Fatores de Risco , Fatores de Tempo , Valor Preditivo dos Testes , Cardiomiopatia Chagásica/cirurgia , Cardiomiopatia Chagásica/sangue , Curva ROC
7.
Future Microbiol ; : 1-14, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012219

RESUMO

Aim: To evaluate the antifungal activity of mangiferin against Candida spp. resistant to fluconazole. Materials & methods: The antifungal activity of mangiferin was assessed using broth microdilution and its interaction with azoles and amphotericin B was evaluated by checkerboard. The activity of mangiferin against Candida spp. biofilms was assessed using the MTT colorimetric assay and its possible mechanism of action was evaluated using flow cytometry. Results: Mangiferin showed activity against Candida albicans, Candida tropicalis and Candida parapsilosis resistant to fluconazole and showed synergism with azoles and amphotericin B. Mangiferin increased the activity of antifungals against Candida biofilms and caused depolarization of the mitochondrial membrane and externalization of phosphatidylserine, suggesting apoptosis. Conclusion: mangiferin combined with antifungals has potential against Candida spp.


Candida is a type of fungus that can make people ill. Over time, many species of Candida have found ways to resist the drugs used to kill them. It is important to find new drugs. We decided to see if a substance called mangiferin works against Candida. We found that mangiferin works against Candida and may help other drugs to work better. We still need to do more studies to find out whether mangiferin can help prevent diseases caused by Candida in the future.

8.
J Surg Oncol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845222

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management. METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards. CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

9.
Pediatr Transplant ; 28(5): e14814, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38895799

RESUMO

There are no standard management protocols for the treatment of bile leak (BL) after liver transplantation. The objective of this study is to describe treatment options for BL after pediatric LT. METHODS: Retrospective analysis (January 2010-March 2023). VARIABLES STUDIED: preoperative data, status at diagnosis, and postoperative outcome. Four groups: observation (n = 9), percutaneous transhepatic cholangiography (PTC, n = 38), ERCP (2), and surgery (n = 27). RESULTS: Nine hundred and thirty-one pediatric liver transplantation (859 LDLT and 72 DDT); 78 (8.3%) patients had BL, all in LDLT. The median (IQR) peritoneal bilirubin (PB) level and fluid-to-serum bilirubin ratio (FSBR) at diagnosis was 14.40 mg/dL (8.5-29), and 10.7 (4.1-23.7). Patients who required surgery for treatment underwent the procedure earlier, at a median of 14 days (IQR: 7-19) versus 22 days for PTC (IQR: 15-27, p = 0.002). PB and FSBR were significantly lower in the observation group. In 11 cases, conservative management had resolution of the BL in an average time of 35 days, and 38 patients underwent PTC in a median time of 22 days (15-27). Twenty-seven (34.6%) patients were reoperated as initial treatment for BL in a median time of 17 days (1-108 days); 25 (33%) patients evolved with biliary stricture, 5 (18.5%) after surgery, and 20 (52.6%) after PTC (p = 0.01). CONCLUSION: Patients with BL who were observed presented significantly lower levels of PB and FSBR versus those who underwent PTC or surgery. Patients treated with PTC presented higher rates of biliary stricture during the follow-up.


Assuntos
Transplante de Fígado , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia , Colangiopancreatografia Retrógrada Endoscópica , Colangiografia , Adolescente , Bile , Resultado do Tratamento
10.
Beilstein J Org Chem ; 20: 1167-1178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887581

RESUMO

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

11.
Polymers (Basel) ; 16(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891423

RESUMO

Galactomannans are polysaccharides obtained from legume seed extraction. They present a chemical structure consisting of D-mannose chains linked by glycosidic bonds and galactose branches. The main focus lies in their use as thickeners in the food industry, aimed at improving the dielectric properties of food during heating processes within the radiofrequency and microwave ranges. In this work, the prepared galactomannan samples were electrically analyzed through impedance spectroscopy, which is a powerful physical technique. From the experimental measurements, the dielectric permittivity and loss tangent of the galactomannan solutions were analyzed and the electrical modulus formalism was used to study the dielectric relaxations. Crude galactomannans exhibited higher values of permittivity, conductivity, and losses compared to purified galactomannans. Increasing ethanol concentration in galactomannan purification causes an increase in the permittivity and conductivity of galactomannan solutions. In a 1% solution, at 1 kHz, the permittivity increased from 378.56 to 538.09, while in the 2% solution, this increase was from 656.22 to 1103.24. Regarding the conductivity, at the same frequency, the increase was from 1.6 × 10-3 to 3.3 × 10-3 Ω-1m-1 and from 2.9 × 10-3 to 5.5 × 10-3 Ω-1m-1, respectively. The rise of the ethanol concentration in galactomannan purification led to a decrease in the relaxation time, from 448.56 to 159.15 µs and from 224.81 to 89.50 µs in the solution with 1 and 2%, respectively. The results suggest that galactomannan from Adenanthera pavonina L. has potential for use in the food industry.

12.
Sports (Basel) ; 12(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38921858

RESUMO

A variable pacing profile is common in different endurance events. In these races, several factors, such as changes in elevation or race dynamics, lead participants to perform numerous surges in intensity. These surges are so frequent that certain events, such as cross-country (XC) skiing, mountain biking (MTB), triathlon, and road cycling, have been termed "intermittent endurance events". The characteristics of these surges vary depending on the sport: MTB and triathlon require athletes to perform numerous short (<10 s) bouts; XC skiing require periods of short- and moderate-(30 s to 2 min) duration efforts, while road cycling is comprised of a mix of short-, moderate-, and long-duration (>2 min) bouts. These bouts occur at intensities above the maximal metabolic steady state (MMSS), with many efforts performed at intensities above the athletes' maximal aerobic power or speed (MAP/MAS) (i.e., supramaximal intensities). Given the factors that influence the requirement to perform surges in these events, athletes must be prepared to always engage in a race with a highly stochastic pace. The aim of this review is to characterize the variable pacing profile seen in endurance events and to discuss how the performance of multiple maximal and supramaximal surges in intensity can affect how athletes fatigue during a race and influence training strategies that can lead to success in these races.

13.
BMJ Open ; 14(6): e081933, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866577

RESUMO

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.


Assuntos
Artéria Hepática , Transplante de Fígado , Complicações Pós-Operatórias , Sistema de Registros , Trombose , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Criança , Incidência , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Trombose/etiologia , Trombose/epidemiologia , Adolescente , Pré-Escolar , Feminino , Masculino , Constrição Patológica/etiologia , Lactente , Estudos Multicêntricos como Assunto
14.
Antioxidants (Basel) ; 13(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38929112

RESUMO

Considering the high frequency of malignant breast tumors, there is a growing search for new therapeutic strategies that control neoplastic growth and dissemination, combined with fewer adverse reactions. Therefore, this study evaluated the effects of ozone therapy in female dogs with mammary cancer undergoing chemotherapy treatment. Twenty-five canines diagnosed with malignant mammary neoplasia were divided into two groups: one treated with carboplatin alone (n = 11) and the other with carboplatin associated with ozone therapy (n = 14). Clinical and laboratory evaluations, mastectomy, analysis of the oxidative profile based on total antioxidant capacity (TAC) and serum concentrations of malondialdehyde (MDA), survival rate, and quality of life were performed. Animals in the ozone therapy group had higher concentrations of red blood cells and platelets, significantly improving the survival rate and quality of life. Furthermore, adverse reactions were less intense and frequent in this group, which was associated with an increase in TAC and a reduction in MDA. These results indicate that the combination of carboplatin and ozone therapy represents a promising complementary treatment for female dogs with mammary cancer, as it was associated with fewer adverse reactions and a better oxidative profile.

15.
Animals (Basel) ; 14(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38929385

RESUMO

Monitoring weight development is essential for decision-making and assessing the effectiveness of management strategies. However, this practice is often hindered by the lack of scales on farms. This study aimed to characterize the weight development and growth curves of male and female Santa Inês lambs from birth to weaning, managed on pasture with creep-fed concentrate supplementation. Data from 212 lambs during the pre-weaning phase were analyzed. The animals were weighed every seven days to evaluate total weight gain and average daily gain. Biometric measurements were taken every 28 days. Mixed models were used to assess the effects of sex and birth type on birth and weaning weights. Simple and multiple linear regression models were employed to estimate live weight using biometric measurements. The non-linear Gompertz model was utilized to describe weight development and formulate growth curves. Results were considered significant at p < 0.05. An interaction effect between birth type and sex (p < 0.05) was noted for birth weight, with the lowest weight observed in twin-birth females (2.96 kg) and the highest in single-birth males (3.73 kg) and females (3.65 kg) (p > 0.05). Birth type significantly influenced average daily gain, total weight gain, and weaning weight (p < 0.05). The Gompertz model accurately depicted the growth curves, effectively describing the weight development. Pearson's correlation coefficients between biometric measurements and weight were positive and significant (p < 0.05), ranging from 0.599 for hip height to 0.847 for heart girth. Consequently, the simple and multiple regression equations demonstrated high precision in predicting weaning weight. In conclusion, twin-birth lambs receiving concentrate supplementation via creep-feeding and managed on pasture showed different developmental patterns compared to single-birth lambs under the same conditions. The Gompertz model proved effective for monitoring development during the pre-weaning phase. All simple and multiple linear regression models were effective in predicting weaning weight through biometric measurements. However, for practical application, the model incorporating two measurements-body length and abdominal circumference-is recommended.

16.
Rev Bras Ortop (Sao Paulo) ; 59(3): e403-e408, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911893

RESUMO

Objective Complex regional pain syndrome (CRPS) requires further understanding. Thus, the present study aimed to analyze if pre- and intraoperative factors may be related to the development of CRPS in the postoperative period. Methods We reviewed 1,183 medical records of patients undergoing forearm and hand surgeries from 2015 to 2021. The data of interest, that is, diagnosis, incisions, synthesis material, and anesthesia, were collected, tabulated, and statistically analyzed, with subsequent calculation of the odds ratios. Results Most patients were female, aged between 30 and 59 years, and sought the service electively (67% of the cases). The diagnoses included soft tissue trauma (43%), bone trauma (31.6%), and compressive syndromes (25.5%). During this period, 45 (3.8%) subjects developed CRPS. The statistical analysis showed that the chance of developing CRPS is twice as high in patients with compressive syndrome, especially carpal tunnel syndrome (CTS), which represented most surgeries performed in our service (24%). Two or more incisions occurred in 7.6% of the cases, which tripled the chance of developing postoperative CRPS. Gender, age, use pf synthetic material, type of anesthesia type did not statistically increase the risk of developing postoperative CRPS. Conclusion In short, the incidence of CRPS is low; however, it is critical to know and recognize the risk factors for prevention and active screening in the postoperative period.

17.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891851

RESUMO

Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , MicroRNAs , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminúria/genética , Biomarcadores/análise , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Regulação para Baixo/genética , Taxa de Filtração Glomerular , MicroRNAs/genética , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo
18.
Eur J Pharmacol ; 977: 176723, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38851560

RESUMO

Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool) , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Apoptose/efeitos dos fármacos
19.
Future Microbiol ; 19(8): 667-679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38864708

RESUMO

Aim: The present study investigated the antimicrobial effectiveness of a rhamnolipid complexed with arginine (RLMIX_Arg) against planktonic cells and biofilms of methicillin-resistant Staphylococcus aureus (MRSA). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol: M07-A10, checkerboard test, biofilm in plates and catheters and flow cytometry were used. Result: RLMIX_Arg has bactericidal and synergistic activity with oxacillin. RLMIX_Arg inhibits the formation of MRSA biofilms on plates at sub-inhibitory concentrations and has antibiofilm action against MRSA in peripheral venous catheters. Catheters impregnated with RLMIX_Arg reduce the formation of MRSA biofilms. Conclusion: RLMIX_Arg exhibits potential for application in preventing infections related to methicillin-resistant S. aureus biofilms.


[Box: see text].


Assuntos
Antibacterianos , Arginina , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Tensoativos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Arginina/farmacologia , Arginina/química , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Tensoativos/farmacologia , Tensoativos/química , Glicolipídeos/farmacologia , Glicolipídeos/química , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Oxacilina/farmacologia , Sinergismo Farmacológico
20.
Artigo em Inglês | MEDLINE | ID: mdl-38830052

RESUMO

Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.

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