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1.
J Family Med Prim Care ; 12(4): 679-685, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37312778

RESUMO

Background: The government of Saudi Arabia implemented a law to enforce the law and regulations prohibiting the dispensing of antibiotics without a prescription, and studies have been conducted to assess the impact of such a law in Saudi Arabia. However, the extent to which law enforcement has changed the perceptions and attitudes of health care professionals, mainly physicians, toward antibiotic resistance is unknown in Saudi Arabia. Material and Methods: A cross-sectional study was conducted in Riyad, Saudi Arabia, on 378 physicians. These physicians were mainly working in primary care centers. An online questionnaire was sent to the physicians, and it consisted of 35 items and was divided into four sections: 6 items were on sociodemographic characteristics of participants; 13 items were on the knowledge of physicians about antibiotic resistance; 8 items were on the attitude the physicians toward enforcement law, and the final 8 items were on the attitude the patients toward enforcement law in an outpatient setting. Results: Around 90% of the physicians acknowledged that physicians should stop prescribing antibiotics without indication. About 29.1 % of the physicians agreed, and 56.3% showed strong agreement that law enforcement is for the patient's benefit. Similarly, 33.6% agreed, and 50.8% strongly agreed that law enforcement limits the resistance of bacteria. Around 24.3% of the patients disagreed, and 23% strongly disagreed that law enforcement does not affect anything. Around one-third of the physicians (34.4%) agreed, and 23.5% strongly agreed that the new regulation of law enforcement of antibiotic prescription increases public awareness regarding the misuse of antibiotics. Conclusion: It seems that law enforcement has impacted the knowledge and attitude of physicians as they agree with law enforcement and its associated benefits for patients. They also acknowledged that law enforcement could limit the resistance to bacteria. However, not all physicians agree that law enforcement has an effect on anything, and new regulation of antibiotic prescription law increases public awareness regarding the misuse of antibiotics.

2.
Cureus ; 14(11): e31036, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36475135

RESUMO

Background During and after the coronavirus disease 2019 (COVID-19) pandemic, there was a significant increase in the demand for aesthetic procedures nationwide. We believe that one of the factors contributing to this increase was the use of video conferencing apps. Therefore, the purpose of this study was to analyze the aesthetic concerns that were identified by video conferencing. Methodology In Saudi Arabia, an observational, cross-sectional study was conducted from February to April, 2022. An online survey was used to assess the aesthetic concerns raised by video conferencing. The survey addressed multiple aspects, including demographic data, information on video call utilization, the attentional focus of the participants during video calls, and new appearance concerns identified on video calls. Results The survey successfully captured 432 adult participants. More than 85% of participants disliked at least one character of their appearance during video conferencing. The skin color type (based on the Fitzpatrick scale), time spent on video calls, and visual focus during the virtual meeting were significantly correlated with self-perception of new disliked features. Conclusion Video conferencing showed a significant statistical correlation with identified disliked facial/body features in both genders. People with skin color type III were less likely to perceive a disliked feature through video conferencing applications. The likelihood of having a disliked feature was significantly higher among individuals who spent up to one hour per day using video calls. Additionally, those who mainly paid attention to their face or body during virtual meetings were more likely to have disliked features.

3.
TH Open ; 6(4): e396-e407, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36452200

RESUMO

The vascular obstructive thrombus is composed of a mesh of fibrin fibers with blood cells trapped in these networks. Enhanced fibrin clot formation and/or suppression of fibrinolysis are associated with an increased risk of vascular occlusive events. Inhibitors of coagulation factors and activators of plasminogen have been clinically used to limit fibrin network formation and enhance lysis. While these agents are effective at reducing vascular occlusion, they carry a significant risk of bleeding complications. Fibrin clot lysis, essential for normal hemostasis, is controlled by several factors including the incorporation of antifibrinolytic proteins into the clot. Plasmin inhibitor (PI), a key antifibrinolytic protein, is cross-linked into fibrin networks with higher concentrations of PI documented in fibrin clots and plasma from high vascular risk individuals. This review is focused on exploring PI as a target for the prevention and treatment of vascular occlusive disease. We first discuss the relationship between the PI structure and antifibrinolytic activity, followed by describing the function of the protein in normal physiology and its role in pathological vascular thrombosis. Subsequently, we describe in detail the potential use of PI as a therapeutic target, including the array of methods employed for the modulation of protein activity. Effective and safe inhibition of PI may prove to be an alternative and specific way to reduce vascular thrombotic events while keeping bleeding risk to a minimum. Key Points Plasmin inhibitor (PI) is a key protein that inhibits fibrinolysis and stabilizes the fibrin network.This review is focused on discussing mechanistic pathways for PI action, role of the molecule in disease states, and potential use as a therapeutic target.

4.
Pharmaceuticals (Basel) ; 15(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36145281

RESUMO

The aggressive triple-negative breast cancer (TNBC) is a challenging disease due to the absence of tailored therapy. The search for new therapies involves intensive research focusing on natural sources. Achillea fragrantissima (A. fragrantissima) is a traditional medicine from the Middle East region. Various solvent extracts from different A. fragrantissima plant parts, including flowers, leaves, and roots, were tested on TNBC MDA-MB-231 cells. Using liquid chromatography, the fingerprinting revealed rich and diverse compositions for A. fragrantissima plant parts using polar to non-polar solvent extracts indicating possible differences in bioactivities. Using the CellTiter-Glo™ viability assay, the half-maximal inhibitory concentration (IC50) values were determined for each extract and ranged from 32.4 to 161.7 µg/mL. The A. fragrantissima flower dichloromethane extract had the lowest mean IC50 value and was chosen for further investigation. Upon treatment with increasing A. fragrantissima flower dichloromethane extract concentrations, the MDA-MB-231 cells displayed, in a dose-dependent manner, enhanced morphological and biochemical hallmarks of apoptosis, including cell shrinkage, phosphatidylserine exposure, caspase activity, and mitochondrial outer membrane permeabilization, assessed using phase-contrast microscopy, fluorescence-activated single-cell sorting analysis, Image-iT™ live caspase, and mitochondrial transition pore opening activity, respectively. Anticancer target prediction and molecular docking studies revealed the inhibitory activity of a few A. fragrantissima flower dichloromethane extract-derived metabolites against carbonic anhydrase IX, an enzyme reported for its anti-apoptotic properties. In conclusion, these findings suggest promising therapeutic values of the A. fragrantissima flower dichloromethane extract against TNBC development.

5.
Front Genet ; 13: 886038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035137

RESUMO

Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD and related traits in Saudi kidney disease patients. We applied a genetic testing approach using a targeted next-generation sequencing gene panel including 102 genes causative or associated with CKD. A total of 1,098 Saudi participants were recruited for the study, including 534 patients with ESRD and 564 healthy controls. The pre-validated NGS panel was utilized to screen for genetic variants, and then, statistical analysis was conducted to test for associations. The NGS panel revealed 7,225 variants in 102 sequenced genes. Cases had a significantly higher number of confirmed pathogenic variants as classified by the ClinVar database than controls (i.e., individuals with at least one allele of a confirmed pathogenic variant that is associated with CKD; 279 (0.52) vs. 258 (0.45); p-value = 0.03). A total of 13 genetic variants were found to be significantly associated with ESRD in PLCE1, CLCN5, ATP6V1B1, LAMB2, INVS, FRAS1, C5orf42, SLC12A3, COL4A6, SLC3A1, RET, WNK1, and BICC1, including four novel variants that were not previously reported in any other population. Furthermore, studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.

6.
Pediatr Cardiol ; 43(2): 308-323, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34495353

RESUMO

Residual or iatrogenic ventricular septal defects (VSDs) may result in significant hemodynamic effect. This study aimed to review our center experience in transcatheter closure of post-surgical and post-intervention residual and iatrogenic VSDs and to report on their 12-month long-term outcome. All patients who underwent transcatheter closure of residual/iatrogenic VSDs after surgical or transcatheter CHD interventions between January-2015 and January-2020 were included. Patients' medical records were reviewed and analyzed. Twenty-three patients with a mean age of 14.3 ± 8.8 years were included. The VSD was residual in 18 (78.3%) patients and iatrogenic in 5 (21.7%) patients, post-operative in 19 (82.6%) patients and post-transcatheter in 4 (17.4%) patients. The VSD site was peri-membranous in 9 (39.1%) patients, high-muscular in 6 (26.1%) patients, mid-muscular in 4 (17.4%) patients, and Gerbode shunt in 4 (17.4%) patients. The QP/QS ratio was 2.5 ± 0.7, and the VSD diameter was 6.1 ± 2.1 mm. Most, 16 (71.43%) patients underwent antegrade device deployment, and 7 (28.57%) patients underwent retrograde transaortic device deployment with 3 (13.0%) patients required two devices. Amplatzer™ Muscular VSD devices were used in 16 (69.6%) patients, Amplatzer™ Duct occlude-I devices were used in 4 (17.4%) patients, and Amplatzer™ Duct Occluder-II devices were used in 3 (13.0%) patients with a mean device size of 8.8 ± 2.8 mm. Procedural and fluoroscopy times were 55.1 ± 16.2 and 16.3 ± 4.0 min respectively. During follow-up (23.3 ± 15.9 months), no patient required re-intervention or exhibited mortality. Transcatheter closure of post-operative and post-intervention residual/iatrogenic VSDs represents a safe, feasible, and effective therapeutic approach.


Assuntos
Comunicação Interventricular , Dispositivo para Oclusão Septal , Adolescente , Adulto , Cateterismo Cardíaco/efeitos adversos , Criança , Pré-Escolar , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/cirurgia , Humanos , Doença Iatrogênica , Estudos Retrospectivos , Dispositivo para Oclusão Septal/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
Struct Heart ; 6(3): 100043, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37274546

RESUMO

Background: In specific patients with severe mitral regurgitation (MR), mitral valve (MV) pathology is unique and requires creative transcatheter repair techniques. This study aimed to evaluate the feasibility and safety of a new transcatheter MV repair technique, using occluder devices in symptomatic high-surgical-risk patients with severe MR, either due to MV leaflet (MVL) perforations or due to post-clips residual MR, and to report on their 6-month outcomes. Methods: The study enrolled all high-risk patients with severe MR due to MVL perforations and post-clips residual MR who underwent transcatheter MV repair using occluder devices, from November 2016 to August 2019. Results: The study enrolled 16 patients; 9 (56.25%) with MVL perforations and 7 (43.75%) with post-MitraClip (Abbott Laboratories, Abbott Park, Illinois) residual MR, with a mean age of 55.75 ± 16.69 years. Mean perforation/jet diameters were 5.75 ± 1.67 and 6.5 ± 1.93 mm, and the mean 3D-vena contracta area was 0.54 ± 0.14 cm2. Perforations were crossed retrograde (transaortic in 7 [43.75%] patients and transapical in 2 [12.5%] patients), and post-MitraClip devices residual jets were crossed antegrade (transvenous/transseptal). Six (37.5%) patients required arteriovenous loop formation for device deployment, that was antegrade transvenous/transseptal in 13 (81.25%) patients and retrograde transapical in 3 (18.75%) patients. Devices used were Amplatzer-ASO in 10 (62.5%) patients and Amplatzer-VP-II in 6 (37.5%) patients. Mean procedural and fluoroscopy times were 55.13 ± 16.24 and 16.25 ± 4.03 â€‹minutes, respectively. Patients passed successfully, without MV gradient change or device-related complications. Conclusions: Transcatheter MV repair of MVL perforations/post-clips residual MR is a new, feasible, and safe technique for high-surgical-risk patients.

8.
Am J Case Rep ; 22: e931013, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407064

RESUMO

BACKGROUND Button batteries (BBs) can be inhaled or swallowed accidentally, particularly by infants and children, who can present as a surgical emergency with a fatal outcome. This report is of a case of a 2-year-old boy who developed an aortoesophageal fistula (AEF) after swallowing a button battery and was successfully treated using a novel vascular plug device as a bridge to definitive surgical repair. AEF is diagnosed using computed tomography angiography (CTA), after laparotomy, and using aortography. Aortic endovascular stenting and vascular occluder placement is a minimally invasive emergency option until definitive treatment can be provided. The surgical options include repair the aortic defect primarily, or the diseased segment of the aorta is replaced with a graft. CASE REPORT A 2-year-old boy presented with hematemesis 9 days after ingestion of a button battery, which was removed endoscopically 16 hours after the incident. The patient was resuscitated aggressively and diagnosed to have AEF using computed tomography angiography (CTA). The aorta was successfully repaired using a vascular plug device, which kept the patient safe until the definitive surgical treatment was done 2 months later. The defect was repaired with direct anastomosis and completed with a patch of bovine pericardium, as well as closure of the fistula from the esophageal side with stitches. CONCLUSIONS This report presents a rare but previously reported complication of swallowing a button battery, resulting in an aortoesophageal fistula. The aorta was successfully repaired using a vascular plug as a minimally invasive emergency option, which is considered as a lifesaving procedure and a bridge for definitive repair.


Assuntos
Doenças da Aorta , Implante de Prótese Vascular , Fístula Esofágica , Fístula Vascular , Doenças da Aorta/etiologia , Doenças da Aorta/cirurgia , Pré-Escolar , Deglutição , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Humanos , Masculino , Fístula Vascular/etiologia , Fístula Vascular/cirurgia
9.
Saudi Pharm J ; 29(5): 361-368, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34135662

RESUMO

Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies have been reported on potential modulation effects of these resin extracts on drug metabolism. Therefore, we studied C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The C. myrrha extracts were prepared by sonication and boiling, resembling the most popular traditional preparations of maceration and decoction, respectively. Both boiled and sonicated aqueous extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with these aqueous extracts was determined using CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic CYP isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were assessed using reverse transcription-quantitative polymerase chain reaction and Western blot technologies. The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha boiled and sonicated aqueous extracts. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of the dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold in HepG2 cells treated with either boiled or sonicated C. myrrha aqueous extracts tested between 1 and 30 µg/ml, as compared with the untreated cells. However, CYP3A4 mRNA expression level exceeded the 2.0-fold cutoff when the cells were exposed to 30 µg/ml of C. myrrha extracts. The up-regulation of CYP mRNA expression levels induced by both boiled and sonicated C. myrrha aqueous extracts was confirmed at the CYP protein expression levels. In conclusion, both sonicated and boiled C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for CYP isoenzyme activity assessment and the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.

10.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34043590

RESUMO

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.


Assuntos
COVID-19/genética , COVID-19/imunologia , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Mutação com Perda de Função , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Fator Regulador 7 de Interferon/genética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Receptor 3 Toll-Like/genética , Sequenciamento do Exoma , Sequenciamento Completo do Genoma , Adulto Jovem
11.
J Saudi Heart Assoc ; 33(4): 306-312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35083122

RESUMO

BACKGROUND: Systemic to pulmonary shunt (Shunt) is offered for children with duct dependent pulmonary circulation to augment pulmonary flow. Recently patent ductus arteriosus (PDA) stent (Stent) is widely used as an alternative method. We aimed to compare post intervention outcomes in children underwent either procedure. METHODS: Infants under 3 months who had an initial palliation by Shunt or Stent were retrospectively reviewed between 2008 and 2016, then followed till the second intervention or 1 year whichever earlier. RESULTS: 187 patients (110 Shunt and 77 Stent) were included. Initial weight and pulmonary artery (PA) branches size were similar between the groups. Shunt patients had more shock preoperatively and required more emergency intervention. Stent group showed less ICU stay 4 (1-8) vs 13 (7-23) days, p < 0.0001 and less positive pressure ventilation days 1 (0-2) vs 5.5 (3-11), p < 0.0001. However, Stent group had more symptomatic arterial and deep venous thromboses. In Stent patients the branch PAs growth was better and more homogeneous. At follow-up, no difference between groups regarding cumulative readmission days to hospital, hemoglobin levels and the weight percentile for age. Mortality was not different with a tendency to be higher in the Shunt group (13%) compared to the Stent group (5%), p 0.1. CONCLUSIONS: The implantation of PDA stent in patients with duct dependent pulmonary circulation results in a smoother ICU course and a shorter hospital stay, with higher risk of vascular injury. Shunt and Stent procedures have a good outcome for PA growth, somatic growth and survival.

12.
Clin Lab ; 66(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33337826

RESUMO

BACKGROUND: Diabetes mellitus is a chronic illness that is a worldwide issue. HbA1c has been used to monitor glycemic control in patients with diabetes for many years. Although HbA1c measurement is needed for calculating estimated average blood glucose (eAG), it is now recommended that eAG is used instead of HbA1c for expression of blood glucose control and communication with patients and health care providers. This study, investigated fasting blood glucose (FBS) as an indicator of overall chronic blood sugar control by assessing the correlation between FBS with eAG derived from HbA1c. METHODS: The blood samples for HbA1c assay were collected in EDTA tubes and were analyzed by an HPLC analyzer (G8 Tosoh, Japan). Blood samples for FBS were collected in serum separator tubes, transported, and centrifuged for 15 minutes at 3,000 g. FBS levels were determined in serum samples with the enzymatic hexokinase method by a clinical chemistry analyzer (Architect 8000, Abbott, USA). RESULTS: Statistical analysis was performed on 1,740 patients with type 2 diabetes mellitus with HbA1c levels above 6.5 mmol/L. The difference between FBS (9.3 ± 3.7 mmol/L) and eAG (11.14 ± 2.7 mmol/L) was statistically signif-icant (p < 0.0001). The correlation coefficient between FBS and eAG was r = 0.65 (95% CI; 0.62 - 0.69), with a p-value < 0.0001. While the correlation coefficient between FBS and eAG at HbA1c < 6.5% was r = 0.251 (95% CI, 0.16 - 0.34), with a significant p-value of < 0.00001. The combined data, standard deviation (SD), median, and interquartile range of eAG and FBS for all of the diabetic groups (n = 2,315), were 10.1 ± 3.00 mmol/L, 9.5 mmol/L, and 7.75 - 12.03 mmol/L for eAG, respectively. Similarly, these values were 8.5 ± 3.6 mmol/L, 7.5 mmol/L, and 6.0 - 10.00 mmol/L for FBS, respectively. CONCLUSIONS: We concluded that there is a moderate and significant positive correlation between fasting blood sugar and the estimated average blood glucose derived from HbA1c. Although FBS might be helpful for daily monitoring of diabetes. Further studies must be conducted to provide solid results to support that FBS and its derived variable eAG can replace HbA1c as an indicator of long-term overall control of T2DM patients.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/diagnóstico , Jejum , Hemoglobinas Glicadas/análise , Humanos , Japão
13.
J Saudi Heart Assoc ; 32(2): 149-156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154909

RESUMO

INTRODUCTION: Pediatric cardiac catheterization interventions become an established way of care for selected patients with congenital heart diseases. Cardiac catheterization for neonates and small infants can be challenging. The indications for diagnostic cardiac catheterization have decreased with the advent of advanced non-invasive imaging modalities. PATIENTS AND METHOD: Between June 2012 and July 2017 patients less than three months who had cardiac catheterization in two centers were reviewed. RESULTS: During the study period, 174 patients underwent interventional cardiac catheterization,83.3% of them had CHD with two-ventricle circulation and 29 patients (16.7%) had single ventricle pathophysiology. Procedures include diagnostic cath, BAS, balloon pulmonary and aortic valvuloplasty, coarctation angioplasty, and stenting procedures. The vascular access depends upon the type of procedure. All except one had general anesthesia. ICU admission was required on 106 patients (62%). Patients were divided according to the type of cardiac lesion (single versus biventricular pathology) as well as according to the type of intervention (stenting and non-stenting procedures). Comparing these groups revealed that: stent procedures and procedures for patients with single ventricle pathologies were performed at an earlier age, with more contrast, fluoro and procedure time than for non-stent procedures and procedures for patients with biventricular pathologies. Complications include transient arrhythmias in most patients, perforation of the RVOT in one and lower limb hypoperfusion in 12 patients. ICU complications include low cardiac output symptoms (LCOS) in 10 (7%), and sepsis in 8. No intra-procedure mortality. The overall survival was 94%. Ten patients died, with one early and 9 late mortality. 60% of the dead patients had PDA stenting. Reintervention varies according to the patient's diagnosis. CONCLUSION: Cardiac catheterization intervention an important modality in the management of neonates and infants with critical CHD. Well planned procedures and team expertise are essential. Stenting procedures and procedures for patients with single ventricles carries higher morbidity and mortality.

14.
Pharmaceutics ; 12(7)2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679809

RESUMO

PURPOSE: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer-lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. METHODS: ANS loaded PEGylated polymer-lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. RESULTS: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from -0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. CONCLUSION: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.

15.
Saudi Med J ; 40(4): 367-371, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30957130

RESUMO

OBJECTIVES: We studied these predictors at a single cardiac center. Methods: A retrospective cohort study was carried out after obtaining approval from the institutional review board. All patients (age, 0-14 years) who underwent  congenital heart disease (CHD)  surgery from January 2014 to June 2016 were included. Prolonged mechanical ventilation (PMV)  was defined as greater than 72 hours of ventilation. Results: A total of 257 patients were included, among whom 219 (85.2%) were intubated for greater than 72 hours and 38 (14.8%) were intubated for ≥72 hours. Age (29.9 versus 11.95 years), weight (9.6 versus 5.9 kg), cross-clamp time (CCT) (53.6 versus 71.8 min), cardiopulmonary bypass time (CBP) (80.98 versus 124.36 min), length of stay in the pediatric intensive care unit (PICU) (10.4 versus 27.2 days), infection (12.8% versus 42.1%), open sternum (0.9% versus 13.2%), re-intubation (19.2% versus 39.5%), pulmonary hypertension (10.9% versus 31.6%), and impaired heart function (10.1% versus 23.7%) were associated with PMV. In terms of Risk Adjustment in Congenital Heart Surgery (RACHS) classification, only patients with RACHS 4 (18.4%) were associated with the risk for PMV. Conclusions: Age, weight, CBP, CCT, pulmonary hypertension, impaired cardiac function, and sepsis are risk factors for PMV. These factors should be considered when deciding surgery and in providing PICU care.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Respiração Artificial/efeitos adversos , Adolescente , Fatores Etários , Peso Corporal , Ponte Cardiopulmonar , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação , Masculino , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Sepse , Fatores de Tempo
16.
Int J Nanomedicine ; 13: 199-208, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29343958

RESUMO

PURPOSE: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a treatment for breast cancer in postmenopausal women. Despite the wide use of ANS, it is associated with serious side effects due to uncontrolled delivery. In addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology-based drug delivery has the potential to enhance the efficacy of drugs and overcome undesirable side effects. In this study, we aimed to prepare novel ANS-loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response of MCF-7 cell line to both ANS and ANS-loaded NPs. METHOD: ANS-NPs were synthesized using double emulsion method and characterized using different methods. The apoptotic response was evaluated by assessing cell viability, morphology, and studying changes in the expression of MAPK3, MCL1, and c-MYC apoptotic genes in MCF-7 cell lines. RESULTS: ANS was successfully encapsulated within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation efficiency of 67%, particle size of 186±27.13, and a polydispersity index of 0.26±0.11 with a sustained release profile extended over 144 hours. In addition, results for cell viability and for gene expression represent a similar apoptotic response between the free ANS and ANS-NPs. CONCLUSION: The synthesized ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a rationale to pursue pre-clinical evaluation of ANS-NPs on animal models.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores da Aromatase/administração & dosagem , Nanopartículas/administração & dosagem , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Anastrozol , Apoptose/genética , Inibidores da Aromatase/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Meia-Vida , Humanos , Células MCF-7 , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Nanopartículas/química , Nitrilas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Proteínas Proto-Oncogênicas c-myc/genética , Solubilidade , Triazóis/química
17.
Heart Lung Circ ; 17(2): 148-51, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17350890

RESUMO

Coronary artery to coronary sinus fistula (CACSF) in association with stenosis of coronary sinus (CS) ostium and retrograde drainage via persistent left superior vena cava (LSVC) is an extremely rare anomaly presenting in the neonatal period. We report herein a 2-day-old boy with similar anomalies, who presented to us with congestive heart failure and underwent surgical repair. Echocardiography including Doppler ultrasound was a non-invasive, quick and accurate tool to diagnose each abnormality satisfactorily. This anomaly has clinical, physiological and surgical implications due to presence of altered flow pattern and variable anatomy. Therefore, such malformations need a careful assessment, preferably by non-invasive diagnostic tools, and appropriate management.


Assuntos
Fístula Artério-Arterial/congênito , Seio Coronário/anormalidades , Anomalias dos Vasos Coronários/complicações , Vasos Coronários , Insuficiência Cardíaca/etiologia , Fístula Artério-Arterial/cirurgia , Procedimentos Cirúrgicos Cardíacos , Anomalias dos Vasos Coronários/cirurgia , Eletrocardiografia , Comunicação Interatrial/cirurgia , Humanos , Recém-Nascido , Masculino
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