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BACKGROUND: This study evaluated the pharmacokinetic interactions of orally administered chloroquine and metoclopramide. METHODS: The study employed a randomized and two-phase cross-over design with 4-week washout plan. Twelve healthy male volunteers were shortlisted according to the set criteria and were administered with metoclopramide 10 mg PO and chloroquine (a total of 1500 mg) at different intervals which were (500 mg at 0, 6, and 24 h). The concentration of chloroquine and metoclopramide in the blood samples was estimated using a validated HPLC-UV technique to affirm the maximum concentration (Cmax), time to reach Cmax (Tmax), and area under the curve (AUC). RESULTS: Cmax, T1/2, and AUC of metoclopramide were increased up to 20, 10, and 47.8%, respectively, by the concomitantly administering Chloroquine. Chloroquine-treated phase showed increased values of Cmax (ng/ml), AUC (ng.h/ml), and T½ (h), i.e. 41.35 ± 1.61, 504.12 ± 66.25, and 5.72 ± 2.63, as compared to that reference phase i.e. 34.52 ± 4.92, 341.14 ± 112.8, and 5.19 ± 1.14, respectively. CONCLUSIONS: Chloroquine was found to attenuate CYP2D6 activity in healthy Pakistani male volunteers. Hence, patients that are prescribed with metoclopramide or other CYP2D6-substrate drugs require a dose adjustment when administered with chloroquine.
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BACKGROUND: Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. OBJECTIVE: This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. METHODS: MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. RESULTS: Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. CONCLUSION: Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.
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Neoplasias de la Mama , Glucosamina , Ratones , Humanos , Animales , Femenino , Acetilglucosamina/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Simulación del Acoplamiento Molecular , Modelos Animales de EnfermedadRESUMEN
This research study was designed with the aim to prepare plant extract-mediated iron oxide nanoparticles (IONPs) and different chemically modified carbon adsorbents from the Parthenium hysterophorus plant and then optimize the carbon adsorbents by evaluating their adsorption applications in wastewater for the selected metal ions like arsenic (As3+), lead (Pb2+), and cadmium (Cd2+). The Fourier transform infrared spectroscopy (FTIR) technique was used to highlight functional groups in plant-mediated IONPs and chemically modified carbon adsorbents. A scanning electron microscopy study was conducted to explain the surface morphology of the adsorbents. Energy-dispersive X-rays was used for elemental analysis and X-ray diffraction for particle size and crystallinity of the adsorbents. From the study, it was found that the best optimum conditions were pH = 5-6, initial concentration of adsorbate of 10 mg/L, dose of adsorbent of 0.01 g, contact time of 90-120 min of adsorbent and adsorbate, and temperature of 25 °C. At optimum conditions, the adsorption capacities of IONPs for arsenic (As) 144.7 mg/g, lead (Pb) 128.01 mg/g, and cadmium (Cd) ions 122.1 mg/g were recorded. The activated carbon at optimum conditions showed adsorption capacities of 46.35 mg/g for As, 121.95 mg/g for Pb, and 113.25 mg/g for Cd ion. At equilibrium, Langmuir, Freundlich Temkin, and Dubinin-Radushkevich isotherms were applied on the experimental adsorption data having the best R2 values (0.973-0.999) by the Langmuir isotherm. High-correlation coefficient R2 values (0.996-0.999) were obtained from the pseudo-second-order for all cases, showing that the adsorption process proceeds through pseudo second-order kinetics. The apparent adsorption energy E value was in the range of 0.24-2.36 kJ/mol. The adsorption capacity of regenerated IONPs for As gradually decreased from 144.8 to 45.67 mg/g, for lead 128.15 to 41.65 mg/g, and cadmium from 122.10 to 31.20 mg/g in 5 consecutive cycles. The study showed that the synthesized IONPs and acid-activated carbon adsorbent were successfully used to remove selected metal ions from wastewater.
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Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aß) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.
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Enfermedad de Alzheimer , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Ratas , Animales , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Inflamasomas , Péptidos beta-Amiloides/farmacología , Enfermedades Neuroinflamatorias , Sulfonamidas/farmacología , Cognición , Autofagia , Peso CorporalRESUMEN
Cancer remains a major cause of morbidity and mortality worldwide, and while current therapies, such as chemotherapy, immunotherapy, and cell therapy, have been effective in many patients, the development of novel therapeutic options remains an urgent priority. Mouse double minute 2 (MDM2) is a key regulator of the tumor suppressor protein p53, which plays a critical role in regulating cellular growth, apoptosis, and DNA repair. Consequently, MDM2 has been the subject of extensive research aimed at developing novel cancer therapies. In this study, we employed a machine learning-based approach to establish a quantitative structure-activity relationship model capable of predicting the potential in vitro efficacy of small molecules as MDM2 inhibitors. Our model was used to screen 5883 FDA-approved drugs, resulting in the identification of promising hits that were subsequently evaluated using molecular docking and molecular dynamics simulations. Two antihistamine drugs, cetirizine (CZ) and rupatadine (RP), exhibited particularly favorable results in the initial in silico analyses. To further assess their potential use as the activators of the p53 pathway, we investigated the antiproliferative capability of the abovementioned drugs on human glioblastoma and neuroblastoma cell lines. Both the compounds exhibited significant antiproliferative effects on the abovementioned cell lines in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) of CZ was found to be 697.87 and 941.37 µM on U87 and SH-SY5Y cell lines, respectively, while the IC50 of RP was found to be 524.28 and 617.07 µM on the same cell lines, respectively. Further investigation by quantitative reverse transcriptase polymerase chain reaction analysis revealed that the CZ-treated cell lines upregulate the expression of the p53-regulated genes involved in cell cycle arrest, apoptosis, and DNA damage response compared to their respective vehicle controls. These findings suggest that CZ activates the p53 pathway by inhibiting MDM2. Our results provide compelling preclinical evidence supporting the potential use of CZ as a modulator of the MDM2-p53 axis and its plausible repurposing for cancer treatment.
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HIV-1 is a deadly virus that affects millions of people worldwide. In this study, we aimed to inhibit viral replication by targeting one of the HIV-1 proteins and identifying a new drug candidate. We used data mining and molecular dynamics methods on HIV-1 genomes. Based on MAUVE analysis, we selected the RNase H activity of the reverse transcriptase (R.T) enzyme as a potential target due to its low mutation rate and high conservation level. We screened about 94,000 small molecule inhibitors by virtual screening. We validated the hit compounds' stability and binding free energy through molecular dynamics simulations and MM/PBSA. Phomoarcherin B, known for its anticancer properties, emerged as the best candidate and showed potential as an HIV-1 reverse transcriptase RNase H activity inhibitor. This study presents a new target and drug candidate for HIV-1 treatment. However, in vitro and in vivo tests are required. Also, the effect of RNase H activity on viral replication and the interaction of Phomoarcherin B with other HIV-1 proteins should be investigated.
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Herein, a novel and environmentally benign solid catalyst was fabricated by grafting WO3 active species onto the ZnCo2O4@CeO2 support for efficient levulinic acid production from corncob waste biomass. The morphological, compositional, and textural properties of the designed catalyst were investigated using different characterization techniques to identify suitable catalyst formulation with enhanced catalytic activity and stability. The results demonstrated that WO3 active species were successfully loaded with uniform distribution onto the support to develop a robust catalyst with both acidic and basic sites. The experimental investigation showed that among the catalysts, WO3(10 wt %)/ZnCo2O4@CeO2 exhibited the best catalytic activity, providing a maximum levulinic acid yield of 78.49% at the optimal conditions of 6 wt % catalyst dosage, reaction temperature of 180 °C, and reaction time of 200 min. The presence of an optimum number of both acid and base active sites on the catalyst surface could lead to the highest catalytic activity of the synthesized catalyst. Finally, the reusability investigation indicated that the synthesized catalyst possessed sufficient recyclability of up to four times for the levulinic acid production from the selected biomass with negligible drop in the catalytic activity.
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Binary composite of zerovalent iron and titanium dioxide (Fe0/TiO2) was synthesized for the catalytic removal of dichlorophene (DCP) in the presence of peroxymonosulfate (PMS). The as-prepared composite (Fe0/TiO2) exhibits synergistic effect and enhanced properties like improved catalytic activity of catalyst and greater magnetic property for facile recycling of catalyst. The results showed that without addition of PMS at reaction time of 50 min, the percent degradation of DCP by TiO2, Fe0, and Fe0/TiO2 was just 5%, 11%, and 12%, respectively. However, with the addition of 0.8 mM PMS, at 10 min of reaction time, the catalytic degradation performance of Fe0, TiO2, and Fe0/TiO2 was significantly improved to 82%, 18%, and 88%, respectively. The as-prepared catalyst was fully characterized to evaluate its structure, chemical states, and morphology. Scanning electron microscopy results showed that in composite TiO2 causes dispersion of agglomerated iron particles which enhances porosity and surface area of the composites and X-ray diffraction (XRD), energy dispersive X-ray (EDX), and Fourier-transform infrared (FTIR) results revealed successful incorporation of Fe0, and oxides of Fe and TiO2 in the composite. The adsorption-desorption analysis verifies that the surface area of Fe0/TiO2 is significantly larger than bare Fe0 and TiO2. Moreover, the surface area, particle size, and crystal size of Fe0/TiO2 was surface area = 85 m2 g-1, particle size = 0.35 µm, and crystal size = 0.16 nm as compared to TiO2 alone (surface area = 22 m2 g-1, particle size = 4.25 µm, and crystal size = 25.4 nm) and Fe0 alone (surface area = 65 m2 g-1, particle size = 0.9 µm, and crystal size = 7.87 nm). The as-synthesized material showed excellent degradation performance in synthesized wastewater as well. The degradation products and their toxicities were evaluated and the resulted degradation mechanism was proposed accordingly. The toxicity values decreased in order of DP1 > DP5 > DP2 > DP3 > DP4 and the LC50 values toward fish for 96-h duration decreased from 0.531 to 67.2. This suggests that the proposed technology is an excellent option for the treatment of antibiotic containing wastewater.
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Diclorofeno , Hierro , Animales , Antibacterianos , Catálisis , Hierro/química , Estrés Oxidativo , Peróxidos , Titanio/química , Aguas Residuales , AguaRESUMEN
Stem cell therapies have emerged as a promising treatment strategy for various diseases characterized by ischemic injury such as ischemic stroke. Cell survival after transplantation remains a critical issue. We investigated the impact of oxidative stress, being typically present in ischemically challenged tissue, on human dental pulp stem cells (hDPSC) and human mesenchymal stem cells (hMSC). We used oxygen-glucose deprivation (OGD) to induce oxidative stress in hDPSC and hMSC. OGD-induced generation of O2â¢- or H2O2 enhanced autophagy by inducing the expression of activating molecule in BECN1-regulated autophagy protein 1 (Ambra1) and Beclin1 in both cell types. However, hDPSC and hMSC pre-conditioning using reactive oxygen species (ROS) scavengers significantly repressed the expression of Ambra1 and Beclin1 and inactivated autophagy. O2â¢- or H2O2 acted upstream of autophagy, and the mechanism was unidirectional. Furthermore, our findings revealed ROS-p38-Erk1/2 involvement. Pre-treatment with selective inhibitors of p38 and Erk1/2 pathways (SB202190 and PD98059) reversed OGD effects on the expression of Ambra1 and Beclin1, suggesting that these pathways induced oxidative stress-mediated autophagy. SIRT3 depletion was found to be associated with increased oxidative stress and activation of p38 and Erk1/2 MAPKs pathways. Global ROS inhibition by NAC or a combination of polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-catalase) further confirmed that O2â¢- or H2O2 or a combination of both impacts stems cell viability by inducing autophagy. Furthermore, autophagy inhibition by 3-methyladenine (3-MA) significantly improved hDPSC viability. These findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may deduce strategies to minimize therapeutic cell loss under oxidative stress.
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Autofagia , Peróxido de Hidrógeno , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis , Beclina-1/metabolismo , Beclina-1/farmacología , Supervivencia Celular , Glucosa/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , Oxígeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células Madre/metabolismoRESUMEN
The designing and preparing of low-cost and easily available electrocatalyst for oxygen evolution reaction (OER) are crucial for many advanced energy technologies. Herein, the Ni3S2 nanostrips@FeNi-NiFe2O4 nanoparticles embedded in N-doped carbon (Ni3S2@FeNi-NiFe2O4/C) microspheres were synthesized as improved electrocatalyst for OER, using a facile heat-treatment method. The optimized Ni3S2@FeNi-NiFe2O4/C-3 sample exhibits enhanced electrocatalytic activity toward OER performance with an overpotential of 280 mV at 10 mA cm-2 and a small Tafel slope of 33.9 mV dec-1. Furthermore, Ni3S2@FeNi-NiFe2O4/C-3 composite shows good stability in alkaline media. The outstanding electrocatalytic OER performance of composites was attributed due to the synergetic effect between Ni3S2 nanostrips and FeNi-NiFe2O4 nanoparticles and it is believed that the heterointerfaces between them act as active centers for OER. Additionally, N-doped carbon prevents the aggregation of Ni3S2@FeNi-NiFe2O4 species and enhances the conductivity of composites during the OER process.
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The iron metal-organic framework composite with chitosan (CS/MOF-235) was synthesized using a solvothermal method and its synthesis was confirmed by surface area, PZC, XRD, FESEM, XPS, TGA, TEM, EDX mapping and EDX analysis. The chitosan composite of the iron metal-organic framework (CS/MOF-235), MOF-235 and chitosan were used for the removal of methylene blue (MB) and methyl orange (MO) from aqueous solutions. The maximum adsorption capacities were found to be 2857-2326 mg/g for CS/MOF-235, 357 - 236 mg/g for MOF-235 and 209-171 mg/g for chitosan (CS) which reveal that the adsorption capacity of CS/MOF-235 is almost 8 and 14 times greater than MOF-235 and chitosan respectively. The adsorption selectivity of the (CS/MOF-235) towards the dye was in the order MO > MB. Moreover, hydrogen bonding, pi-pi bonding, pore-filling, electrostatic interactions and chemisorption were proposed as possible mechanisms for the removal of dyes onto CS/MOF-235. The intraparticle diffusion and Richenberg models confirmed that the adsorption process was jointly controlled by the pore and film diffusion. The negative values of the isosteric heat of adsorption (ΔH¯) fall with surface coverage indicating that a lesser amount of heat is required for the greater uptake of dyes.
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Quitosano , Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Adsorción , Colorantes , Concentración de Iones de Hidrógeno , Cinética , Termodinámica , Contaminantes Químicos del Agua/análisisRESUMEN
The novel Na-SiO2@TiO2 heterogeneous base catalyst was designed and successfully applied to the trans-esterification reaction of waste cooking oil for sustainable biodiesel production. The designed catalyst was characterized by SEM, XPS, FT-IR and BET before treatment, illustrated its suitability for the catalytic trans-esterification reaction. Moreover, the influence of reaction temperature, time, catalyst concentration and WCO:MeOH molar ratio on the catalytic activity were also investigated, resultant 98% biodiesel yield was achieved. The reusability test demonstrated that the Na-SiO2@TiO2 catalyst has noticeable catalytic potency up to 5 successive runs. Besides, the kinetics study explains that the reaction is kinetically controlled by pseudo 1st order. The Ea was found to be 21.65 kJ/mol. Similarly, the important thermodynamic parameters such as ΔH#, ΔS# and ΔG# were estimated to be 18.52 kJ.mol-1, -219.17 J.mol-1K-1and 92.59 kJ.mol-1respectively.
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Biocombustibles , Dióxido de Silicio , Biocombustibles/análisis , Catálisis , Culinaria , Esterificación , Cinética , Aceites de Plantas , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Mucus is an integral part of the respiratory physiology. It protects the respiratory tract by acting as a physical barrier against inhaled particles and microbes. Excessive inflammation in conditions such as COVID-19 can result in over-production of mucus which obstructs the airway. Build-up of mucus can also contribute to recurrent airway infection, causing further obstruction. This article summarizes the current understanding and knowledge of respiratory mucus production and proposes the role of cytokine storm in inducing sudden mucus hypersecretion in COVID-19. Based on these cascades, the active constituents that inhibit or activate several potential targets are outlined for further research. These may be explored for the discovery and design of drugs to combat cytokine storm and its ensuing complications.
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This paper comprises a comprehensive kinetic study for the adsorptive removal of As (V) from aqueous medium by mixed oxide (MO) of iron and silicon. The multi-linearity of the intraparticle diffusion model pointed towards the likelihood of both the pore and film diffusion. The Boyd model validated film diffusion to be the principal mechanism responsible for controlling the rate of the arsenate adsorption on MO. The negative entropy of activation (ΔS#) suggested the adsorption mechanism to be associative in nature. The non-negative values of ΔG# suggested the presence of an energy barrier to be surmounted for the reaction to occur.
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Arseniatos , Hierro , Adsorción , Cinética , Óxidos , SilicioRESUMEN
OBJECTIVES: The authors describe a case of congenital calvarial hemangioma successfully managed using propranolol therapy. Presenting symptoms, radiological and pathological features, differential diagnosis, and management of this rare congenital mass are described. CASE PRESENTATION: A 2-year-old boy presented with a 1-year history of a growing right parietal skull mass. No obvious etiology was apparent. No focal neurological deficits or associated craniofacial anomalies were identified. Plain film imaging demonstrated focal thickening of the right parietal bone with internal trabeculations in a sunburst appearance. Computed tomography (CT) scan showed bone thickening with coarsening of the bony trabeculae, minor irregularity of the outer table, unaffected inner table, and no evidence of aggressive features. A diagnostic biopsy of the lesion was performed in the operating room. Microscopic examination was consistent with hemangioma. Based on histological and radiological features of the lesion, it was identified as a cavernous hemangioma. Medical treatment utilizing propranolol was initiated for over 3 years with interval reduction in the lesion size. MRI head following treatment with propranolol demonstrated reduction of the mass compared to preoperative imaging. CONCLUSIONS: Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma's intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations.
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Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/tratamiento farmacológico , Propranolol/uso terapéutico , Neoplasias Craneales/diagnóstico , Neoplasias Craneales/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Preescolar , Hemangioma Cavernoso/congénito , Humanos , Masculino , Hueso Parietal , Neoplasias Craneales/congénitoRESUMEN
High surface area mesoporous activated carbon-alginate (AC-alginate) beads were successfully synthesized by entrapping activated carbon powder derived from Mangosteen fruit peel into calcium-alginate beads for methylene blue (MB) removal from aqueous solution. The structure and surface characteristics of AC-alginate beads were analyzed using Fourier transform infra-red (FTIR) spectroscopy, scanning electron microscopy (SEM) and surface area analysis (SBET), while thermal properties were tested using thermogravimetric analysis (TGA). The effect of AC-alginate dose, pH of solution, contact time, initial concentration of MB solution and temperature on MB removal was elucidated. The results showed that the maximum adsorption capacity of 230mg/g was achieved for 100mg/L of MB solution at pH 9.5 and temperature 25°C. Furthermore, the adsorption of MB on AC-alginate beads followed well pseudo-second order equation and equilibrium adsorption data were better fitted by the Freundlich isotherm model. The findings reveal the feasibility of AC-alginate beads composite to be used as a potential and low cost adsorbent for removal of cationic dyes.
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Alginatos/química , Carbón Orgánico/química , Azul de Metileno/química , Adsorción , Técnicas de Cultivo Celular por Lotes , Colorantes/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Cinética , Nitrógeno/química , Porosidad , Soluciones , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Termodinámica , Termogravimetría , Factores de TiempoRESUMEN
BACKGROUND: Carotid stent fractures are rare, and multiple etiologies have been proposed to explain their occurrence. We describe a patient with an internal carotid artery (ICA) stent who developed in-stent restenosis. We performed balloon angioplasty to address in-stent restenosis, but he developed a carotid stent fracture after the procedure. To our knowledge, balloon angioplasty has not been reported to cause stent fractures. CASE DESCRIPTION: A 72-year-old man underwent stent placement for symptomatic left ICA stenosis with residual stenosis of 55% after stent placement. He presented with transient ischemic attacks 2 months later, and work-up revealed in-stent restenosis of the left ICA. Given prior complete occlusion of right ICA and right vertebral artery and narrowing of left vertebral artery ostium, satisfactory balloon (5 × 40 mm) angioplasty was carried out. After balloon angioplasty, x-ray showed a new stent fracture, which was initially missed on immediate postoperative imaging. He presented 9 months later with symptoms of compromised cerebral perfusion. Work-up revealed the previously missed stent fracture causing blood flow changes. Peak systolic velocity in the left ICA was 383 cm/second. He underwent left ICA repeat stent placement via a stent-in-stent technique for symptomatic severe left ICA stenosis of 70% with 40% residual stenosis after new stent deployment. CONCLUSIONS: Balloon angioplasty to address in-stent restenosis can secondarily cause stent fractures. We provide evidence of successful management of stent fracture with recurrent in-stent stenosis by repeat stent placement via a stent-in-stent technique.
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Angioplastia de Balón/métodos , Arteria Carótida Interna/diagnóstico por imagen , Oclusión de Injerto Vascular/diagnóstico por imagen , Falla de Prótesis/efectos adversos , Stents/efectos adversos , Anciano , Oclusión de Injerto Vascular/etiología , Humanos , MasculinoRESUMEN
BACKGROUND: Randomized controlled trials (RCTs) form the foundational background of modern medical practice. They are considered the highest quality of evidence, and their results help inform decisions concerning drug development and use, preventive therapies, and screening programs. However, the inputs that justify an RCT to be conducted have not been studied. METHODS: We reviewed the MEDLINE and EMBASE databases across six specialties (Ophthalmology, Otorhinolaryngology (ENT), General Surgery, Psychiatry, Obstetrics-Gynecology (OB-GYN), and Internal Medicine) and randomly chose 25 RCTs from each specialty except for Otorhinolaryngology (20 studies) and Internal Medicine (28 studies). For each RCT, we recorded information relating to the justification for conducting RCTs such as average study size cited, number of studies cited, and types of studies cited. The justification varied widely both within and between specialties. RESULTS: For Ophthalmology and OB-GYN, the average study sizes cited were around 1100 patients, whereas they were around 500 patients for Psychiatry and General Surgery. Between specialties, the average number of studies cited ranged from around 4.5 for ENT to around 10 for Ophthalmology, but the standard deviations were large, indicating that there was even more discrepancy within each specialty. When standardizing by the sample size of the RCT, some of the discrepancies between and within specialties can be explained, but not all. On average, Ophthalmology papers cited review articles the most (2.96 studies per RCT) compared to less than 1.5 studies per RCT for all other specialties. CONCLUSIONS: The justifications for RCTs vary widely both within and between specialties, and the justification for conducting RCTs is not standardized.