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1.
Colloids Surf B Biointerfaces ; 188: 110824, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023511

RESUMO

Despite the clinical approval of few nanomedicines for cancer therapy, some drawbacks still impede their improved efficiency including low drug loading, off-target toxicity and development of multi-drug resistance. Herein, lactoferrin (Lf)-coupled mesoporous silica nanoparticles (MSNPs) were developed for combined delivery of the cytotoxic drug pemetrexed (PMT) and the phytomedicine ellagic acid (EA) for synergistic breast cancer therapy. While the hydrophobic EA was physically encapsulated within the pores of MSNPs via the adsorptive properties of MSNPs and the electrostatic interactions between the negatively charged EA and positively charged amino modified MSNs, the highly water soluble PMT was chemically anchored to the Lf shell through chemical conjugation to the surface of lactoferrin coated MSNPs by carbodiimide reaction to avoid pre-mature drug release and systemic toxicity. The dual drug-loaded Lf-MSNPs (284 nm) demonstrated a sequential faster release of EA followed by a sustained release of PMT. The dual drug-loaded Lf-MSNPs exhibited highest cytotoxicity against MCF-7 (Michigan Cancer Foundation-7) breast cancer cells as revealed by the lowest combination index (CI = 0.885) compared to free drugs. The combination index value (< 1) revealed synergy between both loaded drugs. Furthermore, high cellular uptake of the nanocarriers into MCF-7 breast cancer cells was observed via Lf-receptor mediated endocytosis. Altogether, the dual drug-loaded Lf-targeted MSNPs showed to be a promising carrier for breast cancer therapy through triggering different signaling pathways, and hence overcoming the multi-drug resistance and minimizing the systemic toxicity.

2.
Bioorg Chem ; 96: 103616, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32032847

RESUMO

Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network and significance of their inhibition for treatment of various diseases like arthritis, cancer, atherosclerosis and Alzheimer. Within this approach, dual MMP-10/13 inhibition was disclosed as new approach for targeted polypharmacology. While several efficient MMP-13 inhibitors are known, very few potent and selective MMP-10 inhibitors were reported. This study describes the design, synthesis and optimization of novel MMP-10/13 inhibitors with enhanced MMP-10 potency and selectivity towards polypharmacology. Starting with a lead fused pyrimidine-based MMP-13 inhibitor with weak MMP-10 inhibition, a structure-based design of pyrimidine and fused pyrimidine scaffolds was rationalized to enhance activity against MMP-10 in parallel with MMP-13. Firstly, a series of 6-methyl pyrimidin-4-one hydrazones 6-10 was synthesized via conventional and ultrasonic-assisted methods, then evaluated for MMP-10/13 inhibition. The most active derivative 9 exhibited acceptable dual potency with 7-fold selectivity for MMP-10 (IC50 = 53 nM) over MMP-13. Such hydrazones were then cyclized to the corresponding isomeric 1,2,4-triazolo[4,3-a]pyrimidines 12-19. Their MMP-10/13 inhibition assay revealed, in most cases, superior dual activities with general MMP-10 selectivity compared to the corresponding precursors 6-10. In addition, a clear structure activity relationship trend was deduced within the identified regioisomers, where the 5-oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives 15 and 16 were far more active against MMP-10/13 than their regioisomers 12 and 13. Remarkably, the p-bromophenyl derivative 16 exhibited the highest MMP-10 inhibition (IC50 = 24 nM), whereas the p-methoxy derivative 18 was the most potent MMP-13 inhibitor (IC50 = 294 nM). Moreover, 16 exhibited 19-fold selectivity for MMP-10 over MMP-13, 10-fold over MMP-9, and 29-fold over MMP-7. Docking studies were performed to provide reasonable explanation for structure-activity relationships and isoform selectivity. 16 and 18 were then evaluated for their anticancer activities against three human cancers to assess their therapeutic potential at cellular level via MTT assay. Both compounds exhibited superior anticancer activities compared to quercetin. Their in silico ligand efficiency metrics, physicochemical properties and ADME parameters were drug-like. Guided by such findings that point to 16 as the most promising compound in this study, further structure optimization was carried out via photoirradiation-mediated Dimroth rearrangement of the inactive triazolopyrimidine 13 to its potent regioisomer 16.

4.
Eur J Med Chem ; 186: 111875, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740054

RESUMO

Matrix metalloproteinases (MMPs) are major modulators of the tumor microenvironment. They participate in extracellular matrix turnover, tumor growth, angiogenesis and metastasis. Accordingly, MMPs inhibition seems to be ideal solution to control cancer. Many MMPs inhibitors have been introduced ranging from hydroxamate-based peptidomimetics to the next generation non-hydroxamate inhibitors. Among MMPs, MMP-9 is attractive druggable anticancer target. Studies showed that inhibiting AKT, the central signaling node of MMP-9 upregulation, provides additional MMP-9 blockade. Furthermore, caspase-dependent AKT cleavage leads to cell death. Herein, Ugi MCR was utilized as a rapid combinatorial approach to generate various decorated bis-amide scaffolds as dual MMP-9/AKT inhibitors endowed with caspase 3/7 activation potential. The target adducts were designed to mimic the thematic structural features of non-hydroxamate MMP inhibitors. p-Nitrophenyl isonitrile 1 was utilized as structure entry to Ugi products with some structural similarities to amide-based caspase 3/7 activators. Besides, various acids, amines and aldehydes were employed as Ugi educts to enrich the SAR data. All adducts were screened for cytotoxicity against normal fibroblasts and three cancer cell lines; MCF-7, NFS-60 and HepG-2 utilizing MTT assay. 8, 11 and 28 were more active and safer than doxorubicin with single-digit nM IC50 and promising selectivity. Mechanistically, they exhibited dual MMP-9/AKT inhibition at single-digit nM IC50 with excellent selectivity over MMP-1,-2 and -13, and induced >51% caspase 3/7 activation. Consequently, they induced >49% apoptosis as detected by flow cytometric analysis, and inhibited cell migration (metastasis) up to 97% in cancer cells. Docking simulations were nearly consistent with enzymatic evaluation, also declared possible binding modes and essential structure features of active compounds. In silico physicochemical properties, ligand efficiency and drug-likeness metrics were reasonable for all adducts. Interestingly, 8 and 28 can be considered as drug-like candidates.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Amidas/síntese química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inibidores de Metaloproteinases de Matriz/síntese química , Inibidores de Metaloproteinases de Matriz/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
5.
Bioorg Chem ; 92: 103189, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473473

RESUMO

Angiogenesis is a hallmark in cancer. Most antiangiogenic agents block the action of vascular endothelial growth factor (VEGF). In clinic, patients develop hypoxia-mediated resistance consistent with vascular responses to these agents. Recent studies underlying such resistance revealed hypoxia-inducible PIM-1 kinase upregulation which promotes cancer progression. PIM-1 kinase expression is thus viewed as a new resistance mechanism to antiangiogenic agents. Hence, combining PIM kinase inhibitors with anti-VEGF therapies provides synergistic antitumor response. Inspired by these facts, the current study aims at designing novel dual VEGFR-2/PIM-1 kinase inhibitors via molecular hybridization and repositioning of their pharmacophoric features. Moreover, enhancing the cytotoxic potential of the designed compounds was considered via incorporating moieties mimicking caspase 3/7 activators. Accordingly, series of novel pyridine and thieno[2,3-b]pyridine derivatives were synthesized and screened via MTT assay for cytotoxic activities against normal fibroblasts and four cancer cell lines (HepG-2, Caco-2, MCF-7 and PC-3). Compounds 3a, 9e, 10b and 10c exhibited anticancer activities at nanomolar IC50 with promising safety, activated caspase 3/7 and induced apoptosis as well as DNA fragmentation more than doxorubicin in the four cancer cell lines. Furthermore, they exerted promising dual VEGFR-2/PIM-1 kinase inhibition and significantly exhibited higher therapeutic potential to alter the expression levels of VEGF, p53 and cyclin D than doxorubicin. Interestingly, the most active anticancer compound 10b conferred the highest dual VEGFR-2/PIM-1 kinase inhibition. Finally, their in silico ligand efficiency metrics were acceptable.

6.
Bioorg Chem ; 88: 102915, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005784

RESUMO

Drugs targeting different calcium channel subtypes have strong therapeutic potential for future drug development for cardiovascular disorders, neuropsychiatric diseases and cancer. This study aims to design and synthesize a new series of C2 substituted dihydropyrimidines to mimic the structure features of third generation long acting dihydropyridine calcium channel blockers and dihydropyrimidines analogues. The target compounds have been evaluated as blockers for CaV1.2 and CaV3.2 utilizing the whole-cell patch clamp technique. Among the tested compounds, compound 7a showed moderate calcium channel blockade activity against CaV3.2. Moreover, the predicted physicochemical properties and pharmacokinetic profiles of the target compounds recommend that they can be considered as drug-like candidates. The results highlight some significant information for the future design of lead compounds as calcium channel blockers.

7.
J Invasive Cardiol ; 31(6): 187-194, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30865914

RESUMO

OBJECTIVES: We evaluated the efficacy of low-dose (LD) radiation (≤7.5 frames/second [f/s]) compared with standard-dose (SD) radiation (≥10 f/s) in cardiac catheterization (CC) and percutaneous coronary intervention (PCI). Patients undergoing CC with LD vs SD radiation have not been previously studied. METHODS: We performed an observational study of 452 consecutive patients (61 ± 12 years) who had coronary angiography or PCI from September 2016 to September 2017. Patients were divided into an LD radiation group (n = 136) consisting of 0.5 f/s and 1 f/s (n = 73), 4 f/s (n = 40), or 7.5 f/s fluoroscopy (n = 23) with 7.5 f/s cine angiography vs an SD group (n = 316) consisting of 10 f/s (n = 250), 15 f/s (n = 64), or 30 f/s fluoroscopy (n = 2) and 10-30 f/s cine angiography. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. RESULTS: Compared with SD radiation, LD radiation was associated with a significant reduction in air kerma (100.70 mGy [IQR, 46.42-233.35 mGy] vs 660.96 mGy [IQR, 362.78-1373.65 mGy]; P<.001), DAP (723.60 µGy•m² [IQR, 313.09-2328.22 µGy•m²] vs 5203.40 µGy•m² [IQR, 2743.55-10064.71 µGy•m²]; P<.001), and contrast use (100 mL [IQR, 60-150 mL] vs 115 mL [IQR, 80-180 mL]; P<.03). No difference in fluoroscopy time was noted (13.33 min [IQR, 6.93-25.55 min] vs 12.75 min [IQR, 7.75-22.55 min]; P=.95). CONCLUSIONS: LD radiation in CC was efficacious, with significant radiation reduction and without an increase in fluoroscopy time or contrast utilization. All patients underwent successful LD radiation catheterization without conversion to SD.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Cateterismo Cardíaco/métodos , Angiografia Coronária/métodos , Fluoroscopia/métodos , Intervenção Coronária Percutânea/métodos , Cirurgia Assistida por Computador/métodos , Síndrome Coronariana Aguda/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial , Doses de Radiação , Estudos Retrospectivos , Fatores de Risco
8.
Eur J Med Chem ; 168: 340-356, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30826510

RESUMO

Evasion of apoptosis is a hallmark of cancer. Caspases; the key executors of apoptotic cascade are attractive targets for selective induction of apoptosis in cancer cells. Within this approach, various caspase activators were introduced as lead anticancer agents. In the current study, a new series of multifunctional Passerini products was synthesized and evaluated as potent caspase-dependent apoptotic inducers. The synthetic strategy adopted this isocyanide-based multicomponent reaction to possibly mimic the pharmacophoric features of various lead apoptotic inducers, where a series of α-acyloxy carboxamides was prepared from p-nitrophenyl isonitrile, cyclohexanone and various carboxylic acids. Accordingly, the main amide-based scaffold was decorated by substituents with varying nature and size to gain more information about structure-activity relationship. All the synthesized compounds were screened for cytotoxicity against normal human fibroblasts and their potential anticancer activities against three human cancer cell lines; MCF-7 (breast), NFS-60 (myeloid leukemia), and HepG-2 (liver) utilizing MTT assay. Among the most active compounds, 13, 21 and 22 were more potent and safer than doxorubicin with nanomolar IC50 values and promising selectivity indices. Mechanistically, 13, 21 and 22 induced apoptosis by significant caspase activation in all the screened cancer cell lines utilizing flow cytometric analysis and caspase 3/7 activation assay. Again, 13 and 21 recorded higher activation percentages than doxorubicin, while 22 showed comparable results. Apoptosis-inducing factor1 (AIF1) quantification assay declared that 13, 21 and 22 didn't mediate apoptosis through AIF1-dependent pathway (i.e. only by caspase activation). Physicochemical properties, pharmacokinetic profiles, ligand efficiency metrics and drug-likeness data of all the synthesized compounds were computationally predicted and showed that 13, 21 and 22 could be considered as drug-like candidates. Finally, selected compounds were preliminarily screened for possible antimicrobial activities searching for dual anticancer/antimicrobial agents as an advantageous approach for cancer therapy.


Assuntos
Amidas/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Caspase 3/metabolismo , Caspase 7/metabolismo , Desenho de Drogas , Amidas/química , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Candida albicans/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
9.
Bioorg Chem ; 86: 557-568, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782574

RESUMO

In search of potent acetyl cholinesterase inhibitors with low hepatotoxicity for the treatment of Alzheimer's disease, introduction of a chloro substitution to tacrine and some of its analogs has proven to be beneficial in maintaining or potentiating the cholinesterase inhibitory activity. Furthermore, it was found to be able to reduce the hepatotoxicity of the synthesized compounds, which is the main target of the study. Accordingly, a series of new 4-(chlorophenyl)tetrahydroquinoline derivatives, was synthesized and characterized. The synthesized compounds were evaluated for their in vitro and in vivo anti-cholinesterase activity using tacrine as a reference standard. Furthermore, they were investigated for their hepatotoxicity compared to tacrine. The obtained biological results revealed that all synthesized compounds displayed equivalent or significantly higher anti-cholinesterase activity and lower hepatotoxicity in comparison to tacrine. In addition, in silico drug-likeness of the synthesized compounds were predicted and their practical logP were assessed indicating that all synthesized compounds can be considered as promising hits/leads. Furthermore, docking study of the compound showing the highest in vitro anticholinesterase activity was performed and its binding mode was compared to that of tacrine.

10.
Urology ; 126: 217-221, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30605695

RESUMO

OBJECTIVE: To compare outcome of muscle and nerve-sparing bulbar urethroplasty with standard bulbar urethroplasty as regard ejaculatory dysfunction and postvoid dribbling. METHODS: This prospective randomized study included 50 patients with bulbar urethral stricture underwent urethroplasty over a period of 5 year. All patients were operated by ventral onlay buccal mucosal graft urethroplasty and randomly divided into 2 groups. Group I (n = 25) was operated by standard bulbar urethroplasty. Group II (n = 25) was operated by bulbar urethroplasty with preservation of bulbospongiosus muscle and nerve. Postoperative follow-up was performed at 1-, 6-, and 12-month and annually thereafter. Urethrography was done at 1-month, while uroflowmetry was performed at 6- and 12-month. Urethrography was indicated if Qmax <14 mL/sec. Success was defined as normal voiding without any auxiliary procedures. RESULTS: Success rate was 88% and 92% in Group I and II, respectively. Urethral sacculation was not detected in any patient in either group. One patient from Group I was complicated by urinary extravasation after catheter removal and required re-catheterization for another 1week. One patient in each group was complicated by postoperative wound infection managed by antibiotics. Postvoid dribbling was the complaint of 9 patients in Group I and 1 patient in Group II, while semen sequestration was present in 10 and 2 patients in Group I and Group II, respectively. Significant differences were observed between the 2 groups as regard postvoid dribbling and ejaculatory dysfunction. CONCLUSION: Bulbar urethroplasty with bulbospongiosus muscle and nerve-sparing seems to be a safe and effective alternative for standard bulbar urethroplasty.


Assuntos
Uretra/cirurgia , Estreitamento Uretral/cirurgia , Adulto , Humanos , Masculino , Mucosa Bucal/transplante , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
11.
Bioorg Chem ; 83: 354-366, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30408648

RESUMO

New dihydropyrimidines bearing various lipophilic pharmacophores and functionalities at position 3 were designed and synthesized. The basic framework of the new compounds was designed to maintain the main structural requirements for calcium channel blocking activity of the known dihydropyridines and dihydropyrimidines calcium channel blockers. The newly synthesized compounds were evaluated as antagonists for CaV1.2 and CaV3.2 using the whole-cell patch clamp technique. Seven compounds (4b, 4c, 6c, 9, 13c, 13e and 17b) showed promising dual calcium channel blocking activity and three compounds (13b, 14b and 17a) were selective against Cav3.2. Their drug-likeness has been assessed using Molinspiration and Molsoft softwares. Their physicochemical properties and pharmacokinetic profiles recommend that they can be considered as drug-like candidates.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Pirimidinas/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/síntese química , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Linhagem Celular , Desenho de Drogas , Humanos , Estrutura Molecular , Técnicas de Patch-Clamp , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/farmacocinética , Ratos , Solubilidade , Relação Estrutura-Atividade
12.
Curr Vasc Pharmacol ; 17(3): 278-290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29345588

RESUMO

BACKGROUND: Chronic total occlusion (CTO) of a coronary artery is defined as an occluded segment with no antegrade flow and a known or estimated duration of at least 12 weeks. OBJECTIVE: We considered the current literature describing the indications and clinical outcomes for denovo CTO- percutaneous coronary intervention (PCI), and discuss the role of CTO-PCI and future directions for this procedure. METHODS: Databases (PubMed, the Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL were searched and relevant studies of CTO-PCI were selected for review. RESULTS: The prevalence of coronary artery CTO's has been reported to be ~ 20% among patients undergoing diagnostic coronary angiography for suspected coronary artery disease. Revascularization of any CTO can be technically challenging and a time-consuming procedure with relatively low success rates and may be associated with a higher incidence of complications, particularly at non-specialized centers. However, with an increase in experience and technological advances, several centers are now reporting success rates above 80% for these lesions. There is marked variability among studies in reporting outcomes for CTO-PCI with some reporting potential mortality benefit, better quality of life and improved cardiac function parameters. Anecdotally, properly selected patients who undergo a successful CTO-PCI most often have profound relief of ischemic symptoms. Intuitively, it makes sense to revascularize an occluded coronary artery with the goal of improving cardiovascular function and patient quality of life. CONCLUSION: CTO-PCI is a rapidly expanding specialized procedure in interventional cardiology and is reasonable or indicated if the occluded vessel is responsible for symptoms or in selected patients with silent ischemia in whom there is a large amount of myocardium at risk and PCI is likely to be successful.

13.
Interv Neurol ; 7(6): 327-333, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30410509

RESUMO

Background: Treatment of large vessel occlusion acute ischemic stroke with mechanical thrombectomy has become the standard of care after recent clinical trials. However, the degree of recanalization with stent retrievers remains very important in overall outcomes. We sought to review the utility of a new balloon guide catheter (BGC) in improving the degree of recanalization in conjunction with mechanical thrombectomy. Methods: The medical records of a prospectively collected endovascular ischemic stroke database were reviewed. All consecutive strokes when a FlowGate BGC was used with a thrombectomy stent retriever were identified. Use of a FlowGate BGC, number of passes, final Thrombolysis in Cerebral Infarction (TICI) score, trackability, and use of adjunct devices were all collected and analyzed. Results: Use of a FlowGate BGC resulted in 64% (33/52) first-pass effect (FPE) of TICI 2b/3, and specifically 46% (24/52) TICI 3 FPE (true FPE). A total of 52/62 (84%) of thrombectomy cases were treated with BGCs. In the remaining 10, the BGC was not inflated or used due to the clot not being visualized or the lesions being distal and BGC use thus not deemed appropriate. Adjunct use of an aspiration catheter was seen in 12% (6/52) of cases. The overall success with FlowGate BGCs with one or more passes of TICI 2b/3 was 94% (49/52). Trackability was achieved in 92% (57/62) of cases. Conclusions: Use of the FlowGate BGC as an adjunct to mechanical thrombectomy was associated with good FPE and an overall recanalization of TICI 2b/3 of 94%.

14.
Am J Med Sci ; 355(6): 573-580, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29891041

RESUMO

Joint hypermobility is a common, primarily benign finding in the general population. However, in a subset of individuals joint hypermobility causes a range of clinical problems mainly affecting the musculoskeletal system and, to a lesser extent, extra-articular disorders. Joint hypermobility often appears as a familial trait and is shared by several inherited connective tissue disorders, including the hypermobility subtype of Ehlers-Danlos syndrome (hEDS) and benign joint hypermobility syndrome (BJHS/JHS). Although joint hypermobility has primarily been thought of as a rheumatological disorder, increasing evidence shows significant associations between both hEDS and BJHS with specific extra-articular disorders. To date, the strongest associations of these 2 conditions are with anxiety disorders, orthostatic tachycardia, various functional gastrointestinal (GI) disorders and pelvic and bladder dysfunction. This review article focuses on GI disorders associated with both hEDS and BJHS. The aim of this review is to evaluate existing research and literature regarding associations between JHS (hEDS/BJHS) and GI disorders. Our goal is to raise awareness of BJHS/JHS and hEDS as an explanation for chronic unexplained symptoms and functional GI disorders as well as to review the current standard tests available for proper evaluation of GI symptoms in these patients.


Assuntos
Gastroenteropatias/complicações , Instabilidade Articular/complicações , Instabilidade Articular/genética , Síndrome da Taquicardia Postural Ortostática/complicações , Adolescente , Adulto , Idoso , Feminino , Gastroparesia/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Instabilidade Articular/congênito , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Retais/complicações , Projetos de Pesquisa , Estudos Retrospectivos , Adulto Jovem
15.
Proc (Bayl Univ Med Cent) ; 31(3): 334-336, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29904303

RESUMO

The abuse of anabolic androgenic steroids (AAS) has remained on the rise despite their well-known deleterious effects. We describe a case of AAS-induced multisystem failure following an extensive history of abuse in a 41-year-old bodybuilder. Furthermore, we review pertinent literature and discuss the different pathophysiologic mechanisms through which AAS affect the heart and other organs. This case points to the possibility of multiorgan involvement and severe cardiac effects of AAS abuse in young individuals who may not have any past medical history.

16.
Proc (Bayl Univ Med Cent) ; 31(1): 20-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29686546

RESUMO

There is a strong relation between metabolic syndrome (MetS) and left ventricular (LV) mass in Hispanic patients. This population also tends to have a higher incidence of kidney disease, with progression to dialysis. We analyzed the change in LV mass in 982 Hispanic patients with MetS and used these data to anticipate the progression of renal dysfunction. Glomerular filtration rate (GFR) was calculated using the formula described by the Chronic Kidney Disease Epidemiology Collaboration. Echocardiographic data were collected using 2-dimensionally guided M-mode echocardiography measures. The data collected were then analyzed using linear regression analyses. Results showed a lower average GFR in individuals classified as having a severe change in LV mass in comparison to those with milder change in LV mass (P < 0.0001). This relation was also demonstrated when those with severe change in LV mass were compared with the control group (P < 0.0001). In those ≥54 years old, the presence of MetS and LV mass were negatively correlated with GFR (regression coefficient [RC] = 14.76, P < 0.063; RC = 0.11, P < 0.0001 respectively). In patients <54 years old, no statistically significant association between the presence of MetS and GFR was seen. However, LV mass was once again negatively correlated with GFR (RC = 0.15, P < 0.0001). In conclusion, results demonstrated the association between the MetS, change in LV mass, and chronic kidney disease progression.

17.
Proc (Bayl Univ Med Cent) ; 31(1): 67-69, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29686558

RESUMO

Patent foramen ovale (PFO) occurs in 25% of people. The decision on whether to close the PFO found after myocardial infarction and specifically right ventricular infarction is debated, with no solid guidelines addressing this subject. Here we present the case of a 59-year-old man who presented with a myocardial infarction and was found to have PFO. He was treated with revascularization of the culprit artery, followed by supportive care.

18.
Curr Cardiol Rep ; 20(3): 17, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29511900

RESUMO

PURPOSE OF THE REVIEW: Coronary artery disease is a major cause of mortality and morbidity in the world, and PCI and CABG account for over a million procedures performed annually in the USA. The goal of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is to achieve complete revascularization (CR) if at all possible. However, restenosis and stent thrombosis (ST) remain the Achilles heel of contemporary PCI with restenosis rates between 10 and 30% with bare metal stents to 5-15% after drug-eluting stents and ST rates of around 0.8 vs 1.2%, respectively. Routine angiography after revascularization seems theoretically attractive as this may allow intervention before clinical events occur. In this manuscript, we review the literature regarding routine angiography after PCI or CABG and its outcomes. RECENT FINDINGS: According to the 2016 update from the American Heart Association (AHA), 15.5 million people above the age of 20 have coronary heart disease (CHD) in the USA. The prevalence of CHD is now almost similar in both men and women, and one American suffers from a myocardial infarction (MI) every 42 s. Recent data from randomized clinical trials and observational studies does not support the use of routine coronary angiography after revascularization in asymptomatic patients. There are some studies which show that routine angiography may have a role in left main or complex coronary interventions; however, these findings are exploratory and were not seen in randomized trials. After reviewing the data on routine angiography after coronary revascularization, we came to the conclusion that current data does not support the use of routine angiography for asymptomatic patients. However, there is a lack of randomized controlled trial in this field with only one recent trial reporting negative outcomes.


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Humanos , Infarto do Miocárdio/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
J Neurosci Nurs ; 50(2): 68-73, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29521729

RESUMO

BACKGROUND: Nurses play an integral role in triaging stroke patients. The purpose of this quality improvement initiative was to determine the efficacy of using an emergent large vessel occlusion (ELVO) screening protocol in the emergency department by nursing staff to improve identification of eligible patients as compared with current practice, improving time to endovascular treatment. METHODS: Retrospective chart review was used to identify 76 patients admitted to a large urban stroke center. Of these, 36 presented during a 4-month period before the implementation of the Stroke Vision, Aphasia, Neglect (Stroke VAN) tool for assessing ELVO risk; 40 patients were admitted during the 4 months after implementation of Stroke VAN. RESULTS: The mean door-to-computed tomography angiography scan times were reduced from 119 to 49 minutes (P < .0001) for all patients and reduced from 77 to 27 minutes in a subset of VAN-positive patients. CONCLUSION: Implementation of the VAN screening tool to assess for ELVO was associated with decreased door-to-computed tomography angiography times and more rapid identification of endovascular eligible patients with ischemic stroke.


Assuntos
Arteriopatias Oclusivas/diagnóstico , Isquemia Encefálica/complicações , Avaliação em Enfermagem , Melhoria de Qualidade , Acidente Vascular Cerebral/complicações , Idoso , Angiografia por Tomografia Computadorizada/métodos , Serviço Hospitalar de Emergência , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem no Hospital , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
20.
Chem Cent J ; 12(1): 29, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29541952

RESUMO

BACKGROUND: Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN). RESULTS: The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. CONCLUSION: In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins.

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