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1.
Chem Biodivers ; 21(2): e202301560, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38251927

RESUMO

Several infectious diseases are transmitted and spread by mosquitoes, and millions of people die annually from them. The mosquito, Culex pipiens is a responsible for the emergence of various Virus in Egypt. So, we devote our work to evaluate the larvicidal efficacy against C. pipiens of some new heterocyclic compounds containing chlorine motifs. The implementation was emanated from using 2-cyano-N'-(2-(2,4-dichlorophenoxy)acetyl)acetohydrazide (3) as scaffold to synthesize some new heterocyclic compounds. The structures of the synthesized compounds were interpreted scrupulously by spectroscopic and elemental analyses. Thereafter, the larvicidal activity against C. pipiens of thirteen synthesized compounds was estimated. Noteworthy, cyanoacetohydrazide derivative 3 and 3-iminobenzochromene derivative 12 showed a fabulous potent efficacy with LC50 equal to 3.2 and 3.5 ppm against C. pipiens, respectively, and are worth being further evaluated in the field of pest control.


Assuntos
Culex , Compostos Heterocíclicos , Hidrazinas , Inseticidas , Humanos , Animais , Inseticidas/farmacologia , Inseticidas/química , Larva , Compostos Heterocíclicos/farmacologia , Extratos Vegetais/química
2.
Arch Pharm (Weinheim) ; 357(9): e2400217, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38864845

RESUMO

A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl-2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-4-carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[b]thiophene candidates (2-14). Interestingly, compound 14 showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC50 = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC50 = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound 3 could exhibit the best inhibitory potential among the investigated candidates (IC50 = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC50 = 28.34 nM) and doxorubicin (IC50 = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound 14 could display the best binding affinity with an IC50 value of 77.82 µM in comparison to doxorubicin (IC50 = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound 3 prompts the G1 phase arrest in michigan cancer foundation-7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.


Assuntos
Antineoplásicos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Substâncias Intercalantes , Tiofenos , Inibidores da Topoisomerase I , Inibidores da Topoisomerase II , Humanos , Tiofenos/farmacologia , Tiofenos/síntese química , Tiofenos/química , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Relação Estrutura-Atividade , Substâncias Intercalantes/farmacologia , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Estrutura Molecular , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Apoptose/efeitos dos fármacos , DNA , DNA Topoisomerases Tipo I/metabolismo , Farmacóforo
3.
Chem Biodivers ; 20(7): e202300706, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37321977

RESUMO

N'-[(4-Chloro-2-oxo-2H-chromen-3-yl)methylene]-2-cyanoacetohydrazide (3) was synthesized in excellent yield from the condensation of 4-Chloro-2-oxo-2H-chromene-3-carbaldehyde with cyanoacetohydrazide. Compound 3 was utilized as a building block to synthesize novel coumarin and heterocycle-fused coumarin derivatives. The chemical structures of all the new coumarin compounds were identified by spectral analyses. Some of the new coumarins compounds were screened in human cancer cell lines (HEPG-2, MCF-7, HCT-116 and PC-3) to learn about their cytotoxic effects in addition to the study of their DNA damage and antioxidant activity. Three of these compounds exhibited remarkable antioxidant and anti-proliferative activities. Moreover, they have the capability to protect DNA from damage induced by bleomycin. Molecular docking, DFT and molecular electrostatic potential studies were performed on the compounds in vitro.


Assuntos
Antineoplásicos , Antioxidantes , Humanos , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Linhagem Celular , Cumarínicos/química , Antineoplásicos/química , Relação Estrutura-Atividade
4.
Inflammopharmacology ; 31(6): 3127-3142, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37526838

RESUMO

Methotrexate (MTX) and diacerein (DIA) are two of the most potent disease-modifying anti-rheumatic drugs used for the treatment of rheumatoid arthritis (RA). DIA has reflected some GIT and hepatobiliary manifestations in numerous cases. It undergoes biotransformation in the liver into the active metabolite rhein (RH) which is characterized by its excellent anti-inflammatory activity and lower side effects. However, RH's hydrophobic nature and low bioavailability do not encourage its use in RA. The current study aims to use RH in combination with MTX in targeted solid lipid nanoparticles (RH-MTX-SLNs) for better effectiveness and shadowing light on its possible mechanistic pathways. RH-MTX-SLNs were prepared and assessed for their quality attributes. The effect of the formulation was assessed in-vivo in an adjuvant arthritis animal model investigating the role of the endoplasmic reticulum stress (ERS)-induced apoptosis. Results revealed that RH-MTX-SLNs were in the suitable nanosized range with high negative zeta potential indicating good stability. In-vivo, RH-MTX-SLNs significantly improved all measured inflammatory and arthritic markers, confirmed by electron microscopy and histology examination of the joints. Besides, the formulation was able to alter the ERS-mediated apoptosis. In conclusion, RH-MTX-SLNs can represent a promising therapeutic approach for RA showing significant anti-arthritic activity.


Assuntos
Antirreumáticos , Artrite Experimental , Artrite Reumatoide , Nanopartículas , Animais , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Artrite Experimental/metabolismo , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/metabolismo
5.
J Pediatr Orthop ; 42(7): e703-e708, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816676

RESUMO

BACKGROUND: The choice between growth-sparing techniques or definitive spine fusion for severe idiopathic early-onset scoliosis (IEOS) in skeletally immature patients aged 8 to 10 years represents a challenging dilemma. Although growth-sparing techniques show high complication rates in severe IEOS, the outcomes of definitive fusion in borderline skeletally immature patients with severe IEOS have not been investigated. We aimed to investigate the outcomes of early definitive fusion using all-pedicle-screw constructs in skeletally immature patients aged 8 to 10 years with severe IEOS. METHODS: The inclusion criteria were as follows: IEOS, age 8 years or above, major coronal curve ≥90 degrees, thoracic height >18 cm, no history of previous spine surgery, no intraspinal anomalies and at least 3 years of postoperative follow-up. Patients underwent instrumented spinal fusion with all-pedicle-screw constructs and multiple Ponte osteotomies. All patients completed the Scoliosis Research Society 22 revision (Arabic version) questionnaire and Body Image Disturbance Questionnaire-Scoliosis version (BIDQ-S) preoperatively and at the last follow-up. RESULTS: Fifty-five patients (24 males, 31 females; mean age: 8.96 y; range: 8 to 10 y) with severe IEOS met the inclusion criteria (mean follow-up period: 4.1±0.6 y; range: 3 to 5 y). The mean major coronal Cobb angle improved significantly (P<0.001) from 107±12.5 degrees to 26.8±6.8 degrees. Mean thoracic kyphosis improved significantly (P<0.001) from 57.2±15.8 degrees to 31.2±4.4 degrees. The loss of correction at the latest follow-up was nonsignificant. The total Scoliosis Research Society 22 revision (SRS-22r) score improved significantly from 2.5±1 to 4.3±0.7. The mean BIDQ-S score improved significantly from 4.1±0.3 to 1.6±0.3. The immediate postoperative gains in the mean thoracic height (T1-T12) and spinal height (T1-S1) were 14.9% and 19.6%, respectively, and the overall height increase at the latest follow-up was 17.8% and 23.8%, respectively. One patient underwent revision for implant failure (rod breakage). CONCLUSION: Early definitive fusion for skeletally immature patients with severe IEOS yielded excellent correction with major improvements in patient quality of life. Severe IEOS poses a significant risk, but definitive fusion can potentially mitigate that risk in patients aged 8 to 10 years.


Assuntos
Escoliose , Fusão Vertebral , Criança , Feminino , Seguimentos , Humanos , Cifose/etiologia , Cifose/cirurgia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/etiologia , Escoliose/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Resultado do Tratamento
6.
Surg Innov ; 29(1): 56-65, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33914655

RESUMO

Background: Endoscopic treatment can represent a technical challenge for several special situations, such as resecting gastric tumors with larger size or in unfavorable sites and performing endoscopic retrograde cholangiopancreatography (ERCP) after Roux-en-Y gastric bypass (RYGB). This study aims to describe an innovative and multipurpose technique, intragastric single-port surgery (IGS), which can be applied for abovementioned special situations and for assessing its safety, feasibility, and efficacy. Methods: IGS technique was performed through a 2-3 cm skin incision, where the stomach wall is exteriorized and fixed to the skin. The single-port device is inserted and intragastric access is gained for laparoscopic or endoscopic instruments. Three purposes of IGS were performed: (1). gastric intraluminal lesions resection; (2). to perform ERCP after RYGB; and (3). revision of pancreaticogastric anastomosis after pylorus-preserving pancreaticoduodenectomy. Results: IGS was performed successfully in 20 patients. Ten patients underwent gastric intraluminal lesion resection, mostly for gastric gastrointestinal stromal tumors (n = 7, 70%); all pathological specimens were with negative margin, mean operation time was 102.3 ± 43.5 minutes, and mean postoperative hospital stay was 4.6 ± 1.5 days. Nine patients underwent ERCP after RYGB, cleaning of the bile duct was successful in all patients (100%), and mean operation time and mean postoperative hospital stay were 140.6 ± 46.3 minutes and 4.4 ± 2.6 days, respectively. One patient underwent pancreaticogastric anastomosis revision. There were no mortalities in our series. Conclusions: IGS is a safe, feasible, and effective technique for gastric intraluminal lesion resection and for performing ERCP after RYGB, while it has the potential for other future applications.


Assuntos
Gastrectomia , Gastropatias , Colangiopancreatografia Retrógrada Endoscópica , Difusão de Inovações , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Derivação Gástrica , Humanos , Laparoscopia , Estudos Retrospectivos , Gastropatias/cirurgia , Resultado do Tratamento
7.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35055125

RESUMO

PTH induces phosphorylation of the transcriptional coregulator NACA on serine 99 through Gαs and PKA. This leads to nuclear translocation of NACA and expression of the target gene Lrp6, encoding a coreceptor of the PTH receptor (PTH1R) necessary for full anabolic response to intermittent PTH (iPTH) treatment. We hypothesized that maintaining enough functional PTH1R/LRP6 coreceptor complexes at the plasma membrane through NACA-dependent Lrp6 transcription is important to ensure maximal response to iPTH. To test this model, we generated compound heterozygous mice in which one allele each of Naca and Lrp6 is inactivated in osteoblasts and osteocytes, using a knock-in strain with a Naca99 Ser-to-Ala mutation and an Lrp6 floxed strain (test genotype: Naca99S/A; Lrp6+/fl;OCN-Cre). Four-month-old females were injected with vehicle or 100 µg/kg PTH(1-34) once daily, 5 days a week for 4 weeks. Control mice showed significant increases in vertebral trabecular bone mass and biomechanical properties that were abolished in compound heterozygotes. Lrp6 expression was reduced in compound heterozygotes vs. controls. The iPTH treatment increased Alpl and Col1a1 mRNA levels in the control but not in the test group. These results confirm that NACA and LRP6 form part of a common genetic pathway that is necessary for the full anabolic effect of iPTH.


Assuntos
Anabolizantes/administração & dosagem , Células-Tronco Embrionárias/citologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Chaperonas Moleculares/genética , Hormônio Paratireóideo/administração & dosagem , Anabolizantes/farmacologia , Animais , Linhagem Celular , Membrana Celular/metabolismo , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Introdução de Genes , Camundongos , Chaperonas Moleculares/metabolismo , Mutagênese Sítio-Dirigida , Osteoblastos/metabolismo , Osteócitos/metabolismo , Hormônio Paratireóideo/farmacologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X
8.
J Shoulder Elbow Surg ; 29(5): 941-945, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31759877

RESUMO

BACKGROUND: The lack of external rotation and shoulder abduction as sequelae of obstetric brachial plexus palsy requires a release of the subscapularis muscle associated with tendon transfer of the internal rotator of the shoulder. The aim of this study was to present the results of a teres major transfer to the infraspinatus tendon. METHODS: This study included 20 patients (9 boys and 11 girls) with a mean age of 3 years 8 months (range, 1.5-14 years). The average follow-up time was 42 months (range, 12-48 months) to determine whether external rotation weakness and internal rotation contracture sequelae were managed by anterior release of the subscapularis and teres major tendon transfer to the infraspinatus tendon. RESULTS: We found marked improvement in shoulder abduction from 67° before surgery to 158° after surgery. We also found marked improvements in active external rotation from 8° before surgery to 85° after surgery and in passive external rotation from 0° preoperatively to 72° postoperatively. Two cases showed a loss of the last degrees of internal rotation, but this improved after physiotherapy. CONCLUSIONS: Anterior release of the subscapularis tendon with a teres major transfer to the infraspinatus tendon significantly improves shoulder function in Erb palsy patients with internal rotation contracture.


Assuntos
Neuropatias do Plexo Braquial/cirurgia , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Transferência Tendinosa/métodos , Adolescente , Neuropatias do Plexo Braquial/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Rotação , Articulação do Ombro/fisiopatologia
9.
Int Orthop ; 44(6): 1153-1157, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303792

RESUMO

PURPOSE: To investigate the union rate after lunatocapitate arthrodesis for the treatment of scaphoid nonunion advanced collapse (SNAC) wrists and to evaluate the clinical results of this technique. METHODS: We conducted a prospective study between January 2014 and July 2017. Fifteen males with painful stage III SNAC wrists (average age, 32 years, range, 20-37 years; average follow-up time, 25.2 months, range, 20-36 months) underwent scaphoid excision and lunatocapitate fusion. Lunatocapitate fusions were fixed with headless Herbert screws with K-wire fixation (retrograde direction). Radiographs, wrist range of motion, and Mayo wrist score were examined. RESULTS: All patients achieved radiographic and clinical union after lunatocapitate fusion during follow-up (average 10 months post-operatively). The flexion-extension arc was 70°, and the average Mayo wrist score was 74.3 points (eight with excellent, four with good, three with satisfactory, and one with poor result). Thirteen patients returned to work, whereas two with nonunion required surgical graft revision. Complete union was achieved at an average of 12 weeks after graft revision, with improved range of motion, and the patients returned to work with a change in their occupation. CONCLUSIONS: Lunatocapitate arthrodesis is a satisfactory therapeutic alternative to four-corner fusion for SNAC wrists.


Assuntos
Articulação do Punho/cirurgia , Adulto , Artrodese/métodos , Fios Ortopédicos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas , Dor , Estudos Prospectivos , Radiografia , Amplitude de Movimento Articular , Osso Escafoide/cirurgia , Punho , Traumatismos do Punho/cirurgia
10.
Int J Mol Sci ; 21(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707790

RESUMO

Pepper originated from the Capsicum genus, which is recognized as one of the most predominant and globally distributed genera of the Solanaceae family. It is a diverse genus, consisting of more than 31 different species including five domesticated species, Capsicum baccatum, C. annuum, C. pubescen, C. frutescens, and C. chinense. Pepper is the most widely used spice in the world and is highly valued due to its pungency and unique flavor. Pepper is a good source of provitamin A; vitamins E and C; carotenoids; and phenolic compounds such as capsaicinoids, luteolin, and quercetin. All of these compounds are associated with their antioxidant as well as other biological activities. Interestingly, Capsicum fruits have been used as food additives in the treatment of toothache, parasitic infections, coughs, wound healing, sore throat, and rheumatism. Moreover, it possesses antimicrobial, antiseptic, anticancer, counterirritant, appetite stimulator, antioxidant, and immunomodulator activities. Capsaicin and Capsicum creams are accessible in numerous ways and have been utilized in HIV-linked neuropathy and intractable pain.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Capsicum/química , Capsicum/classificação , Frutas/química , Extratos Vegetais/farmacologia , Capsicum/metabolismo , Carotenoides/análise , Flavonoides/análise , Irritantes/farmacologia , Fenóis/análise , Extratos Vegetais/química , Vitaminas/análise
11.
J Mol Cell Cardiol ; 130: 36-48, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30880250

RESUMO

AIMS: The FDA-approved histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA, Vorinostat) has been shown to induce cardiomyocyte autophagy and blunt ischemia/reperfusion (I/R) injury when administered at the time of reperfusion. However, the precise mechanisms underlying the cardioprotective activity of SAHA are unknown. Mitochondrial dysfunction and oxidative damage are major contributors to myocardial apoptosis during I/R injury. We hypothesize that SAHA protects the myocardium by maintaining mitochondrial homeostasis and reducing reactive oxygen species (ROS) production during I/R injury. METHODS: Mouse and cultured cardiomyocytes (neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes) I/R models were used to investigate the effects of SAHA on mitochondria. ATG7 knockout mice, ATG7 knockdown by siRNA and PGC-1α knockdown by adenovirus in cardiomyocytes were used to test the dependency of autophagy and PGC-1α-mediated mitochondrial biogenesis respectively. RESULTS: Intact and total mitochondrial DNA (mtDNA) content and mitochondrial mass were significantly increased in cardiomyocytes by SAHA pretreatment before simulated I/R. In vivo, I/R induced >50% loss of mtDNA content in the border zones of mouse hearts, but SAHA pretreatment and reperfusion treatment alone reverted mtDNA content and mitochondrial mass to control levels. Moreover, pretreatment of cardiomyocytes with SAHA resulted in a 4-fold decrease in I/R-induced loss of mitochondrial membrane potential and a 25%-40% reduction in cytosolic ROS levels. However, loss-of-function of ATG7 in cardiomyocytes or mouse myocardium abolished the protective effects of SAHA on ROS levels, mitochondrial membrane potential, mtDNA levels, and mitochondrial mass. Lastly, PGC-1α gene expression was induced by SAHA in NRVMs and mouse heart subjected to I/R, and loss of PGC-1α abrogated SAHA's mitochondrial protective effects in cardiomyocytes. CONCLUSIONS: SAHA prevents I/R induced-mitochondrial dysfunction and loss, and reduces myocardial ROS production when given before or after the ischemia. The protective effects of SAHA on mitochondria are dependent on autophagy and PGC-1α-mediated mitochondrial biogenesis.


Assuntos
Morte Celular Autofágica , Cardiotônicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/metabolismo , Vorinostat/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
12.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640238

RESUMO

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives 6-14. The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were 6 and 14, which exhibited excellent potencies comparable to quinazolinone derivatives 5 and 9, respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety (11a-d). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives (11a-d) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in p-position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.


Assuntos
Antineoplásicos/síntese química , Antioxidantes/síntese química , Quinazolinonas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Células MCF-7 , Estrutura Molecular , Quinazolinonas/química , Quinazolinonas/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Tionas/química
13.
J Surg Oncol ; 118(8): 1285-1291, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30399200

RESUMO

BACKGROUND AND OBJECTIVES: Prolonged air leaks (PAL) are the most frequent complication after lobectomy for non-small cell lung cancer, even in case of minimally invasive approaches. We developed a novel score to identify high-risk patients for PAL during minimally invasive lobectomy. METHODS: A dedicated database was created. We investigated preoperative candidate features and specific intraoperative variables. Univariate and subsequent logistic regression analysis with bootstrap resampling have been used. Model performance has been assessed by reckoning the area under the receiver operating characteristics curve and the Hosmer-Lemeshow goodness of fit. RESULTS: PAL (>5 days) occurred in 72 (15.69%) patients. Five variables emerged from the model. Each one was assigned a score to provide a cumulative scoring system: forced expiratory volume in 1 second below 86% (P = 0.004, 1.5 points), body mass index <24 ( P = 0.002, 1 point), active smoking ( P = 0.001, 1.5 points), incomplete fissures ( P = 0.004, 1.5 points), and adhesions ( P = 0.0001, 1 point). The new score provided a stratification into four risk classes. CONCLUSIONS: The risk score incorporates either general or more specific variables, providing a risk stratification that could be readily applied intra- and postoperatively. Henceforth, specific technical and management measures could be properly allocated to curb PAL.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Doenças Pleurais/prevenção & controle , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Modelos Estatísticos , Doenças Pleurais/etiologia , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco
14.
J Clin Ultrasound ; 46(9): 585-587, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30229915

RESUMO

Most guidelines on ultrasound examinations during pregnancy do not recommend routine early pregnancy scan in uncomplicated and asymptomatic pregnancies (ie, before 10 weeks based on last menstrual period). There is, however, a growing patient's expectation to have an early scan to confirm dating and verify the pregnancy is intrauterine and viable. We present three well-documented cases of patients who had an early (7-8 weeks) dating transvaginal scan revealing pleural effusion in the embryo. In all cases cytogenetic analysis confirmed monosomy for the X chromosome, consistent with a clinical diagnosis of Turner syndrome.


Assuntos
Imageamento Tridimensional/métodos , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/embriologia , Primeiro Trimestre da Gravidez , Síndrome de Turner/complicações , Ultrassonografia Pré-Natal/métodos , Adulto , Diagnóstico Precoce , Feminino , Humanos , Derrame Pleural/complicações , Gravidez , Síndrome de Turner/diagnóstico por imagem , Síndrome de Turner/embriologia , Adulto Jovem
15.
Clin Immunol ; 179: 40-46, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28286113

RESUMO

Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4+ FoxP3+ regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression. Compared to healthy volunteers the frequency of CD45RA+FoxP3low Treg was reduced in MG patients in general (p=0.037) and in particular in patients without immunosuppression (p=0.036). In our study, thymectomy and immunosuppressive treatment were associated with changes in Treg subpopulations. The reduced frequency of CD45RA+FoxP3low Treg we observed in MG patients might play a role in MG pathogenesis.


Assuntos
Miastenia Gravis/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/cirurgia , Subpopulações de Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Timectomia , Timoma/tratamento farmacológico , Timoma/imunologia , Timoma/cirurgia , Timo/patologia , Hiperplasia do Timo/tratamento farmacológico , Hiperplasia do Timo/imunologia , Hiperplasia do Timo/cirurgia , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/imunologia , Neoplasias do Timo/cirurgia
16.
J Surg Res ; 220: 147-163, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29180177

RESUMO

BACKGROUND: Although cutting electrocautery can be superior to the scalpel in reducing blood loss and incisional time, several reports associated electrocautery with higher rates of wound infection, impaired healing, and worse cosmesis. We performed this systematic review and meta-analysis to compare cutting electrocautery versus scalpel for surgical incisions. MATERIALS AND METHODS: We conducted a computerized literature search of five electronic databases and included all published original studies comparing cutting electrocautery and scalpel surgical incisions. Relevant data were extracted from eligible studies and pooled as odds ratios (ORs) or standardized mean difference (SMD) values in a meta-analysis model, using RevMan and Comprehensive Meta-analysis software. RESULTS: Forty-one studies (36 randomized trials, four observational, and one quasirandom study) were included in the pooled analysis (6422 participants). Compared with the scalpel incision, cutting electrocautery resulted in significantly less blood loss (SMD = -1.16, 95% CI [-1.60 to -0.72]), shorter incisional (SMD = -0.63, 95% CI [-0.96 to -0.29]) and operative times (SMD = -0.59, 95% CI [-1.12 to -0.05]), and lower pain scores (SMD = -0.91, 95% CI [-1.27 to -0.55]) with no significant differences in terms of wound infection rates (OR = 0.92, 95% CI [0.74-1.15]) or overall subjective scar score (SMD = -0.49, 95% CI [-1.72 to 0.75]). CONCLUSIONS: Surgical incision using electrocautery can be quicker with less blood loss and postoperative pain scores than the scalpel incision. No statistically significant difference was found between both techniques in terms of postoperative wound complications, hospital stay duration, and wound cosmetic characteristics. Therefore, we recommend routine use of cutting electrocautery for surgical incisions.


Assuntos
Cicatriz/epidemiologia , Eletrocoagulação/efeitos adversos , Instrumentos Cirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Ferida Cirúrgica/complicações , Cicatrização , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Cicatriz/etiologia , Humanos , Tempo de Internação , Duração da Cirurgia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Resultado do Tratamento
17.
Neurol Sci ; 38(11): 1963-1968, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28808795

RESUMO

Cerebral venous thrombosis (CVT) usually accounts for < 1% of all strokes. Global disparity and diversity in their demographics, etiology, clinical features, radiological presentation, and mortality have not been previously explored. A systematic search was performed for publications in PubMed using key words "cerebral venous thrombosis," "Cerebral vein thrombosis," and "Cortical vein Thrombosis." A total of 600 relevant studies were abstracted with strict selection criteria, and a total of 7048 patient's data were used for the final analysis. The frequency and relative frequency statistics were used to describe the data. Cases reported were Europe-3152, Asia-2722, North America-852, Africa-122, Australia-121, and South America-79. Overall male to female ratio was 1:2.2; among clinical characteristics, headache was the most common symptom and hematological factors were the most common etiology. Location of the thrombosis was described mostly in the transverse sinus. Intercontinental differences in relation to demographics, etiology, clinical features, radiological presentation, and mortality were identified. CVT can have significant disparity in their demographics, etiology, clinical features, radiological presentation, and mortality when compared from one continent to other. It is important for the worldwide physicians to recognize these differences and to follow the most recent guidelines, diagnostic methods, and treatment to insure the best outcome and prognosis.


Assuntos
Veias Cerebrais , Trombose Intracraniana/epidemiologia , Trombose Venosa/epidemiologia , Humanos
18.
Trop Anim Health Prod ; 49(2): 295-301, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27913973

RESUMO

Rabbit hemorrhagic disease is an acute fatal highly contagious viral infectious disease that causes high losses among rabbitries. The disease was first reported in China in 1984 and later on in Saudi Arabia in 1996. The aim of this study was to investigate the emergence and pathogenicity of new rabbit hemorrhagic disease virus (RHDV) strains in Saudi Arabia. The pathogenicity was confirmed by inoculation in susceptible rabbits. Three RHDV strains were detected by reverse transcriptase polymerase chain reaction (RT-PCR) using primers targeting VP60 capsid protein gene in infected rabbitries during 2012 and 2013. These strains clustered into two genetically distinct genogroups related to year of isolation (G2 and G3). All new Saudi Arabia viruses clustered with the European strains, while the old strains clustered with strains from China and America. Based on amino acids and nucleotide sequences, the Saudi Arabia strains (RHD/1/SA/2012, RHD/2/SA/2012, and RHD/3/SA /2013) had high identity with Mexico89, Ca11-ITA, and 00-13,FRA virus; on the other hand, there was a relatively high identity with Bahrain strain. The evolutionary relationship of Saudi RHDVs strains revealed significant nucleotides and amino acid substitutions in hypervariable region E, suggesting the emergence of new RHDVs circulating in Saudi Arabia rabbitries. These antigenic changes represented by the antigenic index might be a potential cause of vaccination failure and raises the need to review the vaccination strategies against RHD.


Assuntos
Infecções por Caliciviridae/veterinária , Vírus da Doença Hemorrágica de Coelhos/genética , Vírus da Doença Hemorrágica de Coelhos/patogenicidade , Proteínas Estruturais Virais/genética , Animais , Infecções por Caliciviridae/virologia , Evolução Molecular , Genótipo , Vírus da Doença Hemorrágica de Coelhos/classificação , Filogenia , Coelhos , Arábia Saudita , Análise de Sequência de RNA/veterinária , Virulência
19.
Am J Obstet Gynecol ; 214(5): 659.e1-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26608832

RESUMO

BACKGROUND: Clinical management and outcome of multiple gestation can be affected by chorionicity. In triplet pregnancies, fetal death has been associated with dichorionic (DC) and monochorionic placentation. Studies evaluating triplet pregnancy outcomes in relation to chorionicity have been few and may not reflect contemporary antenatal and neonatal care. OBJECTIVE: The objective of this study was to compare obstetric and perinatal outcomes in DC and trichorionic (TC) triplet pregnancies. STUDY DESIGN: We performed a retrospective cohort study of triplet pregnancies that delivered at ≥20 weeks' gestation at 2 Chicago area hospitals from January 1999 through December 2010. Chorionicity was determined by pathology specimen. Maternal and infant charts were reviewed for obstetric and perinatal outcomes. RESULTS: The study population included 159 pregnancies (477 neonates) of which 108 were TC (67.9%) and 51 were DC (32.1%). Over 94% of mothers in this study had all 3 infants survive to discharge regardless of chorionicity. No difference was found in perinatal mortality rate between DC and TC triplets (3.3% vs 4.6%; P = .3). DC triplets were significantly more likely to be very low birthweight (41.8% vs 22.2%; odds ratio, 2.2; 95% confidence interval, 1.2-4.2; P = .02) and to deliver at <30 weeks (25.5% vs 8.3%; odds ratio, 6.1; 95% confidence interval, 1.9-19.4; P = .002) compared to TC triplets. Criteria for twin-twin transfusion syndrome (TTTS) were present in 3 DC triplet pregnancies (5.9%). Neonates in pregnancies complicated by TTTS were less likely to survive 28 days as compared to neonates from DC pregnancies that were not affected by TTTS (P = .02) or TC neonates (P = .02) Neonatal survival was similar in DC pregnancies not affected by TTTS and TC pregnancies (98.6% and 96.6%; P = .7). CONCLUSION: Although perinatal mortality did not correlate with chorionicity, DC pregnancies were more likely to deliver <30 weeks' gestational age and have very low birthweight neonates. Neonatal mortality appears to be mediated by the presence or absence of TTTS as 28-day survival was worse in DC pregnancies complicated by TTTS, but similar between DC pregnancies not affected by TTTS and TC pregnancies.


Assuntos
Córion , Gravidez de Trigêmeos , Adulto , Chicago/epidemiologia , Estudos de Coortes , Feminino , Transfusão Feto-Fetal/mortalidade , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Pessoa de Meia-Idade , Gravidez , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Adulto Jovem
20.
Thorac Cardiovasc Surg ; 63(3): 194-200, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25806663

RESUMO

BACKGROUND: Thymectomy is an essential component in the treatment of myasthenia gravis (MG) and the best treatment for localized thymoma. Minimally invasive thymectomy has advanced to include robotic-assisted techniques. The acceptance of this approach is growing rapidly, while the debate on the adequate technique for thymectomy remains open. METHODS: We describe the technique of robotic-assisted thymectomy and its modifications. The worldwide registries and the literature are reviewed. The experience from the largest single-center database is analyzed. RESULTS: The unilateral three-trocar approach for robotic thymectomy from either left or right side has been standardized. More than 100 centers worldwide perform robotic thymectomy. The annual number of this procedure increased steadily and reached 1,000 in 2012, while the largest single-center experiences comprise almost 500 cases. The end points improvement of MG and recurrence of thymoma are comparable to open procedures. There are special advantages of robotic assistance for complete mediastinal dissection. The perioperative complication rate is below 2%. CONCLUSION: Robotic thymectomy combines minimal incisional discomfort with extensive mediastinal dissection. As its use expands, robotic thymectomy may become the standard for all indications of thymectomy.


Assuntos
Robótica/métodos , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Coristoma/cirurgia , História do Século XX , Humanos , Miastenia Gravis/cirurgia , Robótica/história , Timectomia/história , Resultado do Tratamento
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