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1.
Bioorg Chem ; 96: 103619, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32036161

RESUMO

A series of Schiff bases 3, 5, 7 and hydrazones 9 were achieved via reaction of 5-(morpholinosulfonyl)indol-2,3-dione (1) with appropriate amines and/or hydrazide derivatives. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents. According to MIC and MBC results from compounds 9a, 9c, 7a, 3b, 3c, and 5b were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria together with moderate antifungal activities. Also, a multi-drug resistance study (MDRS) was carried out to evaluate the activity of most potent compounds, and these compounds showed considerable results compared with Norfloxacin and Tetracycline which observed no results against strains used in this study. The inhibitory activity of most potent compounds (3b, 3c, 5b, 7a, 9a, and 9c) against DNA gyrase isolated from S. aureus was examined. The results indicated that all of these derivatives inhibiting DNA gyrase and therefore lead to separate bacterial DNA and inhibit cell division. Compounds 3b, 9c showed to be very potent inhibitors towards S. aureus DNA gyrase with IC50 values (18.75 ± 1.2 and 19.32 ± 0.99 µM) respectively, compared with Ciprofloxacin (26.43 ± 0.64 µM). Molecular docking studies indicated that the synthesized compounds observed good binding with the enzyme and showed lower binding energy of the most promising compounds than a standard drug used, and enabled a better understanding of their structural features.

2.
Eur J Med Chem ; 188: 111977, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31927313

RESUMO

a series of 2-oxospiro[indoline-3,4'-pyran]derivatives 4 and 7 were obtained in good yield under mild conditions from the one-pot reaction of indole-2,3-dione derivatives 1, appropriate methylene active nitriles 2 and ß-dicarbonyl compound 3 or 6. The newly synthesized compounds were characterized and evaluated for their in vitro antibacterial, antifungal as well as immunomodulatory activity. According to MIC values, the most potent compounds 4f, 4h, 7a, 7c, 7e, 7f, 7g, 8a, and 8c were evaluated for MBC and displayed high activity to killing pathogens with a good MBC value against norfloxacin as well as investigated against an extended panel of multidrug resistance bacteria (MDRB) and exhibited promising to moderate multidrug resistance activities, compounds 7f showed the much better than norfloxacin with higher potency results. Furthermore, the most potent compounds showed an increase in the intracellular killing activity of neutrophils which confirmed the immunostimulatory power. Eight of the nine active compounds exhibited inhibitory activities with IC50 ranged between (18.07 ± 0.18) to (27.03 ± 0.24) µM stronger than ciprofloxacin (26.43 ± 0.64 µM) for S. aureus DNA gyrase. Molecular docking was performed inside the active site of S. aureus DNA gyrase to predict the binding mode.

3.
Hum Fertil (Camb) ; : 1-6, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838927

RESUMO

This study aimed to demonstrate the effect of conventional freezing versus cryoprotectant-free vitrification on the recovery of testicular sperm motility. Testicular samples were obtained from 50 patients with azoospermia for testicular biopsy ± potential sperm storage. We retrieved 100 spermatozoa from each patient divided equally into two straws. They were frozen using conventional freezing as a control group and cryoprotectant-free vitrification in micro-capillary system using open-pulled straws. Seven days later, cryopreserved straws were thawed and assessed in duplicate. The mean sperm motility between the original spermatozoa sample and the post warming sample was reduced after conventional freezing compared to cryoprotectant-free vitrification (4.48 ± 2.09% versus 3.25 ± 1.92%, p < 0.001; 4.48 ± 2.09% vs 3.68 ± 1.93%, p < 0.001, respectively). There was a significant difference between the two methods regarding the mean sperm motility after warming (3.38 ± 1.86% versus 3.76 ± 1.88%, p = 0.015). The mean recovery percent of testicular sperm motility from the original sperm sample was lower (p = 0.02) after conventional freezing compared to cryoprotectant-free vitrification (78.4 ± 28.17% versus 85.37 ± 23.63%). Overall, the rate of post-thaw recovery of human testicular sperm motility improved using cryoprotectant-free vitrification compared to conventional freezing.

4.
Am J Cardiol ; 124(9): 1436-1441, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31481179

RESUMO

Reports on development of frequent ventricular premature complexes (fVPC), (non)sustained ventricular tachycardias ([n]sVT), or ventricular fibrillation (VF) and their interrelationship in patients with different inherited cardiac arrhythmia (ICA) have sofar not been reported. The aim of this study is therefore to examine incidences and recurrences rates of sVT and VF ("malignant ventricular tachyarrhythmias, VTA") in addition to the incidence of fVPC and nsVT ("ventricular dysrhythmias, VDR") in patients with various ICA during long-term follow up. Patients (N = 167, 88 male, age 45 ± 15 years) with ICA including definite/borderline arrhythmogenic right ventricular cardiomyopathy (ARVC, N = 47), Brugada syndrome (BrS, N = 71), catecholaminergic polymorphic ventricular tachycardia (CPVT, N = 7), long QT syndrome (LQTS, N = 41) or short QT syndrome (SQTS, N = 1) who had frequent 24-hour Holter monitoring during a follow-up period of 4.6 ± 4.4 years. During the initial screening visit, 15 patients had a history of malignant VTA. fVPC and nsVT was observed in respectively 19% (OHCA/VF/sVT: N = 9) and 13% (OHCA/VF/sVT: N = 4) of all patients. Compared with the ARVC group, patients with BrS and LQTS had less frequent fVPC and nsVT (fVPC: odds ratio [OR] 0.20, 95% confidence interval [CI] 0.08 to 0.49, p <0.000 and OR 0.09, 95% CI 0.02 to 0.33, p <0.000; nsVT:OR 0.17, 95% CI 0.06 to 0.50, p = 0.001 and OR 0.09, 95% CI 0.02 to 0.46, p = 0.003). The recurrence rate of malignant VTA was 33%. In conclusion, variety of VDR and malignant VTA were found during long-term follow-up in patients with ICA. During nearly a 5 years follow-up period, the recurrence rate of malignant VTA was considerable. fVPC, nsVT, and malignant VTA were most often found in patients with an ARVC.

5.
Case Rep Med ; 2019: 1384139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320904

RESUMO

We report a 37-year-old woman with an out-of-hospital cardiac arrest caused by ventricular fibrillation due to digenic inheritance of long QT syndrome type 2 (KCNH2 gene) and type 6 (KCNE2 gene). During hospitalization, prolonged QTc intervals and frequent episodes of ventricular tachyarrhythmias manifested. Genetic testing identified a mutation of the KCNH2 gene and an unclassified variant, most likely pathogenic, of the KCNE2 gene. This digenic inheritance is extremely rare.

6.
Cornea ; 38(6): e20-e21, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30939496
7.
Am J Cardiol ; 123(12): 1962-1966, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955864

RESUMO

Risk stratification is the most challenging part in management of patients with Brugada syndrome (BrS). Conduction delay in the right ventricular outflow tract (RVOT) is the major mechanism underlying ventricular tachyarrhythmia (VTA) in BrS. However, QRS duration was not useful in stratifying high-risk patients in large registries. Reconstructing the traditional 12-lead electrocardiogram into QRS vector magnitude can be used to quantify depolarization dispersion and identify high-risk BrS patients. The aim of the study is to test the significance of the QRSvm as a predictor for VTA in patients with BrS. In this retrospective cohort, we included 136 patients (47 ± 15 years, 66% male) who visited outpatient clinic for cardiogenetic screening. All medical records were examined, all 12- lead electrocardiograms were reconstructed into QRSvm using Kors' quasiorthogonal method and were assessed for the presence of electrocardiographic signs indicative of RVOT conduction delay including R wave sign, deep SI, SII >SIII pattern, and Tzou criteria. QRSvm was significantly lower in patients who either presented with VTA or developed VTA during follow-up (1.24 ± 0.35 vs 1.78 ± 0.42 mV, p < 0.001). Positive RVOT conduction delay signs occurred more frequently in symptomatic patients (20% vs 7%, p < 0.001).The area under receiver operator characteristic curve for QRSvm was 0.85 (95% confidence interval [CI] 0.77 to 0.92). Using QRSvm cutoff of 1.55 mV, sensitivity and specificity were 89% and 71%, respectively. Multivariate regression analysis showed that QRSvm and RVOT signs are independent predictors for VTA in BrS patients (QRS vector magnitude: odds ratio 3.68, 95% CI 2.4 to 6.2, p = 0.001; RVOT: odds ratio 2.6, 95% CI 1.4 to 4.9, p = 0.001). In conclusion, not only electrocardiographic signs indicative of RVOT conduction delay but also QRSvm can be used as a predictor for VTA events in BrS patients.


Assuntos
Síndrome de Brugada/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Adulto , Síndrome de Brugada/complicações , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Taquicardia Ventricular/etiologia
8.
Influenza Other Respir Viruses ; 13(4): 382-390, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30884185

RESUMO

BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. METHODS: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). RESULTS: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90-day mortality (propensity score-adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). CONCLUSIONS: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.


Assuntos
Infecções por Coronavirus/complicações , Estado Terminal , Ventilação não Invasiva/estatística & dados numéricos , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório do Adulto , Estudos Retrospectivos , Arábia Saudita , Falha de Tratamento , Resultado do Tratamento
9.
Molecules ; 24(5)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823358

RESUMO

Nanocomposites of natural bone that show some benefits in terms of both composition and microstructure were synthesized by an in situ precipitation method. Hydroxyapatite (Hap) was prepared from cost-effective precursors within chitosan (CS) dissolved in aqueous acetic acid solution. The nanocomposite was synthesized for the removal of brilliant green dye (BG) from a contaminated water solution. The compositional and morphological properties of the nanocomposite were studied by means of FTIR spectroscopy, X-ray diffraction (XRD), SEM, and TEM analysis. Batch experiments were carried out to investigate the effects of pH, contact time, and initial concentration, as well as the adsorbent dosage and zero point charge for the sorbent to determine a suitable medium for the adsorption process. The sorption models using Mories-Weber, Lagrange, and Bangham equations were used to identify the mechanism and reaction order. The isotherm model was carried out using Langmuir, Freundlich, and Dubinin-Radusekevisch-Kanager equations to calculate the adsorption capacity and type of adsorption. Thermodynamic parameters, enthalpy change (∆Ho), entropy change (∆So), and Gibbs free energy (∆Go) were evaluated. All of the results suggest the feasibility of using nanocomposites as a sorbent for brilliant green dye removal.


Assuntos
Quitosana/química , Durapatita/química , Nanocompostos/química , Compostos de Amônio Quaternário/química , Poluentes Químicos da Água/química , Purificação da Água , Adsorção
10.
Bioorg Chem ; 85: 399-412, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30665034

RESUMO

Reaction of 5-morphilinosulfonylisatin (1) with acetophenones (2a-e) afforded 3-hydroxy-3-substituted-2-oxoindoles 3a-e, when treated with acetic acid the expected 3-phenacylidene-2-oxoindoles 4a-d and 4-hydroxy-5'-(morpholinosulfonyl) spiro [chromene-2, 3'-indolin]-2'-one 6 were obtained. Isatin derivative (1) was stirred with cyano derivatives to produce the arylidines (7a-c), while under reflux condition, it gave pyrrolo[2,3-b]indoles (8, 9). Moreover, istain (1) reacted with pyrazolo-5-one or 3-substituted phenol in presence of malononitrile to afford spiroxindole derivatives (10a,b) and (11a,b). Also, compounds (10a,b) and (11a,b) were obtained through cyclization of (7a) with pyrazolo-5-one or 3-substituted phenol. The obtained compounds were identified by IR, 1H NMR, 13C NMR and elemental analysis. Anticancer activity against three cancer cell lines (HepG-2, HCT-116 and MCF-7) were evaluated using sulforhodamine B assay method. Compounds 4b, 4c, 7a, 7c and 9 showed broad spectrum anticancer activity on the three tested cell lines with IC50 values less than 10 µM. Cell cycle analysis was performed for the most promising derivatives, compounds 4b and 7c arrested HepG-2 cells at G2-M phase, while compounds 7a and 9 accumulated cells at G0-G1 phase, all of them induced apoptosis at priG1 phase in the range of (11.32-19.17%). Additionally compounds 4b, 7a and 9 showed more potent activity against EGFR than Lapatinib, their IC50 values are from 0.019 to 0.026 µM while IC50 of Lapatinib is 0.028 µM. Molecular docking studies were conducted to investigate the binding mode, amino acid interactions and free binding energy of these potent derivatives.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Receptores ErbB/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Indóis/síntese química , Indóis/metabolismo , Lapatinib/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/metabolismo
11.
Cornea ; 38(2): 189-193, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30499830

RESUMO

PURPOSE: To review the outcome of 3 techniques for managing type 2 bubbles (between Descemet's membrane [DM] and stroma) formed during big bubble (BB) deep anterior lamellar keratoplasty (DALK) in different corneal pathologies. METHODS: This is an interventional case series study of patients with type 2 bubbles formed during BB DALK. Three techniques to complete DALK are described: the first is a DM baring technique similar to Anwar's BB technique, the second is the microbubble incision technique to preserve the pre-Descemetic support to DM, and the third is done in eyes with combined type 1 and type 2 BB (mixed bubble), where the type 1 bubble is opened and surgery is completed avoiding the type 2 bubble. RESULTS: Thirty-one eyes of 31 patients were included. The DM baring technique has a high rate of conversion to penetrating keratoplasty (12 of 16 eyes). In the other 2 techniques (which did not bare DM), DALK could be completed in all 15 cases with intact DM. Double anterior chamber is a relatively common complication after type 2 BB, even with an intact DM. CONCLUSIONS: DM baring techniques should be avoided in eyes with type 2 BB. Instead, deep stromal dissection searching for an incomplete type 1 bubble or using one of the manual dissection techniques as a guide to the clear pre-Descemetic stroma is safer and more reliable.


Assuntos
Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Lâmina Limitante Posterior/cirurgia , Adulto , Substância Própria/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Pain Res ; 12: 61-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30588080

RESUMO

Purpose: The study aimed at the evaluation of the impact of intravenous (IV) dexamethasone on efficacy and duration of analgesia of paravertebral block (PVB) in patients undergoing modified radical mastectomy (MRM). Patients and methods: This randomized, double-blind controlled trial included 50 patients with breast cancer scheduled for unilateral MRM. Ultrasound-guided PVB was performed in out-of-plane technique. The technique was repeated at each segment from C7 to T6. The participants were randomly allocated to one of two groups. Group BD (n=25) received IV 8 mg dexamethasone diluted with 8 mL of normal saline to reach 10 mL solution, while Group B received IV 10 mL normal saline. Top-up local infiltration analgesia into the surgical field was performed by the surgeon if needed using lidocaine 1% intraoperatively. Propofol infusion of 50-100 µg/kg/min was maintained throughout the surgery. The time to administration of the first postoperative analgesic dose, pain intensity as visual analog scale (VAS) score, number of patients who required rescue morphine analgesia, total morphine consumption, postoperative nausea and vomiting (PONV) impact scale, and the overall satisfaction of patients with pain management were measured. Results: Fifty patients were randomized and analyzed. The time to first rescue analgesic dose was significantly longer in Group DB (P<0.001). The VAS scores were significantly lower in Group DB compared to Group B up to 12 hours postoperatively. Morphine consumption was lower in Group DB compared to Group B. PONV Impact Scale score was significantly higher in Group B. Conclusion: Systemic dexamethasone increased the efficacy and duration of the single-shot multilevel PVB in breast cancer surgery. Trial registration: ISRCTN registry, study ID: ISRCTN15920148.

13.
Clin Infect Dis ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31925415

RESUMO

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a; none received rIFN-ß1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

14.
PLoS One ; 13(11): e0206831, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30439974

RESUMO

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. AIM: We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. METHODS: Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012-9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. FINDINGS: Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. CONCLUSION: Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.


Assuntos
Infecções por Coronavirus/epidemiologia , Estado Terminal/epidemiologia , Infecção Hospitalar/epidemiologia , Pessoal de Saúde/estatística & dados numéricos , Doenças Profissionais/epidemiologia , Adulto , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Estado Terminal/terapia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/terapia , Infecção Hospitalar/virologia , Surtos de Doenças , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Doenças Profissionais/diagnóstico , Doenças Profissionais/terapia , Doenças Profissionais/virologia , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Taxa de Sobrevida
15.
J Cataract Refract Surg ; 44(12): 1431-1435, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30274845

RESUMO

PURPOSE: To compare the levels of aldose reductase (ALR) enzyme, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF) in the anterior lens capsule of diabetic versus nondiabetic patients. SETTING: Alexandria Main University Hospital, Alexandria, Egypt. DESIGN: Prospective case-control study. METHODS: The study enrolled patients undergoing cataract extraction and divided them into 3 groups: eyes that had proliferative diabetic retinopathy (PDR), eyes that had nonproliferative diabetic retinopathy (NPDR), and nondiabetic eyes. The anterior lens capsules were obtained by performing femtosecond laser-assisted capsulorhexis. Concentrations of ALR, ICAM-1, and VEGF in the lens capsule specimens were measured using human enzyme-linked immunosorbent assay. RESULTS: This study comprised 200 patients (200 eyes); 51 eyes had PDR, 49 eyes had NPDR, and 100 eyes were nondiabetic. The mean ALR, ICAM-1, and VEGF levels in the anterior capsule of diabetic group were 2.84 nanogram (ng)/mL ± 0.51 (SD), 87.73 ± 22.84 picogram (pg)/mL, and 75.53 ± 14.95 pg/mL, respectively; whereas, in the nondiabetic group, they were 1.44 ± 0.17 ng/mL, 35.45 ± 2.8 pg/mL, and 33.55 ± 5.47 pg/mL, respectively. In comparing the concentrations of these mediators, both the PDR and NPDR groups had significantly higher levels compared with the nondiabetic eyes (P < .001). In addition, eyes with PDR had significantly higher levels of these mediators than eyes with NPDR (P < .001). CONCLUSION: The concentrations of ALR, ICAM-1, and VEGF in the anterior lens capsule of diabetic patients are significantly higher than those of nondiabetics. A significantly higher level of 3 mediators in eyes with PDR compared with those with NPDR might allow the use of them as a biomarker for severity of diabetic retinopathy.


Assuntos
Aldeído Redutase/biossíntese , Cápsula Anterior do Cristalino/metabolismo , Catarata/metabolismo , Retinopatia Diabética/metabolismo , Molécula 1 de Adesão Intercelular/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Biomarcadores/metabolismo , Estudos de Casos e Controles , Catarata/complicações , Retinopatia Diabética/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
BMC Anesthesiol ; 18(1): 129, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30219027

RESUMO

BACKGROUND: Patients undergoing craniotomy operations are prone to various noxious stimuli, many strategies are commenced to provide state of analgesia, for better control of the stress response and to overcome its undesired effects on the haemodynamics and post-operative pain. Scalp nerves block are considered one of these strategies. This study was conceived to evaluate the effect of addition of hyaluronidase to the local anaesthetic mixture used in the scalp nerves block in patients undergoing elective craniotomy operations. METHODS: 64 patients undergoing elective craniotomy operations were enrolled in this prospective randomized, double-blind comparative study. Patients were randomly assigned to two groups. Group LA, patients subjected to scalp nerves block with 15 ml bupivacaine 0.5%, 15 ml lidocaine 2%, in 1:400000 epinephrine. Group H as Group LA with15 IU /ml Hyaluronidase. RESULTS: Patients in the H group showed lower VAS values for 8 h postoperative, compared to the LA group. The haemodynamic response showed lower values in the H group, compared to the LA group. Those effects were shown in the intraoperative period and for 6 h post-operative. No difference was detected regarding the incidence of complications nor the safety profile. CONCLUSION: Our data supports the idea that addition of hyaluronidase to the local anesthetic mixture improves the success rates of the scalp nerves block and its efficacy especially during stressful intraoperative periods and in the early postoperative period. No evident undesirable effects in relation to the addition of hyaluronidase. TRIAL REGISTRATION: Clinical Trial registry on ClinicalTrials.gov , NCT 03411330 , 25-1-2018.


Assuntos
Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Craniotomia/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Hialuronoglucosaminidase/administração & dosagem , Lidocaína/administração & dosagem , Bloqueio Nervoso/métodos , Adulto , Craniotomia/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Couro Cabeludo/efeitos dos fármacos , Couro Cabeludo/inervação , Resultado do Tratamento
17.
Eur J Med Chem ; 156: 918-932, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30096580

RESUMO

New series of 5-(morpholinosulfonyl) isatin derivatives were designed and synthesized. The new compounds were characterized on the basis of spectral and elemental analyses. They were examined for their cytotoxic effects using SRB assay on four cancer cell lines HepG2, HCT116, CACO and MCF-7 in addition to the non-cancerous human cell line. They were non cytotoxic towards the normal derived cell line (IC50 value > 130 µM). Compounds 3, 6, 10 and 11 showed IC50 values less than 10 µM on three of the tested cell lines HepG2, HCT116 and CACO. Compounds 2h, 5, and 7b showed IC50 values less than or nearly equal 10 µM on HepG2, CACO and HCT116 respectively. Compounds 3 and 6 revelaed IC50 values less than 12 µM on MCF7. These obtained IC50 values are comparable with that of doxrubicin as it has showed IC50 range from 4.5 to 8.28 µM on the tested cell lines. All these promising derivatives showed inhibitory activity against EGFR with IC50 values less than 2 µM. The most potent EGFR inhibitors 7b (IC50 = 46 nM) and 10 (IC50 = 23 nM) showed to cause cell cycle arrest at G2/M phase and induce apoptosis. Molecular docking studies also were simulated to put insight and make better understanding to their structural features.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Isatina/análogos & derivados , Isatina/farmacologia , Neoplasias/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
18.
Urol Ann ; 10(3): 291-295, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30089988

RESUMO

Aims: The aim of this study is to compare between transrectal ultrasound (TRUS)-guided aspiration and transurethral (TU) deroofing in the treatment of prostatic abscess regarding safety and efficacy. Settings and Design: This prospective randomized study was done during the period between April 2009 and March 2015 and included 32 patients with prostatic abscess. Subjects and Methods: All patients were enrolled in the study after obtaining a written informed consent and approval of the local ethical committee. The patients were randomly allocated into two groups; Group A treated by TRUS-guided aspiration, saline wash, and local injection of antibiotics and Group B treated by TU deroofing of the abscess. All patients received broad-spectrum antibiotics during the period of treatment, and the follow-up was done on the 5th day by TRUS to ensure complete resolution of the abscess. Statistical Analysis Used: Statistical analysis was done using online social science statistical calculators http://www.socscistatistics.com/Default.aspx using t-test for two independent means, Chi-square test, and Mann-Whitney U-test with P < 0.05 considered statistically significant. Results: The mean age was 59 ± 11.46 and 60 ± 13.65 years for Groups A and B, respectively. Diabetes mellitus was detected in 9 (56.25%) and 6 (37.5%) patients in Groups A and B, respectively, hypertension in 7 (43.75%) and 6 (37.5%) patients in Groups A and B, respectively, and two patients (12.5%) with liver cirrhosis in each group. The mean size of the abscess was 3.36 ± 0.86 and 3.04 ± 0.86 cm in Groups A and B, respectively (P = 0.29). The abscess recurred in five patients (31.25%) and one patient (6.25%) in Groups A and B, respectively (P = 0.08). TRUS-guided aspiration was done for all recurrent cases except for two patients (12.5%) in Group A required trans urethral deroofing of the recurrent abscess. The mean hospital stay was 12.9 ± 4.05 and 7.25 ± 2.40 days for Groups A and B, respectively (P = 0.000). In Group A, one patient (6.25%) was complicated by urethrorectal fistula, whereas in Group B, one patient (6.25%) was complicated by septic shock, three patients (13.75%) with epididymo-orchitis and two patients (12.5%) with urethral stricture. Conclusion: Patients with prostatic abscess treated with TRUS-guided aspiration show less morbidity, higher recurrence rate, and longer hospital stay than those treated with TU deroofing.

19.
J Egypt Natl Canc Inst ; 30(3): 117-122, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29958780

RESUMO

INTRODUCTION: About 50% of patients with cancer develop bone metastasis mainly presenting with distressing, drug-resistant pain. AIM OF THE WORK: The study evaluated efficacy and safety of combined cementoplasty and bony radiofrequency ablation in palliation of intractable pain and disability in cancer patients with bony metastases. PATIENTS AND METHODS: The study included 30 adult patients suffering from localized bony metastases causing refractory moderate to severe pain. Radiofrequency bony ablation performed followed by cementoplasty were done under computed tomography (CT) guidance with conscious sedation and local anesthesia. Final CT check was done to ensure adequate lesion filling and to exclude any cement leakage. Pain, hemodynamic variables, and neurological status were checked for a minimum of 2 h before discharge. The patients were followed up weekly in the pain clinic. The primary outcome measures pain severity and daily opioid consumption. The secondary outcome measures were quality of life and the degree of disability, and procedure-related adverse outcomes. RESULTS: Pain score, daily morphine consumption, and Oswestry Disability Index score decreased significantly after 1 day, and 1, 4 and 12  weeks. None of the patients had serious complications during the postoperative follow up visits. Only 4 patients (13.3%) experienced discomfort during, and few days after the procedure, 3 patients (10%) suffered from local infection, and 2 patients (6.7%) reported cement leakage. CONCLUSION: Combined radiofrequency ablation and cementoplasty is a safe and effective pain relief modality in patients suffering from extraspinal painful bone metastases with improvement of the quality of life.


Assuntos
Neoplasias Ósseas/radioterapia , Ablação por Cateter , Cementoplastia , Dor/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Ceftriaxona/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/complicações , Dor/diagnóstico por imagem , Dor/patologia , Manejo da Dor , Cuidados Paliativos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
J Cardiovasc Electrophysiol ; 29(7): 998-1003, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29608225

RESUMO

BACKGROUND: Brugada syndrome (BrS) is an autosomal dominant disease responsible for sudden cardiac death in young individuals without structural anomalies. The most critical part in the management of this channelopathy is identification of high-risk patients, especially asymptomatic subjects. Prior studies have shown that conduction delay in the right ventricular outflow tract (RVOT) is the main mechanism for developing ventricular tachyarrhythmia (VTA) in BrS patients. The aim of this study was to investigate the significance of electrocardiographic RVOT conduction delay parameters as predictors for development of VTA in patients with BrS. METHODS AND RESULTS: We retrospectively analyzed electrocardiograms obtained from 147 BrS patients (43 ± 15 years, 65% men) and assessed the following electrocardiographic parameters: (1) Tzou criteria (V1R > 0.15 mV, V6S > 0.15 mV, and V6S:R > 0.2), (2) prominent S wave in lead I, lead II, and lead III, (3) SII > SIII, and (4) prominent Q wave in lead III as possible predictors of VTA occurrences during follow-up. Prominent SI, SII, SIII, SII > SIII, QIII, and +ve Tzou criteria occurred more frequently in patients who either presented with VTA or developed VTA during the follow-up of 56 (IQR: 40-76) months. SII > SIII has the highest area under the curve for prediction of VTA (AUC: 0.84, sensitivity: 80%, specificity: 89%). Multivariable regression analysis showed that prominent S waves in lead I, SII > SIII and +ve Tzou criteria are independent predictors for VTA in BrS patients. CONCLUSION: Prominent S in lead I, SII > SIII and +ve Tzou criteria can be used as effective signs for predicting VTA in patients with BrS.


Assuntos
Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Adulto , Síndrome de Brugada/epidemiologia , Eletrocardiografia/tendências , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taquicardia Ventricular/epidemiologia , Obstrução do Fluxo Ventricular Externo/epidemiologia
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