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1.
Nano Lett ; 23(21): 9690-9696, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37884274

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial, venous, and microvascular thrombosis where activated neutrophils play a determinant role. However, neutrophils are challenging to target given their short lifespan in circulation and spontaneous activation. Screening of a small library of gold nanoparticles (AuNPs) led to the discovery of a formulation capable of targeting activated neutrophil attachment and has demonstrated that star-shaped, anti-PSGL-1-antibody-coated AuNPs (aPSGL-1-AuNPs) were more efficacious compared with other shapes of AuNPs. Our findings further revealed an exciting and safe targeting mode toward activated neutrophils in the APS mouse model induced by human-patient-derived antiphospholipid IgGs. Our studies demonstrate that targeting is dependent on the specific topographical features of the highly segregated PSGL-1 on the activated neutrophil surface for which a high affinity shape-driven nanomedicine can be designed and implemented. As such, star-shaped aPSGL-1-AuNPs serve as a promising nanoimmunotherapy for immunothrombosis associated with neutrophil adhesion in APS.


Asunto(s)
Síndrome Antifosfolípido , Nanopartículas del Metal , Trombosis , Animales , Ratones , Humanos , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Neutrófilos , Oro/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Trombosis/tratamiento farmacológico , Inmunoglobulina G
2.
J Chem Phys ; 159(24)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38156635

RESUMEN

We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications.

3.
Phytother Res ; 35(9): 4763-4781, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33908677

RESUMEN

Global diabetes epidemic is the major cause of fatality and lethality. As per IDF 2019 report, diabetes caused 4.2 million deaths, approximately 463 million people are living with diabetes and by 2045, this will rise to 700 million. Nowadays, the physicians and common people in both developed and developing countries are using medicinal plants and their formulations to treat diseases with the postulation that organic commodities are safe for consumption. These plants may act as inhibitors or inducers of the Cytochrome P450 or transport and efflux proteins or both and may alter gastrointestinal, renal functions leading to Herb-Drug Interactions. This review intends to focus on the frequently employed medicinal plants, their traditional uses, their Cytochrome P450 inhibition or induction activity, phytochemical, and pharmacological effects, established HDI with the help of in vitro tools, in vivo pharmacokinetics and pharmacodynamics studies to understand the impact of herbs on ADME of the drug and whether it is beneficial, harmful or has no effect respectively. This review will help the physicians and other health care professionals as a reference guide to update their knowledge and expertise about HDI. However, more quality research in this area is needed to evaluate the efficacy of many herbal medicines, thereby reducing side effects and improving the safety of patients.


Asunto(s)
Diabetes Mellitus , Interacciones de Hierba-Droga , Plantas Medicinales , Transporte Biológico , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Humanos , Plantas Medicinales/efectos adversos
4.
Phytother Res ; 34(5): 1008-1026, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31908085

RESUMEN

About 70% of the world population is currently using medicinal herbs as complementary or alternative medicine, which is increasing at a tremendous pace in both developed and developing countries in the last two decades (World Health Organization Medicines Strategy 2002-2005). This increase in consumer demand of medicinal herbs continues despite the rarity of scientific data to establish their safety and efficacy profile. Its popularity is also attributed to several factors, including easy availability, cost effectiveness leading to better purchasing power and general perception that they are safe. Herbs are often administered concomitantly with therapeutic drugs for the treatment of major ailments, raising the potential for herb-drug interactions (HDIs). The major pathways postulated for HDIs involves the cytochrome P450 (CYP450)-mediated inhibition or induction and transport and efflux proteins. In our review, we highlight frequently used herbal medicines for the treatment of cardiovascular disorders (CVD), their established HDIs studied using in vitro tools and in vivo pharmacokinetic and pharmacodynamic assays and case reports. Herbs have been divided into different sections on the basis of availability of HDI data in relevance to cardiovascular drugs: herbs reported to interact with cardiac drugs, herbs yet to be reported for interaction with drugs of any class and herbs reported to interact with drugs of other therapeutic category but not with cardiac drugs. The amount of active phytoconstituents present in the selected herbs and their extent of bioavailability are also mentioned. This review can serve as a quick reference database for physicians and health care professionals involved in CVD treatment, aimed at maximizing clinical outcomes with reduction in adverse and toxic effects.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Interacciones de Hierba-Droga/fisiología , Plantas Medicinales/química , Humanos
5.
Indian J Med Res ; 142(5): 525-32, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26658585

RESUMEN

BACKGROUND & OBJECTIVES: Persistent infections with high-risk (HR) human papillomaviruses such as HPV 16, 18, 31, 33 and 45 have been identified as the major aetiological factor for cervical cancer. The clinical outcome of the disease is often determined by viral factors such as viral load, physical status and oncogene expression. The aim of the present study was to evaluate the impact of such factors on clinical outcome in HPV16 positive, locally advanced cervical cancer cases. METHODS: One hundred and thirty two pretreatment cervical tumour biopsies were selected from patients undergoing radiotherapy alone (n=63) or concomitant chemo-radiation (n=69). All the samples were positive for HPV 16. Quantitative real time-PCR was carried out to determine viral load and oncogene expression. Physical status of the virus was determined for all the samples by the ratio of E2 copies /E7 copies ; while in 73 cases, the status was reanalyzed by more sensitive APOT (amplification of papillomavirus oncogene transcripts) assay. Univariate analysis of recurrence free survival was carried out using Kaplan-Meier method and for multivariate analysis the Cox proportional hazard model was used. RESULTS: The median viral load was 19.4 (IQR, 1.9- 69.3), with viral integration observed in 86 per cent cases by combination of the two methodologies. Both univariate and multivariate analyses identified viral physical status as a good predictor of clinical outcome following radiation treatment, with episomal form being associated with increased recurrence free survival. INTERPRETATION & CONCLUSIONS: The present study results showed that viral physical status might act as an important prognostic factor in cervical cancer.


Asunto(s)
Alphapapillomavirus/genética , Biomarcadores de Tumor/análisis , Genes Virales , Mutagénesis Insercional , Neoplasias del Cuello Uterino/virología , Femenino , Humanos , Estudios Retrospectivos
6.
In Silico Pharmacol ; 12(1): 19, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550524

RESUMEN

Chronic wound healing, especially in burns, is a major medical challenge with limited treatments. This study employs computational tools to identify phytomolecules that target multiple pathways involved in wound healing. By utilizing shape analysis, molecular docking, and binding energy calculations, potential compounds are pinpointed,to address the growing problem of chronic wounds. Initially, a set of phytomolecules from the ZINC database of natural molecules was screened to find compounds with shapes similar to well-known wound healing phytomolecules like curcumin, chromogenic acid, gallic acid, and quercetin. The most promising phytomolecules identified through shape similarity were further studied through molecular docking studies on several key targets involved in wound healing, including TNF-α, FGF, and TGF-ß. Among the tested phytomolecules, a ligand known as Fluorophenyl(5-(5-chloro-1-(2-fluorophenyl)-2-oxopentyl)-4,5,6,7-tetrahydrothieno[3,2c]pyridine-2-yl acetate) exhibited a strong affinity with favourable binding interactions for TNF-α ( - 7.1 kcal/mole), FGF (-6.9 kcal/mole), and TGF-ß (-5.1 kcal/mole). Another compound, 2,4 methoxybenzylidene-(-3)-oxo-2,3-dihydro-1-benzofuran-6-yl-4-methoxybenzoate, demonstrated a strong affinity with low binding energy for TNF-α ( - 6.8 kcal/mole) and FGF ( - 7.0 kcal/mole) targets. Isosakuranetin and Ermanin displayed moderate affinity for both TNF-α and FGF, with the highest affinity observed for the TGF-ß target. These findings suggest that these identified phytomolecules hold promise as potential lead compounds for further structural modifications, with the goal of designing new molecules that can target multiple pathways involved in the wound healing process.

7.
Curr Diabetes Rev ; 19(4): e010422202937, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35366781

RESUMEN

Wound management is one of the major global challenges in recent times, and woundassociated infection has a significant impact on the healthcare economy worldwide. Wounds can be acute or chronic type, also diabetic, trauma, accidental, burn wounds and minor cuts, bruises, and rashes, etc. One of the primary treatment options available in these conditions are the use of suitable dressing materials to cover the wound and accelerate the healing process. Since ancient times, according to archaeological theories, medicinal plants and oils have been employed for the treatment of wounds. Today researchers across the globe are focusing their efforts on fabrication of novel dressing materials that can provide the most effective treatment, easy exchange of nutrients, and absorb exudate from the wounds. Very lately, various research groups are also concentrating on the design and development of herb-loaded wound dressings, as herbal preparations contain numerous phytoconstituents with a broad spectrum of pharmacological properties when compared to synthetic drugs and also due to the perceived notion that herbal products are generally safe, even when administered over prolonged periods. They contain numerous bioactive that can act on the various phases of the wound healing process, providing an ideal environment for the healing process. The present review discusses the numerous approaches that are employed for the preparation of dressing materials incorporated with plant-derived phytoconstituents/extracts. This review also provides an insight into the healing process and wound healing agents derived from medicinal plants and oils. The review can serve as a database for researchers working in this field and can help them to select the most appropriate dressing material for the effective delivery of herbal preparations in the management of wounds.


Asunto(s)
Vendajes , Cicatrización de Heridas , Humanos , Resultado del Tratamiento , Exudados y Transudados , Preparaciones de Plantas/uso terapéutico
8.
Eur J Gastroenterol Hepatol ; 35(12): 1324-1333, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37823422

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial complicated condition, reflected by the accumulation of extra fat in the liver. A detailed study of literature throws light on the fascinating connection between gut dysbiosis and NAFLD. The term 'gut dysbiosis' describes an imbalance in the harmony and operation of the gut microflora, which can upshoot a number of metabolic disorders. To recognize the underlying mechanisms and determine treatment options, it is essential to comprehend the connection between gut dysbiosis and NAFLD. This in-depth review discusses the normal gut microflora composition and its role in health, alterations in the gut microflora composition that leads to disease state focusing on NAFLD. The potential mechanisms influencing the advent and aggravation of NAFLD suggested disturbance of microbial metabolites, changes in gut barrier integrity, and imbalances in the composition of the gut microflora. Furthermore, it was discovered that gut dysbiosis affected immune responses, liver inflammation, and metabolic pathways, aggravating NAFLD.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Disbiosis , Hígado/metabolismo
9.
J Relig Health ; 51(1): 20-31, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22069057

RESUMEN

Measures of religiosity are linked to health outcomes, possibly indicating mediating effects of associated psychological and social factors. We examined cross-sectional data from 92,539 postmenopausal participants of the Women's Health Initiative Observational Study who responded to questions on religious service attendance, psychological characteristics, and social support domains. We present odds ratios from multiple logistic regressions controlling for covariates. Women attending services weekly during the past month, compared with those not attending at all in the past month, were less likely to be depressed [OR = 0.78; CI = 0.74-0.83] or characterized by cynical hostility [OR = 0.94; CI = 0.90-0.98], and more likely to be optimistic [OR = 1.22; CI = 1.17-1.26]. They were also more likely to report overall positive social support [OR = 1.28; CI = 1.24-1.33], as well as social support of four subtypes (emotional/informational support, affection support, tangible support, and positive social interaction), and were less likely to report social strain [OR = 0.91; CI = 0.88-0.94]. However, those attending more or less than weekly were not less likely to be characterized by cynical hostility, nor were they less likely to report social strain, compared to those not attending during the past month.


Asunto(s)
Pacientes/psicología , Religión y Psicología , Apoyo Social , Salud de la Mujer , Anciano , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Encuestas y Cuestionarios , Estados Unidos
10.
Artículo en Inglés | MEDLINE | ID: mdl-35711860

RESUMEN

Introduction: Teriparatide, recombinant human parathyroid hormone (1-34), is a safe and usually well-tolerated medication. We describe two cases of late-onset hypercalcemia associated with teriparatide use and report current evidence of hypercalcemia during the treatment with PTH analogs. Case report: Case 1 is a 54-year-old man with a history of osteoporosis, previously treated with 6 months of teriparatide, but had not been consistent in taking the medication. Before restarting teriparatide, his serum calcium, PTH and vitamin D were normal. Six months into the treatment, he developed asymptomatic hypercalcemia of 11.2 mg/dL 24 h after the last dose. Repeat serum calcium was normal and treatment was continued. Case 2 is a 75-year old woman with a history of osteopenia and severe scoliosis. Before starting teriparatide, her calcium, PTH and vitamin D were normal. Six months into the treatment, she developed asymptomatic hypercalcemia of 12.5 mg/dL. Teriparatide was held and subsequently her serum calcium normalized. Discussion: Transient hypercalcemia can occur during treatment with teriparatide and usually resolves within 16 h after administration. Late hypercalcemia, occurring more than 24 h after the dose, is rarely seen. It is usually mild, asymptomatic and rarely occurs repeatedly. Hypercalcemia occurs more often in patients with pre-existing hypercalcemia or vitamin D deficiency. It is rarely a cause of treatment disruption (0.18-4%). Conclusion: Clinicians should be aware of this side effect, especially in patients who may be at risk of complications of hypercalcemia.

11.
Curr Drug Discov Technol ; 19(3): e301121198426, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34847843

RESUMEN

Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tß-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.


Asunto(s)
Productos Biológicos , Factor A de Crecimiento Endotelial Vascular , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Femenino , Humanos , Factor de Crecimiento Placentario/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Cicatrización de Heridas
12.
RSC Adv ; 12(23): 14328-14341, 2022 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-35702201

RESUMEN

This study evaluates the corrosion inhibition property of the aqueous and alcoholic leaf extracts of the medicinal plant Ayapana triplinervis. The major components in the extracts are thymohydroquinone dimethyl ether (THQ) and coumarin. It is clear from the weight-loss studies that the water extract of the leaves (AYW) is superior to the alcoholic extract (AYA) in terms of offering corrosion inhibition. The 96% efficiency of 4% (v/v) AYW in 0.5 N HCl at room temperature changes to 84.62% at 323 K. The mixed-type inhibition behaviour of AYW shows slight dominance in the anodic direction. Studies suggest the multilayer adsorption of phytochemicals on the metal surface and that the adsorption follows the Temkin model. Theoretical studies using DFT and BIOVIA Materials Studio investigations establish THQ as a good inhibitor with high adsorption characteristics. Even though the concentration of coumarin in the extract is low, its presence in the extract facilitates the adsorption of THQ on the metal surface, which is evident from the MD simulation study. The changes in the surface topography and elemental composition of the metal specimen in the inhibited and uninhibited solution are monitored by SEM and EDX spectral studies. XPS data support the presence of both THQ and coumarin on the metal surface and the existence of co-ordinate bonding between the metal's d orbital and the O atoms of THQ. Theoretical and experimental studies support the mixed mode of adsorption of THQ as physisorption followed by chemisorption.

13.
Curr Diabetes Rev ; 18(2): e220321192406, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34225631

RESUMEN

BACKGROUND: In the present scenario, diabetes is a growing health challenge, and its occurrence is growing across the globe. Diabetes, with its complications like diabetic wounds, vasculopathy, neuropathy, wound infections, and oxidative stress, is a serious cause of mortality worldwide. INTRODUCTION: Among the various complications, treatment of diabetic foot and ulcers is one of the major concerns in patients who are suffering from diabetes. The causative factors for this condition include increased oxidative stress, high blood glucose levels, vascular insufficiency, and microbial infections, and many a time, if left untreated, it may even lead to amputations of the lower extremities. The present therapy for the treatment of diabetic wounds mainly involves the use of synthetic moieties and other biotechnology-derived biomolecules, including growth factors. Few plant products are also useful in the treatment of wounds. METHODS: Essential oils derived from various herbs are reported to possess significant wound healing potential and promote blood clotting, help to fight infections, and accelerate the wound healing process. Hence, the present review is a systematic analysis of all the available data on the use of the natural oils with their biological source, active phytochemical constituents present, and the probable mechanism of action for the treatment of chronic and diabetic wounds in suitable animal models. A methodical collection of data was performed, and information was searched up to April 2020 in entirety. Key phrases used for the data search include the pathophysiology of wounds, diabetic foot wound and its complications, natural oils for chronic and diabetic wound treatment. RESULTS: This review summarizes the natural oils which are reported in the literature to be beneficial in the treatment of chronic wounds, while some oils have been specifically also studied against wounds in diabetic rats. Essential oils are said to interact with the body pharmacologically, physiologically and psychologically and help in rapid wound healing. However, the majority of the literature studies have demonstrated wound healing activity only in animal models (preclinical data), and further clinical studies are necessary. CONCLUSION: This review provides a platform for further studies on the effective utilization of natural oils in the treatment of chronic and diabetic wounds, especially if oils are to receive credibility in the management of chronic wounds.


Asunto(s)
Diabetes Mellitus Experimental , Pie Diabético , Aceites Volátiles , Amputación Quirúrgica , Animales , Pie Diabético/tratamiento farmacológico , Humanos , Aceites Volátiles/uso terapéutico , Ratas , Cicatrización de Heridas
14.
J Ayurveda Integr Med ; 13(3): 100633, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36174302

RESUMEN

BACKGROUND: Traditional medicinal herbs are widely consumed in developing countries to treat diabetes as they are perceived to be safer, less expensive, and have fewer side effects as compared to the conventional medicines. Diabecon (DB), Himalaya Herbal Healthcare, India is herbal over-the-counter formulation which contains several herbs that are reported in the traditional texts for the treatment of diabetes. The majority of these herbs have been investigated and found to interfere with the cytochrome pathway. The most common oral antihyperglycemic drug used today in clinical practice is Glimepiride (GP).The CYP2C9 enzyme is mainly responsible for the metabolism of GP. Herein we hypothesize that the co-administration of GP with DB may result in possible Herb-Drug Interactions (HDIs) as DB has the potential to significantly inhibit the CYP2C9 enzyme. OBJECTIVE: In the current study, the pharmacokinetic and pharmacodynamic interactions of GP (0.82 mg/kg) with DB (110.95 mg/kg) was investigated in diabetes induced (Nicotinamide-STZ) rats by co-administering both drugs orally for 21 days. MATERIALS AND METHODS: For the study of the HDI, Bioanalytical RP-HPLC/PDA method for quantifying GP in plasma of rats was developed and validated as per US-FDA guidelines. In vivo pharmacokinetic and pharmacodynamic parameters were studied on day 1 and day 21 post administration. RESULTS: The RP-HPLC/PDA method was successfully employed for quantification of GP in the PK studies. The co-administration of GP and DB in diabetic rats resulted in beneficial pharmacodynamic interactions, but there were no notable changes in the pharmacokinetic parameters of GP. CONCLUSION: This current investigation in an animal model suggests that co-administration of GP and DB may have significant therapeutic benefits in the treatment of diabetes; however, additional research, randomized clinical trials or case studies in humans, is needed.

15.
Artículo en Inglés | MEDLINE | ID: mdl-36845575

RESUMEN

Objectives: To identify risk factors for severe disease and death among patients with diabetes and coronavirus disease 2019 (COVID-19) infection. Methods: This retrospective cohort study conducted at three hospitals included 733 consecutive patients with DM admitted with confirmed COVID-19 (March 1 - December 31, 2020). Multivariable logistic regression was performed to identify predictors of severe disease and death. Results: The mean age was 67.4 ± 14.3 years, 46.9% were males and 61.5% were African American. Among all patients, 116 (15.8%) died in the hospital. A total of 317 (43.2%) patients developed severe disease, 183 (25%) were admitted to an ICU and 118 (16.1%) required invasive mechanical ventilation. Increasing BMI (OR, 1.13; 95% CI, 1.02-1.25), history of chronic lung disease (OR, 1.49; 95% CI, 1.05-2.10) and increasing time since the last HbA1c test (OR, 1.25; 95% CI, 1.05-1.49) were the preadmission factors associated with increased odds of severe disease. Preadmission use of metformin (OR, 0.67; 95% CI, 0.47-0.95) or GLP-1 agonists (OR, 0.49; 95% CI, 0.27-0.87) was associated with decreased odds of severe disease. Increasing age (OR, 1.21; 95% CI, 1.09-1.34), co-existing chronic kidney disease greater than stage 3 (OR, 3.38; 95% CI, 1.67-6.84), ICU admission (OR, 2.93; 95% CI, 1.28-6.69) and use of invasive mechanical ventilation (OR, 8.67, 95% CI, 3.88-19.39) were independently associated with greater odds of in-hospital death. Conclusion: Several clinical characteristics were identified to be predictive of severe disease and in-hospital death among patients with underlying diabetes hospitalized with COVID-19.

16.
Sci Transl Med ; 14(660): eabj7465, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-36044595

RESUMEN

Arterial and venous thrombosis constitutes a major source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that arterial and venous thrombosis can occur in the same populations, suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, antithrombotic therapies targeting the immune system for therapeutics gain are lacking. Here, we show that neutrophils are key effectors of both arterial and venous thrombosis and can be targeted through immunoregulatory nanoparticles. Using antiphospholipid antibody syndrome (APS) as a model for arterial and venous thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation through genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils clustered P-selectin glycoprotein ligand 1 (PSGL-1) by cortical actin remodeling, thereby increasing adhesion potential at sites of thrombosis. Targeting clustered PSGL-1 using nanoparticles attenuated neutrophil-mediated thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutrophils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.


Asunto(s)
Síndrome Antifosfolípido , Trombosis , Trombosis de la Vena , Anticuerpos Antifosfolípidos , Humanos , Neutrófilos/metabolismo , Trombosis/etiología
17.
Saudi Pharm J ; 19(4): 221-31, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23960763

RESUMEN

A stability indicating high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-diabetic drugs, nateglinide and metformin hydrochloride in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Method was validated according to ICH guidelines. The correlation coefficients of calibration curves were found to be 0.996 and 0.995 in the concentration range of 200-2400 and 500-3000 ng band(-1) for nateglinide and metformin, respectively. The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin hydrochloride. The method had the potential to determine these drugs simultaneously from dosage forms without any interference of the tablets excipients. Nateglinide and metformin hydrochloride were also subjected to acid, base, oxidation, wet, heat and photo-degradation studies. The degradation products obtained were well resolved from the pure drugs with significantly different Rf values. As the method could effectively separate the drugs from its degradation products, it can be used for stability-indicating analysis.

18.
Front Psychol ; 12: 664638, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34093360

RESUMEN

A person's financial well-being (FWB) is the complete contentment gained from one's present financial condition. This has a powerful impact on the entire achievement of an employee's "well-being." Researchers, financial analysts, financial planners, educationists, and economists have explored the "enablers" to improve employees' living standards by investigating the possible "FWB" resources for decades. There is no literature available to show the connection between social capital theory, social exchange theory (SET), social cognitive theory (SCT), financial literacy and FWB, and employees' financial knowledge sharing a moderator to expand the complete FWB.

19.
Tour Manag Perspect ; 37: 100786, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33391988

RESUMEN

The COVID-19 pandemic struck the tourism industry severely. Based on the review of 35 papers that studied the tourism industry in the wake of the pandemic, we propose a resilience-based framework for reviving the global tourism industry post-COVID-19. Our framework outlines four prominent factors for building resilience in the industry: government response, technology innovation, local belongingness, and consumer and employee confidence. We argue that using such inclusive resilience; the tourism industry may transform into a new global economic order characterized by sustainable tourism, society's well-being, climate action, and the involvement of local communities. We also offer directions for future research in the area.

20.
J Chromatogr Sci ; 59(4): 371-380, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33434916

RESUMEN

Herbals that are widely consumed as therapeutic alternatives to conventional drugs for cardiovascular diseases, may lead to herb-drug interactions (HDIs). Atorvastatin (ATR) is drug of choice for hyperlipidemia and is extensively metabolized through CYP3A4 enzyme. Thus, we postulate that concomitant administration of ATR with piperine (PIP, potent inhibitor of CYP3A4 enzyme)/ridayarishta (RID, cardiotonic herbal formulations containing PIP) may lead to potential HDI. A simple, accurate, sensitive high-performance liquid chromatography-photodiode array detection method using Kromasil-100 C18 column, mobile phase acetonitrile: 30 mM phosphate buffer (55:45 v/v) pH 4.5 with flow rate gradient programming was developed to study the potential HDI in rats. Method was found to be linear (2-100 ng/mL) with Lower Limit of Detection (LLOD) 2 ng/mL. The precision (%CV < 15%), accuracy (-1.0 to -10% R.E) with recoveries above 90% from rat plasma of ATR and IS were obtained. The pharmacokinetic (PK) interactions studies on co-administration of ATR (8.4 mg/kg, p.o.) with PIP (35 mg/kg, p.o.), demonstrated a threefold increase in Cmax of ATR (P < 0.01) with significant increase in AUC0-t/AUC0-∞ compared to ATR alone indicating potential PK-HDI. However co-administration of RID (4.2 mL/kg, p.o.) showed less significant changes (P > 0.05) indicating low HDI. The pharmacodynamic effects/interactions study (TritonX-100 induced hyperlipidemic model in rats) suggested no significant alterations in the lipid profile on co-administration of PIP/RID with ATR, indicating that there may be no significant pharmacodynamic interactions.


Asunto(s)
Alcaloides , Atorvastatina , Benzodioxoles , Cromatografía Líquida de Alta Presión/métodos , Piperidinas , Alcamidas Poliinsaturadas , Alcaloides/sangre , Alcaloides/química , Alcaloides/farmacocinética , Animales , Atorvastatina/sangre , Atorvastatina/química , Atorvastatina/farmacocinética , Benzodioxoles/sangre , Benzodioxoles/química , Benzodioxoles/farmacocinética , Interacciones de Hierba-Droga , Límite de Detección , Modelos Lineales , Piperidinas/sangre , Piperidinas/química , Piperidinas/farmacocinética , Extractos Vegetales/sangre , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Alcamidas Poliinsaturadas/sangre , Alcamidas Poliinsaturadas/química , Alcamidas Poliinsaturadas/farmacocinética , Ratas , Ratas Wistar , Reproducibilidad de los Resultados
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