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Background: Parkinson's disease (PD) is one of the major neurodegenerative disorders and the prevalence is expected to increase during the next couple of decades. There is a need for safe and effective therapeutic regimen that can effectively manage this neurotoxicity. The leaves and several other parts of Cordia dichotoma are known to possess number of medicinal properties. The purpose of this study was to examine the neuroprotective role of Cordia dichotoma in an experimental model of haloperidol-induced P.D. Materials and methods: Five groups of rats were randomly assigned into different groups. Intraperitoneal haloperidol 1 mg/kg was given to the inducer group and 0.5% CMC to the normal control. The reference standard was syndopa 10 mg/kg, p.o., and the test group animals received C. dichotoma's ethanolic extract at 200 and 400 mg/kg orally for one week. Rats exposed to haloperidol were assessed for behavioral, neurochemical, and histopathological parameters. Results: C. dichotoma leaves extract dose-dependently increased behavioral activity and muscle coordination. The extract at 400 mg/kg was found to increase significantly (P < 0.001) the central square activity in open-field test, compared to haloperidol treated rats. In stepping test, both tested doses of C. dichotoma (200 mg and 400 mg/kg) were found to significantly (P < 0.001) reduce akinesia, besides these doses also decreased the catatonic responses induced by haloperidol. Further, the extraction treatment (200 mg and 400 mg/kg) significantly (P < 0.001) decreased malonaldehyde and increased antioxidant enzymes like catalase compared to the control group. Histopathological changes in the test group showed a significant reduction in haloperidol damage to normal morphology in cortical, hippocampus, substantia nigra, and pyramidal. Conclusion: The observations of the study suggest that Cordia dichotoma attenuated the haloperidol-induced neurological changes, indicating that the plant might benefit in the treatment of Parkinson's disease. The activity of Cordia dichotoma could be linked to its antioxidant property. Since, the drug is traditionally used in different parts of world; it could be a promising agent if more research establishes its safety and efficacy in other experimental models of Parkinson's Disease.
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In the present work, novel modality for lung cancer intervention has been explored. Primary literature has established the potential role of cyclooxygenase-2 (COX-2) inhibitor in regression of multiple forms of carcinomas. To overcome its poor water solubility and boost anticancer activity, etoricoxib (ETO) was chosen as a therapeutic candidate for repurposing and formulated into a nanoemulsion (NE). The prepared ETO loaded NE was characterized for the surface charge, droplet size, surface morphology, and in vitro release. The optimized ETO loaded NE was then investigated for its anticancer potential employing A549 lung cancer cell line via cytotoxicity, apoptotic activity, mitochondrial membrane potential activity, cell migration assay, cell cycle analysis, Caspase-3, 9, and p53 activity by ELISA and molecular biomarker analysis through RT-PCR test. The developed ETO-NE formulation showed adequate homogeneity in the droplet size distribution with polydispersity index (PDI) of (0.2 ± 0.03) and had the lowest possible droplet size (124 ± 2.91 nm) and optimal negative surface charge (-8.19 ± 1.51 mV) indicative of colloidal stability. The MTT assay results demonstrated that ETO-NE exhibited substantial anticancer activity compared to the free drug. The ETO-NE showed a substantially potent cytotoxic effect against lung cancer cells, as was evident from the commencement of apoptosis/necrotic cell death and S-phase cell cycle arrests in A549 cells. The study on these molecules through RT-PCR confirmed that ETO-NE is significantly efficacious in mitigating the abundance of IL-B, IL-6, TNF, COX-2, and NF-kB as compared to the free ETO and control group. The current study demonstrates that ETO-NE represents a feasible approach that could provide clinical benefits for lung cancer patients in the future.
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Apoptosis , Emulsiones/química , Etoricoxib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Células A549 , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Movimiento Celular , Proliferación Celular , Etoricoxib/farmacología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatología , Potencial de la Membrana MitocondrialRESUMEN
Febuxostat (FBX) is used to treat gout and chronic hyperuricemia. However, its bioavailability is moderate (49%) as a result of low solubility and first-pass metabolism. Therefore, the aim of our study is to improve FBX bioavailability by enhancement its solubility using self-nanoemulsifying drug delivery system (SNEDDS) technique in the form of transdermal film to avoid hepatic metabolism. To accomplish this goal, Eight SNEDDS formulae were prepared according to a three-factor, two-level D-Optimal mixture design to evaluate the effect of different ratios of the Lemon oil (X1), the surfactant Tween-20 (X2), and the co-surfactant PEG-400 (X3) on the globule size in order to reach smallest globular size. Results revealed that SNEDDS globule size ranged from 177 to 454 nm. The optimized formula consisted of 20% oil, 40% surfactant and 40% co-surfactant. Diffusion study showed improved enhancement in skin permeation that was confirmed by imaging using fluorescence microscope. In vivo plasma data showed significant (p < 0.05) difference in FBX plasma levels and pharmacokinetic parameters when compared with raw FBX loaded film. In conclusion, FBX-SNEDDS loaded transdermal film could be a successful way to improve solubility and skin permeability that would lead to improvement in patient's compliance.
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Sistemas de Liberación de Medicamentos , Febuxostat/administración & dosificación , Supresores de la Gota/administración & dosificación , Nanoestructuras , Administración Cutánea , Animales , Disponibilidad Biológica , Emulsiones , Febuxostat/química , Febuxostat/farmacocinética , Supresores de la Gota/química , Supresores de la Gota/farmacocinética , Masculino , Tamaño de la Partícula , Ratas , Ratas Wistar , Absorción Cutánea , Solubilidad , Tensoactivos/químicaRESUMEN
OBJECTIVE: Adverse events which result from medication errors are considered to be one of the most frequently encountered patient safety issues in clinical settings. We undertook a qualitative investigation to identify and explore factors relating to medication error in an adult oncology department in Saudi Arabia from the perspective of healthcare professionals. METHODS: This was a qualitative study conducted in an adult oncology department in Saudi Arabia. After obtaining required ethical approvals and written consents from the participants, semi-structured interviews and focus group discussions were carried out for data collection. A stratified purposive sampling strategy was used to recruit medical doctors, pharmacists, and nurses. NVivo Pro version 11 was used for data analyses. Inductive thematic analysis was adopted in the primary coding of data while secondary coding of data was carried out deductively applying the Hospital Survey of Patient Safety Culture (HSOPSC) framework. RESULT: The total number of participants were 38. Majority of the participants were nurses (nâ¯=â¯24), females (nâ¯=â¯30), and not of Saudi nationality (nâ¯=â¯31) with an average age of 36â¯years old. Causes of medication errors were categorized into 6 themes. These causes were related teamwork across units, staffing, handover of medication related information, accepted behavioural norms, frequency of events reported, and non-punitive response to error. CONCLUSION: There were numerous causes for medication errors in the adult oncology department. This means substantive improvement in medication safety is likely to require multiple, inter-relating, complex interventions. More research should be conducted to examine context-specific interventions that may have the potential to improve medication safety in this and similar departments.
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OBJECTIVE: There is a wide range of strategies that could help in minimizing medication errors during healthcare delivery. We undertook a qualitative study to identify recommended solutions to minimize medication errors in an adult oncology department in Saudi Arabia from the perspectives of healthcare professionals. METHODS: This was a qualitative study conducted in an adult oncology department in Saudi Arabia. After obtaining the required ethical approvals and written consents from the participants, seven focus group discussions were carried out for data collection. A stratified purposive sampling strategy was used to recruit medical doctors, pharmacists, and nurses. NVivo Pro version 11 was used for data analyses. Inductive content analysis was adopted in the coding of collected data. RESULT: Our study showed that improving organizational support, staff education, and communication could help in minimizing medication errors in the adult oncology department. CONCLUSION: The adoption of multiple strategies is required to improve the safety of the medication process in the adult oncology department. We argue that the availability of supportive leadership should be prioritized as it plays a crucial role in determining the effectiveness and efficiency of both staff education and communication.
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AIMS: A comprehensive description of transcatheter heart valve (THV) failure has not been performed. We undertook a systematic review to investigate the aetiology, diagnosis, management, and outcomes of THV failure. METHODS AND RESULTS: The systematic review was performed in accordance with the PRISMA guidelines using EMBASE, MEDLINE, and Scopus. Between December 2002 and March 2014, 70 publications reported 87 individual cases of transcatheter aortic valve implantation (TAVI) failure. Similar to surgical bioprosthetic heart valve failure, we observed cases of prosthetic valve endocarditis (PVE) (n = 34), structural valve failure (n = 13), and THV thrombosis (n = 15). The microbiological profile of THV PVE was similar to surgical PVE, though one-quarter had satellite mitral valve endocarditis, and surgical intervention was required in 40% (75% survival). Structural valve failure occurred most frequently due to leaflet calcification and was predominantly treated by redo-THV (60%). Transcatheter heart valve thrombosis occurred at a mean 9 ± 7 months post-implantation and was successfully treated by prolonged anticoagulation in three-quarters of cases. Two novel causes of THV failure were identified: late THV embolization (n = 18); and THV compression (n = 7) following cardiopulmonary resuscitation (CPR). These failure modes have not been reported in the surgical literature. Potential risk factors for late THV embolization include low prosthesis implantation, THV undersizing/underexpansion, bicuspid, and non-calcified anatomy. Transcatheter heart valve embolization mandated surgery in 80% of patients. Transcatheter heart valve compression was noted at post-mortem in most cases. CONCLUSION: Transcatheter heart valves are susceptible to failure modes typical to those of surgical bioprostheses and unique to their specific design. Transcatheter heart valve compression and late embolization represent complications previously unreported in the surgical literature.
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Estenosis de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas , Falla de Prótesis/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Embolia/etiología , Endocarditis/tratamiento farmacológico , Endocarditis/etiología , Endocarditis/prevención & control , Femenino , Oclusión de Injerto Vascular/etiología , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
This article suggests a new method to expand a family of life distributions by adding a parameter to the family, increasing its flexibility. It is called the extended Modi-G family of distributions. We derived the general statistical properties of the proposed family. Different methods of estimation were presented to estimate the parameters for the proposed family, such as maximum likelihood, ordinary least square, weighted least square, Anderson Darling, right-tailed Anderson-Darling, Cramér-von Mises, and maximum product of spacing methods. A special sub-model with three parameters called extended Modi exponential distribution was derived along with different shapes of its density and hazard functions. Randomly generated data sets and different estimation methods were used to illustrate the behavior of parameters of the proposal sub-model. To illustrate the importance of the proposed family over the other well-known methods, applications to medicine and geology data sets were analyzed.
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Modelos Estadísticos , Funciones de Verosimilitud , Humanos , AlgoritmosRESUMEN
BACKGROUND: Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. OBJECTIVE: This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. METHODS: The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. RESULTS: The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. CONCLUSION: The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.
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Antineoplásicos , Proliferación Celular , Glioblastoma , Monoterpenos , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Proliferación Celular/efectos de los fármacos , Monoterpenos/farmacología , Monoterpenos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sistemas de Liberación de Medicamentos , Polisorbatos/química , Polisorbatos/farmacología , Composición de Medicamentos , Tamaño de la Partícula , Relación Dosis-Respuesta a Droga , Aceites de Plantas/farmacología , Aceites de Plantas/química , Polietilenglicoles/química , Polietilenglicoles/farmacología , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Células Tumorales CultivadasRESUMEN
Introduction: The extensor pollicis longus (EPL) is a muscle that follows a complex anatomical course in the hand to allow for thumb extension. Almost all manual activities require the use of the EPL; therefore, when ruptured it can be very disabling for patients. The etiologies behind traumatic EPL rupture were mostly attributed to distal radius fracture in the literature. However, EPL rupture remains uncommon, and other traumatic etiologies exist. Therefore, this systematic review aimed to provide a holistic view of the traumatic etiologies behind the EPL rupture and fill the global lack of knowledge regarding this rare injury. Materials and Methods: We searched among Cochrane Central Register of Controlled Trials (CENTRAL) Embase, Medline, and Cochrane Database of systematic review register databases via Ovid, with no restriction on the date, including studies containing data about the etiology of traumatic causes of EPL tendon rupture with available full text, and excluding non-English and animal studies. Results: A total of 37 articles with 371 cases constituted the basis of this review. We classified the etiology of the EPL rupture into three groups according to the affected anatomical structure that caused the EPL rupture (fracture-related, soft tissue-related, and mallet thumb). Conclusion: Distal radius fractures remain the most common cause of EPL rupture; however, other causes, such as lacerations, blunt trauma, and direct cuts to the EPL tendon, should be considered.
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BACKGROUND: There is a paucity of data regarding acute myocardial infarction (MI) complicated by cardiogenic shock (AMI-CS) in the Gulf region. This study addressed this knowledge gap by examining patients experiencing AMI-CS in the Gulf region and analyzing hospital and short-term follow-up mortality. METHODS: The Gulf-CS registry included 1,513 patients with AMI-CS diagnosed between January 2020 and December 2022. RESULTS: The incidence of AMI-CS was 4.1% (1513/37379). The median age was 60 years. The most common presentation was ST-elevation MI (73.83%). In-hospital mortality was 45.5%. Majority of patients were in SCAI stage D and E (68.94%). Factors associated with hospital mortality were previous coronary artery bypass graft (OR:2.49; 95%CI: 1.321-4.693), cerebrovascular accident (OR:1.621, 95%CI: 1.032-2.547), chronic kidney disease (OR:1.572; 95%CI1.158-2.136), non-ST-elevation MI (OR:1.744; 95%CI: 1.058-2.873), cardiac arrest (OR:5.702; 95%CI: 3.640-8.933), SCAI stage D and E (OR:19.146; 95CI%: 9.902-37.017), prolonged QRS (OR:10.012; 95%CI: 1.006-1.019), right ventricular dysfunction (OR:1.679; 95%CI: 1.267-2.226) and ventricular septal rupture (OR:6.008; 95%CI: 2.256-15.998). Forty percent had invasive hemodynamic monitoring, 90.02% underwent revascularization, and 45.80% received mechanical circulatory support (41.31% had Intra-Aortic Balloon Pump and 14.21% had Extracorporeal Membrane Oxygenation/Impella devices). Survival at 12 months was 51.49% (95% CI: 46.44- 56.29%). CONCLUSIONS: The study highlighted the significant burden of AMI-CS in this region, with high in-hospital mortality. The study identified several key risk factors associated with increased hospital mortality. Despite the utilization of invasive hemodynamic monitoring, revascularization, and mechanical circulatory support in a substantial proportion of patients, the 12-month survival rate remained relatively low.
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Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 32-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X1) and varioussuper-disintegrants (X2) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (Tmax), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.
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Nanopartículas , Aceite de Sésamo , Ratas , Animales , Masculino , Valsartán , Disponibilidad Biológica , Ratas Wistar , Emulsiones , Sistemas de Liberación de Medicamentos/métodos , Excipientes , Solubilidad , ComprimidosRESUMEN
Perillyl alcohol (PA), a naturally existing monocyclic terpene related to limonene, is characterized by its poor aqueous solubility and very limited bioavailability. Its potential anti-cancer activity against malignant glioma has been reported. The aim was to develop PA-loaded lipid-based nanocarriers (LNCs), and to investigate their anti-cancer activity against two different brain cell lines. Non-medicated and PA-loaded LNCs were prepared and characterized. The mechanism of cytotoxic activity of PA was conducted using a molecular docking technique. The cell viabilities against A172 and ANGM-CSS cells were evaluated. The results revealed that the average particle size of the prepared LNCs ranged from 248.67 ± 12.42 to 1124.21 ± 12.77 nm, the polydispersity index was 0.418 ± 0.043-0.509 ± 0.064, while the zeta potential ranged from -36.91 ± 1.31 to -15.20 ± 0.96 mV. The molecular docking studies demonstrated that the drug had binding activity to human farnesyltransferase. Following exposure of the two glioblastoma cell lines to the PA-loaded nanoformulations, MTS assays were carried out, and the data showed a far lower half-maximal inhibitory concentration in both cell lines when compared to pure drug and non-medicated nanocarriers. These results indicate the potential in vitro antiproliferative activity of PA-loaded LNCs. Therefore, the prepared PA-loaded nanocarriers could be used to enhance drug delivery across the blood-brain barrier (BBB) in order to treat brain cancer, especially when formulated in a suitable dosage form. The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound's distribution and effects within the brain.
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The use of essential oil-based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil-based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo. In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.
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Candidiasis Bucal , Miel , Nanopartículas , Ratas , Animales , Itraconazol/farmacología , Tensoactivos , Emulsiones , Sistemas de Liberación de Medicamentos/métodos , Solubilidad , Administración Oral , Tamaño de la PartículaRESUMEN
BACKGROUND: Severe mitral regurgitation (MR) with left ventricular dysfunction portends worse outcomes. Over the course of the last two decades, transcatheter repair of the mitral valve offered an alternative therapeutic modality for those deemed inoperable or high risk. Landmark studies such as the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation and Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation trials have shown conflicting results with respect to all-cause death and heart failure rehospitalisations. The Gulf Mitral Transcatheter Edge to Edge Repair registry (Gulf MTEER registry) is a regional registry that captured outcomes in those undergoing transcatheter repair of the mitral valve. The objectives of this study were to describe the baseline characteristics of patients undergoing transcatheter mitral valve repair in the Gulf region and estimate the cardiovascular effects of the mitral transcatheter therapies in routine practice. METHODS: The Gulf MTEER registry is an observational, multicentre, retrospective registry that enrolled all patients undergoing transcatheter repair of the mitral valve from four of the Gulf countries (Saudi Arabia, Kuwait, Bahrain, Oman) between 1 January 2017 and 31 December 2019. Baseline characteristics, echocardiographic parameters and immediate procedural success were reported. The primary outcome was a composite of death and rehospitalisations at 1 year. The secondary outcomes were the individual components of the composite endpoint; that is, death and rehospitalisations at 1 year as well as residual or recurrent MR or worsening New York Heart Association class and a need for repeat repair. RESULTS: A total of 176 patients were enrolled. Men constituted 56.3% of the total. At 1 year the primary outcome occurred in 21.1% (95% CI 15.6, 27.9). The secondary outcomes of death occurred in 5.4% (CI 2.9, 10.0) and rehospitalisations occurred in 16.9% (CI 11.9, 23.3). Univariate analysis revealed that the odds of having death or re-hospitalisation was two times higher if the effective regurgitant orifice (ERO) >40 mm2 irrespective of the therapy. CONCLUSIONS: The Gulf MTEER registry is the first registry in the Gulf region defining the patient population receiving MTEER therapies and evaluating 1-year outcomes. This is a low risk cohort with a high rate of immediate procedural success and low rate of all-cause death and rehospitalisations at 1 year. The odds of an event was two times higher if the ERO ≥40 mm2 with only a signal to higher odds for low left ventricular ejection fraction and larger end systolic dimension.
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Insuficiencia Cardíaca , Insuficiencia de la Válvula Mitral , Masculino , Humanos , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Glimepiride is characterized by an inconsistent dissolution and absorption profile due to its limited aqueous solubility. The aim of this study was to develop glimepiride tablets using three different manufacturing techniques, as well as to study their quality attributes and pharmacokinetics behavior. Black seed oil based self-nanoemulsifying drug delivery system (SNEDDS) formulation was developed and characterized. Glimepiride liquisolid and directly compressed tablets were prepared and their pre-compression and post-compression characteristics were evaluated. Semi-solid pastes loaded with SNEDDS were prepared and used to develop three-dimensional printing tablets utilizing the extrusion technique. In vivo comparative pharmacokinetics study was conducted on Male Wistar rats using a single dose one-period parallel design. The developed SNEDDS formulation showed a particle size of 45.607 ± 4.404 nm, and a glimepiride solubility of 25.002 ± 0.273 mg/mL. All the studied tablet formulations showed acceptable pre-compression and post-compression characteristics and a difference in their in vitro drug release behavior. The surface of the liquisolid and directly compressed tablets was smooth and non-porous, while the three-dimensional printing tablets showed a few porous surfaces. The inner structure of the liquisolid tablets showed some cracks and voids between the incorporated tablet ingredients while that of the three-dimensional printing tablets displayed some tortuosity and a gel porous-like structure. Most of the computed pharmacokinetic parameters improved with the liquisolid and three-dimensional printed tablets. The relative bioavailabilities of the three-dimensional printed and liquisolid tablets compared to commercial product were 121.68% and 113.86%, respectively. Therefore, the liquisolid and three-dimensional printed tablets are promising techniques for modifying glimepiride release and improving in vivo performance but more clinical investigations are required.
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Antiseizure medication have been associated with an increasing risk of congenital anomalies. Medical authorities recommend taking folic acid during the pre-conceptional period to reduce the risk of congenital malformations in the newborns of women with epilepsy (WWE). In this cross-sectional study, we aimed to measure the adherence of Saudi WWE to folic acid intake. We included WWE visiting outpatient epilepsy clinics in King Abdulaziz Medical City and King Fahad Medical City in Riyadh between September 2017 and August 2018. By consecutive non-probability sampling, we identified 85 patients who met the inclusion criteria of the study. The data were collected by a self-administrated questionnaire. We found that the mean age of the subjects was 33 ± 7.5 years. One third were university graduates. Eighty percent were aware of the role of folic acid in preventing congenital anomalies, and 63.9% were taking it during the preconceptional period. No association was found between educational level and adherence to folic acid intake. In conclusion, adherence to folic acid intake among Saudi WWE is not optimal. More efforts are needed to increase patient adherence to folic acid intake.
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BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) is steadily increasing with TAVR procedures offered to patients across the entire spectrum of surgical risks. The Gulf TAVR registry captures the demographics of patients undergoing TAVR in the Gulf region, comorbidities that drive outcomes, procedural success, complications, and one-year outcomes of death or rehospitalization. METHODS: This is a retrospective cohort study for adult patients aged at least 18 years undergoing TAVR at eight centers in the Gulf region. The primary outcome was a composite of death or re-hospitalization at one-year. Secondary outcomes included the individual components of the composite, stroke, and myocardial infarction (MI). We used multivariable Cox regression to determine factors associated with the composite endpoint. RESULTS: A total of 795 patients (56% male) were included in the final analysis with a mean age of 74.6 (standard deviation (SD) 8.9) years, Society of Thoracic Surgeons Score (STS) Score 4.9 (4.2), ejection fraction of 53% (12.7%). Transfemoral approach was employed in over 95% (762/795). The primary outcomes rate was 12.8% (95% confidence interval [CI]: 10.6-15.4); secondary endpoints were death 5.4% (95% CI 4.0-7.2); stroke 0.8% (95% CI 0.3, 1.7), MI 0.8% (95% CI 0.4-1.9), rehospitalization: 9.3% (95% CI 7.5-11.5) of whom 71.6% were related to cardiovascular causes. 77% of the cardiovascular admissions were attributable to heart failure or the need for pacemaker implantation. Stage IV or V chronic kidney disease was significantly associated with the primary composite endpoint (Hazard Ratio: 2.49, [95% CI: 1.31, 4.73], p = 0.005). Although not significant, paravalvular leak and severe left ventricular dysfunction showed a 2-fold and 3-fold increased risk for the composite endpoint, respectively. CONCLUSIONS: The Gulf TAVR registry is the first of its kind in the region. It profiles an elderly population with a high procedural success rate and a low rate of complications. One-year outcomes were primarily driven by repeat hospitalization for heart failure and pacemaker implantation indicating a need to optimize heart failure management and improve algorithms for the detection of conduction abnormalities.
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Estenosis de la Válvula Aórtica , Insuficiencia Cardíaca , Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Adolescente , Adulto , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Masculino , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del TratamientoRESUMEN
Urticaria affects all age groups of a population. It is triggered by allergens in foods, insect bites, medications, and environmental conditions. Urticaria is characterized by itching, a burning sensation, wheals and flares, erythema, and localized edema. The aim of this study was to develop a polymeric dosage form of ebastine using Carbopol 940 and mixture of span and tween. The emulsion was prepared, the gelling agent was added and the desired emulgel loaded with active drug was formulated. The formulations were subjected to physical stability, pH, viscosity, spreadability, drug content analysis, thermal analysis, in vitro drug release, and in vivo anti-allergic activity in animal model. The formulated emulgel exhibited good physical stability. The pH of the formulation was in the range of 5.2 ± 0.17 to 5.5 ± 0.20 which is suitable for topical application. Insignificant changes (p > .05) were observed in viscosity and spreadability of stored emulgels. The drug content was in the official limit of Pharmacopeia (i.e. 100 ± 10%). DSC measurements predicted that there is no interaction between the active moiety and excipients in emulgel formulation. The optimized formulation (ES3) released 74.25 ± 1.8% of ebastine after 12 h. The ebastine emulgel showed significant (p < .05; ANOVA) in vivo anti-allergic activity as compared to commercial product Benadryl® in histamine-induced allergy in rabbits. This study concluded that a topical drug delivery of ebastine-loaded emulgel could be well tolerated and safe for the treatment of urticaria/hives.
Asunto(s)
Resinas Acrílicas/química , Butirofenonas/farmacología , Geles/química , Antagonistas de los Receptores Histamínicos H1/farmacología , Piperidinas/farmacología , Urticaria/patología , Administración Cutánea , Animales , Butirofenonas/administración & dosificación , Química Farmacéutica , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Liberación de Fármacos , Estabilidad de Medicamentos , Emulsiones/química , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Concentración de Iones de Hidrógeno , Masculino , Piperidinas/administración & dosificación , Conejos , Reología , ViscosidadRESUMEN
Flibanserin was licensed by the United States Food and Drug Administration (FDA) as an oral non-hormonal therapy for pre-menopausal women with inhibited sexual desire disorder. However, it suffers from susceptibility to first-pass metabolism in the liver, low aqueous solubility, and degradation in the acidic stomach environment. Such hurdles result in a limited oral bioavailability of 33%. Thus, the aim of the study was to utilize the principles of nanotechnology and the benefits of an intranasal route of administration to develop a formulation that could bypass these drawbacks. A response-surface randomized D-optimal strategy was used for the formulation of flibanserin spanlastics (SPLs) with reduced size and increased absolute zeta potential. Two numerical factors were studied, namely the Span 60: edge activator ratio (w/w) and sonication time (min), in addition to one categorical factor that deals with the type of edge activator. Particle size (nm) and zeta potential (mV) were studied as responses. A mathematical optimization method was implemented for predicting the optimized levels of the variables. The optimized formulation was prepared using a Span: sodium deoxycholate ratio of 8:2 w/w; a sonication time of 5 min showed particle sizes of 129.70 nm and a zeta potential of -33.17 mV. Further in vivo assessment following intranasal administration in rats showed boosted plasma and brain levels, with 2.11- and 2.23-fold increases (respectively) compared to raw FLB. The aforementioned results imply that the proposed spanlastics could be regarded as efficient drug carriers for the trans-nasal delivery of drugs to the brain.
RESUMEN
It is important to create new generations of materials that can destroy multidrug-resistant bacterial strains, which are a serious public health concern. This study focused on the biosynthesis of an essential oil entrapped in titanium dioxide (TiO2) calcium alginate-based microspheres. In this research, calcium alginate-based microspheres with entrapped TiO2 nanoparticles and cinnamon essential oil (CI-TiO2-MSs) were synthesized, using an aqueous extract of Nigella sativa seeds for TiO2 nanoparticle preparation, and the ionotropic gelation method for microsphere preparation. The microspheres obtained were spherical, uniformly sized, microporous, and rough surfaced, and they were fully loaded with cinnamon essential oil and TiO2 nanoparticles. The synthesized microspheres were analyzed for antibacterial activity against the clinical multidrug-resistant strain of Staphylococcus aureus. Disc diffusion and flow cytometry analysis revealed strong antibacterial activity by CI-TiO2-MSs. The synthesized CI-TiO2-MSs were characterized by the SEM/EDX, X-ray diffraction, and FTIR techniques. Results showed that the TiO2 nanoparticles were spherical and 99 to 150 nm in size, whereas the CI-TiO2-MSs were spherical and rough surfaced. Apoptosis analysis and SEM micrography revealed that the CI-TiO2-MSs had strong bactericidal activity against S. aureus. The in vitro antibacterial experiments proved that the encapsulated CI-TiO2-MSs had strong potential for use as a prolonged controlled release system against multidrug-resistant clinical S. aureus.