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1.
World J Urol ; 42(1): 365, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822877

RESUMO

AIM: This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention. MATERIALS AND METHODS: Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment. RESULTS: All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively. CONCLUSION: Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Hiperplasia Prostática , Tansulosina , Humanos , Tansulosina/administração & dosagem , Tansulosina/uso terapêutico , Masculino , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Esquema de Medicação
2.
Foot Ankle Int ; : 10711007241255381, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872312

RESUMO

BACKGROUND: The management of failed total ankle replacements, with significant loss of bone stock, is challenging with high rates of complications and associated morbidity. Recent technological advances have enabled the development of patient-customized 3D-printed titanium truss arthrodesis implants, which offer an alternative salvage option for failed total ankle replacements. METHODS: A prospective observational study was performed of 6 cases of failed total ankle replacements that were managed using custom patient-specific 3D-printed titanium truss arthrodesis implants. Technical tips, classification, and a treatment algorithm were developed based on our initial experience. RESULTS: Between November 2018 and March 2022, 6 patients underwent arthrodesis for failed total ankle replacements. Follow-up was available for all cases. The mean follow-up was 3.0 years (range 1-4.5). The mean MOXFQ Index improved from 73.1 to 32.3 (P < .05). The mean EQ-5D-5L Index improved from 0.366 to 0.743 (P < .05) and the EQ-VAS also improved from 53.0 to 63.3 (P = .36). The mean VAS-Pain score at final follow-up was 27.5. There were no cases of nonunion. None of the patients were smokers. The overall complication rate was 50%. Two patients returned to surgery: one for wound washout following TAR explantation and a second for removal of metalwork 2 years following surgery for a prosthetic joint infection secondary to hematogenous spread. No patients underwent revision fixation or amputation. CONCLUSION: Custom patient-specific 3D-printed titanium truss arthrodesis implants are a viable treatment option for failed total ankle replacements.

3.
Open Vet J ; 14(3): 814-821, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38682130

RESUMO

Background: Over the past decades, Capparis spinosa has been considered a traditional therapy for relieving different illnesses. Mastitis causes a decrease in milk production and is usually treated with injectable and intra-mammary antibiotics. Aim: Investigating the therapeutic effects of C. spinosa root extract on subclinically mastitic ewes. Methods: Totally, 164 lactating ewes were selected randomly from the flocks that existed in some areas belonging to Al-Najaf City (Najaf, Iraq) from September to December (2022). Each study animal was subjected to direct sampling of milk before and once each week for 6 weeks (42 days) post treatment to be tested directly by the California mastitis test (CMT). Results: Concerning phytochemical testing of ethanolic root extract, the findings revealed a significant increase in the concentration of alkaloids, flavonoids, polyphenols, and tannins when compared to other components such as coumarins, saponin, glycosides, amino acids, and steroids. In this study, there were 44.51% infected ewes with subclinical mastitis, involving 25.61%, 13.41%, and 5.49% for scores 1, 2, and 3, respectively. In comparison with pre-treatment week, insignificant alteration was seen in the values of all scores in therapeutic week 1. However, significant differences were initiated in values of score 0 in week 2; score 0 and score 2 in week 3; score 0, score 1, and score 2 in week 4; and values of all scores in weeks 5 and 6. Conclusion: This represents the first Iraqi study aimed at the treatment of subclinical mastitis in sheep using the root extract of C. spinosa. Phytochemical testing of ethanolic extract revealed the presence of variable amounts of chemical compounds that reflect their effects on treated animals by decreasing the number of infected ewes with the disease. Moreover, studies are greatly important to estimate the therapeutic effects of other parts of C. spinosa such as leaves and seeds, on the disease and other animal diseases.


Assuntos
Capparis , Mastite , Extratos Vegetais , Raízes de Plantas , Doenças dos Ovinos , Animais , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Feminino , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Raízes de Plantas/química , Mastite/veterinária , Mastite/tratamento farmacológico , Capparis/química , Leite/química
4.
Cancers (Basel) ; 15(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37345173

RESUMO

In the field of medical imaging, deep learning has made considerable strides, particularly in the diagnosis of brain tumors. The Internet of Medical Things (IoMT) has made it possible to combine these deep learning models into advanced medical devices for more accurate and efficient diagnosis. Convolutional neural networks (CNNs) are a popular deep learning technique for brain tumor detection because they can be trained on vast medical imaging datasets to recognize cancers in new images. Despite its benefits, which include greater accuracy and efficiency, deep learning has disadvantages, such as high computing costs and the possibility of skewed findings due to inadequate training data. Further study is needed to fully understand the potential and limitations of deep learning in brain tumor detection in the IoMT and to overcome the obstacles associated with real-world implementation. In this study, we propose a new CNN-based deep learning model for brain tumor detection. The suggested model is an end-to-end model, which reduces the system's complexity in comparison to earlier deep learning models. In addition, our model is lightweight, as it is built from a small number of layers compared to other previous models, which makes the model suitable for real-time applications. The optimistic findings of a rapid increase in accuracy (99.48% for binary class and 96.86% for multi-class) demonstrate that the new framework model has excelled in the competition. This study demonstrates that the suggested deep model outperforms other CNNs for detecting brain tumors. Additionally, the study provides a framework for secure data transfer of medical lab results with security recommendations to ensure security in the IoMT.

5.
Molecules ; 28(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36677683

RESUMO

Hybrid compounds of flavones, namely chrysin and kaempferol, and substituted 1,2,3-triazole derivatives, were synthesized by click reaction of the intermediate O-propargyl derivatives. 4-Fluoro- and 4-nitrobenzyl-1,2,3-triazole-containing hybrid molecules were prepared. The mono- and bis-coupled hybrids were investigated on 60 cell lines of 9 common cancer types (NCI60) in vitro as antitumor agents. Some of them proved to have a significant antiproliferative effect.


Assuntos
Antineoplásicos , Flavonas , Relação Estrutura-Atividade , Proliferação de Células , Triazóis/farmacologia , Antineoplásicos/farmacologia , Flavonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Linhagem Celular Tumoral
6.
Stem Cell Rev Rep ; 19(3): 817-822, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36376770

RESUMO

OBJECTIVE: We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. METHODS: Eight male patients (age 62 ± 2.4 years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. RESULTS: No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6 months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. CONCLUSIONS: Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.


Assuntos
Cardiomiopatias , Cardiopatias , Isquemia Miocárdica , Humanos , Masculino , Pessoa de Meia-Idade , Lasers , Isquemia Miocárdica/cirurgia , Revascularização Miocárdica/métodos , Resultado do Tratamento
7.
Stem Cell Rev Rep ; 19(2): 573-577, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36271311

RESUMO

BACKGROUND: Ischemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year. METHODS: Here, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies. RESULTS: At 1 day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4 weeks after AMI. CONCLUSIONS: The use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Infarto do Miocárdio , Camundongos , Animais , Humanos , Miócitos Cardíacos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Mesenquimais/metabolismo , Apoptose , Isquemia/metabolismo
8.
Ann Surg ; 275(3): 617-620, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511125

RESUMO

OBJECTIVE: To describe the quality of operative performance feedback using evaluation tools commonly used by general surgery residency training programs. SUMMARY OF BACKGROUND DATA: The majority of surgical training programs administer an evaluation through which faculty members may rate and comment on trainee operative performance at the end of the rotation (EOR). Many programs have also implemented the system for improving and measuring procedural learning (SIMPL), a workplace-based assessment tool with which faculty can rate and comment on a trainee's operative performance immediately after a case. It is unknown how the quality of narrative operative performance feedback delivered with these tools compares. METHODS: The authors collected EOR evaluations and SIMPL narrative comments on trainees' operative performance from 3 university-based surgery training programs during the 2016-2017 academic year. Two surgeon raters categorized comments relating to operative skills as being specific or general and as encouraging and/or corrective. Comments were then classified as effective, mediocre, ineffective, or irrelevant. The frequencies with which comments were rated as effective were compared using Chi-square analysis. RESULTS: The authors analyzed a total of 600 comments. 10.7% of EOR and 58.3% of SIMPL operative performance evaluation comments were deemed effective (P < 0.0001). CONCLUSIONS: Evaluators give significantly higher quality operative performance feedback when using workplace-based assessment tools rather than EOR evaluations.


Assuntos
Competência Clínica , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência , Procedimentos Cirúrgicos Operatórios/educação , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Estudos Retrospectivos
10.
Stem Cell Res Ther ; 12(1): 469, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419143

RESUMO

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.


Assuntos
Tratamento Farmacológico da COVID-19 , Exossomos , Transplante de Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais
11.
Foot (Edinb) ; 48: 101850, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390947

RESUMO

INTRODUCTION: The safety of resuming elective surgical services remains unclear following several surges of the COVID-19 pandemic worldwide. Multiple studies have reported high rates of post-operative mortality and pulmonary complications. 30-day outcomes on an initial cohort of patients undergoing elective foot and ankle surgery at 3 central London hospitals are presented. MATERIALS AND METHODS: This study is a retrospective review of the first 63 patients undergoing surgery following the first UK surge via a modified treatment pathway, based on published national guidelines, designed to minimise the risks to patients and staff associated with COVID-19. RESULTS: 90% of patients were ASA 1 or 2, with an average age of 46. All tested negative for COVID-19 pre-operatively and all but one underwent a general anaesthetic. 10 patients required one night hospital stays and 1 was admitted for four nights. 52 were day case procedures. 2 complications were identified, not relating to COVID-19 infection. No 30-day mortalities or pulmonary complications were recorded. CONCLUSIONS: With a community prevalence of COVID-19 of between 1 in 1500 and 1 in 1700, elective foot and ankle surgery was safe following the first surge of the pandemic in the UK. This data can guide elective service planning in countries with pandemic curves behind the UK's or in the event of further surges in national cases.


Assuntos
Tornozelo/cirurgia , COVID-19/epidemiologia , Procedimentos Cirúrgicos Eletivos , Pé/cirurgia , Segurança do Paciente , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , SARS-CoV-2
12.
Sci Prog ; 104(3): 368504211033703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293965

RESUMO

Potassium bromate (KBrO3) is classified by the International Agency for Research on Cancer as a carcinogenic compound, where it causes renal tumors. The present study investigated the potential curative effect of metformin loaded on gold nanoparticles (MET AuNPs) in attenuating KBrO3-induced nephrotoxicity. Rats were divided into eight groups (control, MET, AuNPs, MET AuNPs, KBrO3, KBrO3/MET, KBrO3/AuNPS, and KBrO3/MET AuNPs). KBrO3 administration resulted in a significant elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), total bilirubin (TB), direct bilirubin (DB), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, urea, uric acid. Also, KBrO3 significantly increased renal malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) levels and reduced the activities of antioxidant molecules superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and Reduced glutathione (GSH). It also caused damaged DNA spots in comet assay and increased inflammatory IL-6 and apoptotic markers (caspase 3, Bax) while antiapoptotic Bcl-2 was significantly reduced. MET, AuNPS, MET AuNPS reduced the extent of renal damage induced by KBrO3 as indicated by decreased (AST, ALT, ALP, Alb, TP, TB, DB, creatinine, urea, uric, Lipid profile). MET, AuNPS, MET AuNPS showed a good curative effect against KBrO3-induced nephrotoxicity and MET AuNPS group showed better results compared with monotherapy.


Assuntos
Nanopartículas Metálicas , Metformina , Animais , Bilirrubina/metabolismo , Bilirrubina/farmacologia , Bromatos , Colesterol/metabolismo , Colesterol/farmacologia , Creatinina/metabolismo , Creatinina/farmacologia , Ouro/metabolismo , Ouro/farmacologia , Fígado , Nanopartículas Metálicas/toxicidade , Metformina/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Ratos , Ureia/metabolismo , Ureia/farmacologia
13.
Lupus Sci Med ; 8(1)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952624

RESUMO

OBJECTIVES: Cardiovascular complications became a notable cause of morbidity and mortality in patients with lupus as therapeutic advancements became more efficient at managing other complications. The Appalachian community in Kentucky has a higher prevalence of traditional cardiovascular risk factors, predisposing them to cardiovascular events. Namely, the mean body mass index of the members of the Kentucky Appalachian community was reported at 33 kg/m2 and 94.3% of male members of this community use tobacco. We sought to identify risk factors that predispose patients with lupus to cardiovascular morbidities and examine the effect of immunomodulatory drugs. METHODS: We identified 20 UKHS patients having both a lupus diagnosis and experienced at least one cardiovascular event. We chose three controls matched for birth-year ±5 years to each case. In a case-control design, we analysed lupus manifestations, cardiovascular risk factors and immunosuppressive therapies. We collected Systemic Lupus Erythematosus Disease Activity Index 2000 disease activity index during the cardiovascular event. RESULTS: We identified 308 patients with lupus from among all University of Kentucky Health System patients. 20 (6.5%) of such patients with lupus were confirmed to cardiovascular complication. Of those 20, 7 (35%) had experienced myocardial infarction, 10 (50%) had experienced stroke and 4 (20%) had peripheral ischaemia. Tobacco use and male gender were the only traditional cardiovascular risk factors higher in the cases group. Hydroxychloroquine and steroids were less utilised in the cases than in the controls (70% vs 100% in hydroxychloroquine, 30% vs 82% in steroids). Venous thrombosis was found to be significantly higher in the cases. On multivariate analysis, venous thrombosis remained significant. CONCLUSION: Despite tobacco use partially explaining the increased risk of cardiovascular disease among the cases group, the higher prevalence of venous thrombosis in the cases group suggests lupus as a potential additional risk factor of cardiovascular morbidity among patients with lupus in this Appalachian community.


Assuntos
Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Região dos Apalaches , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Hidroxicloroquina , Kentucky/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Fatores de Risco
14.
Can J Cardiol ; 37(10): 1593-1606, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33838228

RESUMO

BACKGROUND: Downregulation of claudin-5 in the heart is associated with the end-stage heart failure. However, the underlying mechanism ofclaudin-5 is unclear. Here we investigated the molecular actions of claudin-5 in perspective of mitochondria in cardiomyocytes to better understand the role of claudin-5 in cardioprotection during ischemia. METHODS: Myocardial ischemia/reperfusion (I/R; 30 min/24 h) and hypoxia/reoxygenation (H/R; 24 h/4 h) were used in this study. Confocal microscopy and transmission electron microscope (TEM) were used to observe mitochondrial morphology. RESULTS: Claudin-5 was detected in murine heart tissue and neonatal rat cardiomyocytes (NRCM). Its protein level was severely decreased after myocardial I/R or H/R. Confocal microscopy showedclaudin-5 presented in the mitochondria of NRCM. H/R-induced claudin-5 downregulation was accompanied by mitochondrial fragmentation. The mitofusin 2 (Mfn2) expressionwas dramatically decreased while the dynamin-related protein (Drp) 1 expression was significantly increased after H/R. The TEM indicatedH/R-induced mitochondrial swelling and fission. Adenoviral claudin-5 overexpression reversed these structural disintegration of mitochondria. The mitochondria-centered intrinsic pathway of apoptosis triggered by H/R and indicated by the cytochrome c and cleaved caspase 3 in the cytoplasm of NRCMs was also reduced by overexpressing claudin-5. Claudin-5 overexpression in mouse heart also significantly decreased cleaved caspase 3 and the infarct size in ischemic heart with improved systolic function. CONCLUSION: We demonstrated for the first time the presence of claudin-5 in the mitochondria in cardiomyocytes and provided the firm evidence for the cardioprotective role of claudin-5 in the preservation of mitochondrial dynamics and cell fate against hypoxia- or ischemia-induced stress.


Assuntos
Claudina-5/genética , Hipóxia/prevenção & controle , Mitocôndrias Cardíacas/genética , Dinâmica Mitocondrial/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Células Cultivadas , Claudina-5/biossíntese , Dinaminas/biossíntese , Dinaminas/genética , GTP Fosfo-Hidrolases/biossíntese , GTP Fosfo-Hidrolases/genética , Hipóxia/genética , Hipóxia/patologia , Proteínas de Membrana , Microscopia Eletrônica de Transmissão , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/ultraestrutura , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/ultraestrutura , Ratos , Ratos Sprague-Dawley
15.
Int J Mol Sci ; 22(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530466

RESUMO

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Cardiopatias/terapia , Animais , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/metabolismo , Regeneração , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Células-Tronco/metabolismo , Resultado do Tratamento , Cicatrização
16.
Leukemia ; 35(9): 2658-2671, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33623143

RESUMO

Like their homing after transplantation to bone marrow (BM), the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not fully understood, and several overlapping pathways are involved. Several years ago our group proposed that sterile inflammation in the BM microenvironment induced by pro-mobilizing agents is a driving force in this process. In favor of our proposal, both complement cascade (ComC)-deficient and Nlrp3 inflammasome-deficient mice are poor G-CSF and AMD3100 mobilizers. It is also known that the Nlrp3 inflammasome mediates its effects by activating caspase-1, which is responsible for proteolytic activation of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) and their release from cells along with several danger-associated molecular pattern molecules (DAMPs). We observed in the past that IL-1ß and IL-18 independently promote mobilization of HSPCs. In the current work we demonstrated that caspase-1-KO mice are poor mobilizers, and, to our surprise, administration of IL-1ß or IL-18, as in the case of Nlrp3-KO animals, does not correct this defect. Moreover, neither Caspase-1-KO nor Nlrp3-KO mice properly activated the ComC to execute the mobilization process. Interestingly, mobilization in these animals and activation of the ComC were both restored after injection of the DAMP cocktail eATP+HGMB1+S100A9, the components of which are normally released from cells in an Nlrp3 inflammasome-caspase-1-dependent manner. In addition, we report that caspase-1-deficient HSPCs show a decrease in migration in response to BM homing factors and engraft more poorly after transplantation. These results for the first time identify caspase-1 as an orchestrator of HSPC trafficking.


Assuntos
Alarminas/metabolismo , Caspase 1/fisiologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Inflamação/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Animais , Movimento Celular , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Inflamassomos/metabolismo , Inflamação/metabolismo , Inflamação/terapia , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
17.
BMJ Case Rep ; 14(1)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504515

RESUMO

A 39-year-old multiparous Afro-Caribbean woman attended the emergency department with sudden-onset severe right iliac fossa pain. Her inflammatory markers were mildly elevated. Computerised tomography of the abdomen demonstrated features of fat stranding in the right iliac fossa suspicious of acute appendicitis. The scan also noted uterine leiomyomas. The patient was taken to theatre for an emergency diagnostic laparoscopy where her appendix was found to be macroscopically normal. A necrotic heavily calcified parasitic leiomyoma was seen in the right adnexa, free of the uterus and adherent to the greater omentum on a long torted pedicle. The parasitic leiomyoma was successfully removed piecemeal laparoscopically. Complications of leiomyomas, namely, torsion and necrosis, are important differentials in women presenting with sudden-onset lower abdominal pain. A history of sudden-onset severe lower abdominal pain with a background of known leiomyoma should prompt the clerking surgeon to consider a complication of leiomyoma as part of the differential diagnoses.


Assuntos
Calcinose/diagnóstico por imagem , Leiomioma/diagnóstico por imagem , Anormalidade Torcional/diagnóstico por imagem , Neoplasias Uterinas/diagnóstico por imagem , Dor Abdominal/etiologia , Adulto , Apendicite/diagnóstico , Cesárea , Diagnóstico Diferencial , Feminino , Humanos , Laparoscopia , Leiomioma/cirurgia , Inoculação de Neoplasia , Omento , Tomografia Computadorizada por Raios X , Anormalidade Torcional/complicações , Anormalidade Torcional/cirurgia , Neoplasias Uterinas/cirurgia
18.
World J Urol ; 39(8): 3089-3093, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33471164

RESUMO

PURPOSE: The safety and efficacy of early second session shock wave lithotripsy (SWL) compared with laser ureteroscopy (URS) for the treatment of upper ureteric stones were evaluated. METHODS: From January to October 2019, 108 patients with upper ureteric stones (< 1.5 cm and ≤ 1000 Hounsfield unit (HU)) were randomized into SWL and laser URS groups. The second SWL session was performed within 48-72 h of the first session. Using plain abdominal X-ray and ultrasonography, patients were evaluated 48-72 h after the first SWL session and one week after the second and third SWL sessions or one week after URS. The procedure was considered a success when no additional procedures were needed to clear the stone. To determine the stone-free rate (SFR), noncontrast computed tomography of the urinary tract was performed three months postoperatively. RESULTS: In the SWL group, the success rates were 92.6% and 94.4% after the second and third sessions. The SFR was 96.2% in the laser URS group. The success rates were not significantly different between the second and third SWL sessions versus the laser URS (p = 0.418 and 0.660, respectively). Operative and fluoroscopy times were significantly longer in the SWL group (p = 0.001), and JJ stent insertions were needed after laser URS. CONCLUSION: Ultraslow full-power SWL treatment of patients with upper ureteric stones (< 1.5 cm and ≤ 1000 HU) with an early second session is safe and effective compared to laser URS. Patients who do not respond to early second SWL session should be shifted to another treatment modality.


Assuntos
Ondas de Choque de Alta Energia/uso terapêutico , Litotripsia , Retratamento/métodos , Cálculos Ureterais , Ureteroscopia , Feminino , Humanos , Litotripsia/efeitos adversos , Litotripsia/instrumentação , Litotripsia/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Radiografia Abdominal/métodos , Tempo para o Tratamento , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Resultado do Tratamento , Ultrassonografia/métodos , Cálculos Ureterais/diagnóstico , Cálculos Ureterais/terapia , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos
19.
J Biomed Mater Res A ; 109(3): 326-335, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32491263

RESUMO

Gelatin coatings are effective in increasing the retention of MSCs injected into the heart and minimizing the damage from acute myocardial infarction (AMI), but early studies suffered from low fractions of the MSCs coated with gelatin. Biotinylation of the MSC surface is a critical first step in the gelatin coating process, and in this study, we evaluated the use of biotinylated cholesterol "lipid insertion" anchors as a substitute for the covalent NHS-biotin anchors to the cell surface. Streptavidin-eosin molecules, where eosin is our photoinitiator, can then be bound to the cell surface through biotin-streptavidin affinity. The use of cholesterol anchors increased streptavidin density on the surface of MSCs further driving polymerization and allowing for an increased fraction of MSCs coated with gelatin (83%) when compared to NHS-biotin (52%). Additionally, the cholesterol anchors increased the uniformity of the coating on the MSC surface and supported greater numbers of coated MSCs even when the streptavidin density was slightly lower than that of an NHS-biotin anchoring strategy. Critically, this improvement in gelatin coating efficiency did not impact cytokine secretion and other critical MSC functions. Proper selection of the cholesterol anchor and the biotinylation conditions supports cellular function and densities of streptavidin on the MSC surface of up to ~105 streptavidin molecules/µm2 . In all, these cholesterol anchors offer an effective path towards the formation of conformal coatings on the majority of MSCs to improve the retention of MSCs in the heart following AMI.


Assuntos
Células Imobilizadas/química , Colesterol/química , Gelatina/química , Células-Tronco Mesenquimais/química , Animais , Materiais Biocompatíveis/química , Células Cultivadas , Células Imobilizadas/citologia , Células Imobilizadas/transplante , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/terapia
20.
Comput Intell Neurosci ; 2021: 6342226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992648

RESUMO

Ovarian cancer is the third most common gynecologic cancers worldwide. Advanced ovarian cancer patients bear a significant mortality rate. Survival estimation is essential for clinicians and patients to understand better and tolerate future outcomes. The present study intends to investigate different survival predictors available for cancer prognosis using data mining techniques. Dataset of 140 advanced ovarian cancer patients containing data from different data profiles (clinical, treatment, and overall life quality) has been collected and used to foresee cancer patients' survival. Attributes from each data profile have been processed accordingly. Clinical data has been prepared corresponding to missing values and outliers. Treatment data including varying time periods were created using sequence mining techniques to identify the treatments given to the patients. And lastly, different comorbidities were combined into a single factor by computing Charlson Comorbidity Index for each patient. After appropriate preprocessing, the integrated dataset is classified using appropriate machine learning algorithms. The proposed integrated model approach gave the highest accuracy of 76.4% using ensemble technique with sequential pattern mining including time intervals of 2 months between treatments. Thus, the treatment sequences and, most importantly, life quality attributes significantly contribute to the survival prediction of cancer patients.


Assuntos
Mineração de Dados , Neoplasias , Algoritmos , Feminino , Humanos , Aprendizado de Máquina
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