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2.
Cureus ; 16(1): e52684, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38260109

RESUMEN

Coronary microvascular dysfunction (CMD) is becoming increasingly recognized as an important contributor to the development of ischemic heart diseases. Without obstructive coronary artery disease, the physiological function of the coronary microcirculation can be altered by structural, functional, and molecular factors, leading to myocardial ischemia. CMD can significantly impact the quality of life and prognosis and imposes a huge financial burden on healthcare systems and people. This meta-analysis aims to investigate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for treating CMD. A systematic literature review identified randomized controlled trials (RCTs) comparing ACEIs with placebo in CMD patients. Review Manager, 5.3 for Windows, was utilized. Using the Mantel-Haenszel (M-H) method, improvement in coronary flow reserve (CFR) and systolic blood pressure events was pooled as mean difference (MD) in a meta-analysis model with a fixed effect model, whereas the number of chest pain episodes was pooled as MD with a random effect model. Five randomized controlled trials involving 209 patients were included in the analysis. The analysis demonstrated a statistically significant improvement in CFR in the ACEIs group compared to the placebo group (MD -0.3, 95% CI -0.61 to 0.01, P = 0.05). However, there was no significant difference in the number of chest pain episodes between the ACEIs and placebo groups (MD 1.79, 95% CI -3.99 to 7.58, P = 0.54). Similarly, no significant difference in blood pressure change was observed between the two groups (MD 4.02, 95% CI -3.25 to 11.28, P = 0.28). In conclusion, the appropriate treatment for CMD is a source of contention because adequate data is lacking. Our findings suggest that ACEIs may have a positive effect on improving CFR in patients with microvascular angina. However, ACEIs did not demonstrate a significant impact on the number of chest pain episodes or systolic blood pressure in this patient population. Further research, including RCTs with larger sample sizes and longer follow-up durations, is warranted to provide more conclusive evidence on the role of ACEIs in CMD management.

3.
ArXiv ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-37332564

RESUMEN

Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths annually and 10 million new cases reported each year. The causative organism, Mycobacterium tuberculosis (Mtb) can take nearly 40 days to culture, a required step to determine the pathogen's antibiotic susceptibility. Both rapid identification of Mtb and rapid antibiotic susceptibility testing (AST) are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the MtB complex strain Bacillus Calmette Guerin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin and amikacin, as well as a pan susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and in patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all 5 BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5000. We show how this instrument and our machine learning model enables combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.

4.
Cureus ; 15(11): e49645, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38033439

RESUMEN

Evidence from preclinical and clinical studies suggests that human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) may be useful in treating heart failure and acute myocardial infarction (MI). However, the effects of stem cell therapy on patients with heart failure remain the subject of ongoing controversy, and the safety and effectiveness of HUC-MSCs therapy have not yet been proven. To date, there has been no systematic overview and meta-analysis of clinical studies using HUC-MSCs therapy for heart failure and MI. The purpose of this study is to assess the safety and efficacy of HUC-MSC therapy versus a placebo in patients with heart failure and MI. While preparing this systematic review and meta-analysis, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer literature search of PubMed was performed. We considered randomized controlled trials (RCTs) that reported data on the safety and efficacy of HUC-MSC transplantation in patients with heart failure and MI. Two investigators independently searched the literature, extracted data, and rated the quality of the included research. Pooled data were analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was ejection fraction (EF), whereas the secondary outcomes were readmission and mortality rates. Three RCTs (201 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of risk of readmission (risk ratio = 0.5, 95% confidence interval (CI) = 0.22-1.15, p = 0.10) as well as mortality rate (risk ratio = 0.44, 95% CI = 0.14-1.44, p = 0.18). However, there was an improvement in EF in patients who received HUC-MSCs compared to placebo after 12 months of transplantation (mean difference (MD) = 3.21, 95% CI = 2.91-3.51, p < 0.00001). At the six-month follow-up period, there was no significant improvement in EF (MD = 1.30, 95% CI = -1.94-4.54), p = 0.43), indicating that the duration of follow-up can shape the response to therapy. Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates. Existing evidence is insufficient to confirm the efficacy of HUC-MSCs for broader therapeutic applications. Therefore, additional double-blind RCTs with larger sample sizes are required.

6.
Curr Diabetes Rev ; 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37592776

RESUMEN

BACKGROUND: Iron plays a key role in the regulation of body iron homeostasis and is used as a clinical marker for iron deficiency (ID) and hemochromatosis. The idea that iron dysregulation may contribute to various metabolic diseases, such as obesity, insulin resistance, MetS, and T2DM, is a hot topic of discussion. AIM: The aim of this study is to investigate the relationship insulin resistance, iron status markers, and body weight in a sample of Egyptian population. METHODS: A case control study was conducted on 90 subjects with age ranging from 18 to 70 years old from a diabetes outpatient clinic, and they were divided to three groups: Group I, non-obese-non-diabetic as the control group; Group II, obese-non-diabetic; and Group III, obese-diabetic. RESULTS: In our study, there was no statistically significant difference between the three studied groups regarding the different iron parameters. Similarly, we found that neither HOMA-IR nor body weight had a significant correlation with iron status markers. On the contrary, we detected significant positive correlations between the TIBC and the fasting blood glucose, between the serum iron and the LDL, between the TSAT and the systolic blood pressure, and between the HOMA-IR and hematocrit. CONCLUSION: Our study demonstrated no direct statistical significant relationship between the different iron parameters, obesity, and insulin resistance, either in the diabetic or non-diabetic subjects. This may be due to the complex metabolic dysregulation and the small number of the sample for future investigations.

7.
Nano Lett ; 23(6): 2065-2073, 2023 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-36856600

RESUMEN

Identifying pathogens in complex samples such as blood, urine, and wastewater is critical to detect infection and inform optimal treatment. Surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) can distinguish among multiple pathogen species, but processing complex fluid samples to sensitively and specifically detect pathogens remains an outstanding challenge. Here, we develop an acoustic bioprinter to digitize samples into millions of droplets, each containing just a few cells, which are identified with SERS and ML. We demonstrate rapid printing of 2 pL droplets from solutions containing S. epidermidis, E. coli, and blood; when they are mixed with gold nanorods (GNRs), SERS enhancements of up to 1500× are achieved.We then train a ML model and achieve ≥99% classification accuracy from cellularly pure samples and ≥87% accuracy from cellularly mixed samples. We also obtain ≥90% accuracy from droplets with pathogen:blood cell ratios <1. Our combined bioprinting and SERS platform could accelerate rapid, sensitive pathogen detection in clinical, environmental, and industrial settings.


Asunto(s)
Bioimpresión , Nanopartículas del Metal , Espectrometría Raman/métodos , Escherichia coli , Oro/química , Staphylococcus epidermidis , Inteligencia Artificial , Nanopartículas del Metal/química
8.
Mol Ther Methods Clin Dev ; 28: 262-271, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36816757

RESUMEN

The safety and efficacy of lentivirus-mediated gene therapy was recently demonstrated in five male patients with Fabry disease-a rare X-linked lysosomal storage disorder caused by GLA gene mutations that result in multiple end-organ complications. To evaluate the risks of clonal dominance and leukemogenesis, which have been reported in multiple gene therapy trials, we conducted a comprehensive DNA insertion site analysis of peripheral blood samples from the five patients in our gene therapy trial. We found that patients had a polyclonal integration site spectrum and did not find evidence of a dominant clone in any patient. Although we identified vector integrations near proto-oncogenes, these had low percentages of contributions to the overall pool of integrations and did not persist over time. Overall, we show that our trial of lentivirus-mediated gene therapy for Fabry disease did not lead to hematopoietic clonal dominance and likely did not elevate the risk of leukemogenic transformation.

9.
Braz J Cardiovasc Surg ; 38(3): 405-406, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-36459477

RESUMEN

Recurrent pericardial effusion is commonly encountered in neoplastic and infective disorders. Intervention is compulsory in patients with unstable hemodynamics and tamponading effusion. Surgical options include: pericardiocentesis, subxiphoid pericardiostomy, and pericardial window. The latter has proved to have lower incidence of recurrence; however, the technique has been continuously refined to improve the recurrence-free survival and decrease postoperative morbidity. We herein present a novel simple modification to minimize recurrence by anchoring the free edges of pericardial fenestration overlying the superior vena cava and right atrium to the chest wall. Follow-up showed no recurrence compared to 3.5% in the conventional procedure.


Asunto(s)
Derrame Pericárdico , Vena Cava Superior , Humanos , Vena Cava Superior/cirugía , Derrame Pericárdico/cirugía , Derrame Pericárdico/etiología , Técnicas de Ventana Pericárdica , Hemodinámica , Atrios Cardíacos/cirugía
10.
Rev. bras. cir. cardiovasc ; 38(3): 405-406, 2023. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1441207

RESUMEN

ABSTRACT Recurrent pericardial effusion is commonly encountered in neoplastic and infective disorders. Intervention is compulsory in patients with unstable hemodynamics and tamponading effusion. Surgical options include: pericardiocentesis, subxiphoid pericardiostomy, and pericardial window. The latter has proved to have lower incidence of recurrence; however, the technique has been continuously refined to improve the recurrence-free survival and decrease postoperative morbidity. We herein present a novel simple modification to minimize recurrence by anchoring the free edges of pericardial fenestration overlying the superior vena cava and right atrium to the chest wall. Follow-up showed no recurrence compared to 3.5% in the conventional procedure.

11.
Cytotherapy ; 24(7): 699-710, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35473998

RESUMEN

Pancreatic cancer is a highly lethal cancer characterized by local invasiveness, early metastasis, recurrence and high resistance to current therapies. Extensive stroma or desmoplasia is a key histological feature of the disease, and interactions between cancer and stromal cells are critical for pancreatic cancer development and progression. Mesenchymal stromal cells [MSCs] exhibit preferential tropism to primary and metastatic tumor sites and may either suppress or support tumor growth. Although MSCs represent a potential source of pancreatic cancer stroma, their contribution to pancreatic tumor growth remains poorly known. Here, we show that bone marrow MSCs significantly contribute to pancreatic cancer growth in vitro and in vivo. Furthermore, MSCs create a pro-carcinogenic microenvironment through the release of key factors mediating growth and angiogenesis, including interleukin (IL)-6, IL-8, vascular endothelial growth factor and activation of STAT3 signaling in tumor cells. IL-6 released by MSCs was largely responsible for the pro-tumorigenic effects of MSCs. Knockdown of IL-6 expression in MSCs by small interfering RNA (siRNA) abolished the MSC growth-promoting effect in vitro, reducing tumor cell proliferation and clonogenic potential. In addition, in a heterotopic nude mouse model of human pancreatic tumor xenografts, blockade of IL-6 with the anti-IL-6 receptor antibody, tocilizumab, or of its downstream effector STAT3 with the small molecule STAT3 inhibitor S3I-201, abrogated MSC-mediated tumor promotion and delayed tumor formation significantly. Our data demonstrate that MSCs promote pancreatic cancer growth, with IL-6 produced by MSCs playing a pivotal role.


Asunto(s)
Interleucina-6/metabolismo , Células Madre Mesenquimatosas , Neoplasias Pancreáticas , Animales , Médula Ósea/metabolismo , Línea Celular Tumoral , Humanos , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neoplasias Pancreáticas
12.
Nat Rev Cancer ; 22(4): 208-222, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35031778

RESUMEN

Ependymomas are rare central nervous system tumours that can arise in the brain's supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.


Asunto(s)
Ependimoma , Recurrencia Local de Neoplasia , Biología , Ependimoma/genética , Ependimoma/metabolismo , Ependimoma/terapia , Humanos , Oncogenes , Microambiente Tumoral
13.
J Biomol Struct Dyn ; 40(1): 276-289, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-32851933

RESUMEN

UCHL3 (ubiquitin C-terminal hydrolase-L3) is a de-ubiquitinating enzyme involved in the homologous recombination repair mechanism of double-strand breaks (DBS) of the DNA. Multiple studies indicated that UCHL3 inhibitors could be used in combination therapy with high therapeutic efficacy against cancer thus highlighting the validity of directing research against UCHL3 as a druggable target in oncology. In this study, a combination of virtual screening methods was utilized to identify new potential UCHL3 inhibitors. A series of UCHL3 ligands were identified by applying a combination of cheminformatics and molecular modeling filtration techniques to a ChemBl database of over two million small molecules viz. Lipinski's Rule of Five, Veber's rule, pharmacophore model, Hierarchical molecular docking, Pan-assay Interference Compounds (PAINS) alerts, toxicity filter, and single-point Molecular mechanics Poisson/Boltzmann surface area (MM/PBSA) docking pose rescoring. This multi-layer filtration strategy led to the identification of twenty-one compounds as potential UCHL3 inhibitors that were subsequently subjected to a 50 ns molecular dynamics (MD) simulations predict the stability of their ligand-protein complexes. Furthermore, MM/PBSA calculations based on MD trajectories were performed, and the energy contribution per residue to the binding energy was calculated. Three compounds, 1, 2 and 3, were finally recognized as having the highest potential of being UCHL3 inhibitors. Therefore, those were used for binding mode analysis to the UCHL3 active site, leading to identification of four residues as key for binding viz. Pro8, Leu55, Val166, and Leu168.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Simulación de Dinámica Molecular , Neoplasias , Detección Precoz del Cáncer , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Reparación del ADN por Recombinación , Ubiquitina Tiolesterasa
14.
J Biomol Struct Dyn ; 40(3): 1109-1119, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-32936048

RESUMEN

Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel ß strands, ß1' and ß2', and the small helix α1'. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma.


Asunto(s)
COVID-19 , Linfopenia , Basigina , Humanos , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo
15.
Cureus ; 13(7): e16635, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34462676

RESUMEN

The emergence of the coronavirus disease 2019 (COVID-19) pandemic has made us appreciate how important it is to quickly develop treatments and save lives. The race to develop a vaccine for this novel coronavirus began as soon as the pandemic emerged. Time was the only limiting factor. From the first vaccine developed in 1796 against smallpox to the latest COVID-19 vaccine, there have been several vaccines that have reduced the burden of disease, with the associated mortality and morbidity. Over the years we have seen many new advancements in organism isolation, cell culture, whole-genome sequencing, and recombinant nuclear techniques. These techniques have greatly facilitated the development of vaccines. Each vaccine has its own development story and there is much wisdom to be gained from learning about breakthroughs in vaccine development.

16.
J Mol Graph Model ; 106: 107940, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34015577

RESUMEN

Selective antagonists for the kappa opioid receptor (KOP) have the potential to treat opiate and alcohol addiction, as well as depression and other CNS disorders. Over the years, the development of KOP-selective antagonists yielded very few successful compounds. Recently, N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines have emerged as a novel class of pure opioid receptor antagonists, including the marketed Mu opioid receptor (MOP) peripheral antagonist Alvimopan and the potent KOP antagonist JDTic. However, the selectivity determinants of this class of compounds towards the opioid receptor subtypes are still vague and understudied. In this work, we have performed Molecular Dynamics (MD) simulation to gain insights into the differential binding of this class of compounds into KOP, as exemplified by Alvimopan and JDTic. Our study indicated that the selectivity largely depends on ligands interaction with the selectivity pocket formed by Val108, Thr111, and Val118, supported by two additional polar and hydrophobic contacts with Asp138 and Trp287, respectively. Our results also demonstrate, for the first time, that non-morphinan ligands can still adopt the "message-address model" for KOP efficacy and selectivity by binding to Glu297.


Asunto(s)
Simulación de Dinámica Molecular , Receptores Opioides kappa , Ligandos , Antagonistas de Narcóticos , Receptores Opioides
17.
Nano Lett ; 20(10): 7655-7661, 2020 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-32914987

RESUMEN

Surface-enhanced Raman spectroscopy (SERS) is a promising cellular identification and drug susceptibility testing platform, provided it can be performed in a controlled liquid environment that maintains cell viability. We investigate bacterial liquid-SERS, studying plasmonic and electrostatic interactions between gold nanorods and bacteria that enable uniformly enhanced SERS. We synthesize five nanorod sizes with longitudinal plasmon resonances ranging from 670 to 860 nm and characterize SERS signatures of Gram-negative Escherichia coli and Serratia marcescens and Gram-positive Staphylococcus aureus and Staphylococcus epidermidis bacteria in water. Varying the concentration of bacteria and nanorods, we achieve large-area SERS enhancement that is independent of nanorod resonance and bacteria type; however, bacteria with higher surface charge density exhibit significantly higher SERS signal. Using cryo-electron microscopy and zeta potential measurements, we show that the higher signal results from attraction between positively charged nanorods and negatively charged bacteria. Our robust liquid-SERS measurements provide a foundation for bacterial identification and drug testing in biological fluids.


Asunto(s)
Mycobacterium tuberculosis , Espectrometría Raman , Microscopía por Crioelectrón , Oro , Pruebas de Sensibilidad Microbiana , Electricidad Estática
18.
J Chem Phys ; 152(24): 240902, 2020 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-32610995

RESUMEN

In a pandemic era, rapid infectious disease diagnosis is essential. Surface-enhanced Raman spectroscopy (SERS) promises sensitive and specific diagnosis including rapid point-of-care detection and drug susceptibility testing. SERS utilizes inelastic light scattering arising from the interaction of incident photons with molecular vibrations, enhanced by orders of magnitude with resonant metallic or dielectric nanostructures. While SERS provides a spectral fingerprint of the sample, clinical translation is lagged due to challenges in consistency of spectral enhancement, complexity in spectral interpretation, insufficient specificity and sensitivity, and inefficient workflow from patient sample collection to spectral acquisition. Here, we highlight the recent, complementary advances that address these shortcomings, including (1) design of label-free SERS substrates and data processing algorithms that improve spectral signal and interpretability, essential for broad pathogen screening assays; (2) development of new capture and affinity agents, such as aptamers and polymers, critical for determining the presence or absence of particular pathogens; and (3) microfluidic and bioprinting platforms for efficient clinical sample processing. We also describe the development of low-cost, point-of-care, optical SERS hardware. Our paper focuses on SERS for viral and bacterial detection, in hopes of accelerating infectious disease diagnosis, monitoring, and vaccine development. With advances in SERS substrates, machine learning, and microfluidics and bioprinting, the specificity, sensitivity, and speed of SERS can be readily translated from laboratory bench to patient bedside, accelerating point-of-care diagnosis, personalized medicine, and precision health.


Asunto(s)
Biomarcadores/análisis , Enfermedades Transmisibles/diagnóstico , Espectrometría Raman/métodos , Algoritmos , Aptámeros de Nucleótidos/química , Humanos , Aprendizaje Automático , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Impresión Molecular , Polímeros/química
19.
Acc Chem Res ; 53(3): 588-598, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-31913015

RESUMEN

Chirality in Nature can be found across all length scales, from the subatomic to the galactic. At the molecular scale, the spatial dissymmetry in the atomic arrangements of pairs of mirror-image molecules, known as enantiomers, gives rise to fascinating and often critical differences in chemical and physical properties. With increasing hierarchical complexity, protein function, cell communication, and organism health rely on enantioselective interactions between molecules with selective handedness. For example, neurodegenerative and neuropsychiatric disorders including Alzheimer's and Parkinson's diseases have been linked to distortion of chiral-molecular structure. Moreover, d-amino acids have become increasingly recognized as potential biomarkers, necessitating comprehensive analytical methods for diagnosis that are capable of distinguishing l- from d-forms and quantifying trace concentrations of d-amino acids. Correspondingly, many pharmaceuticals and agrochemicals consist of chiral molecules that target particular enantioselective pathways. Yet, despite the importance of molecular chirality, it remains challenging to sense and to separate chiral compounds. Chiral-optical spectroscopies are designed to analyze the purity of chiral samples, but they are often insensitive to the trace enantiomeric excess that might be present in a patient sample, such as blood, urine, or sputum, or pharmaceutical product. Similarly, existing separation schemes to enable enantiopure solutions of chiral products are inefficient or costly. Consequently, most pharmaceuticals or agrochemicals are sold as racemic mixtures, with reduced efficacy and potential deleterious impacts.Recent advances in nanophotonics lay the foundation toward highly sensitive and efficient chiral detection and separation methods. In this Account, we highlight our group's effort to leverage nanoscale chiral light-matter interactions to detect, characterize, and separate enantiomers, potentially down to the single molecule level. Notably, certain resonant nanostructures can significantly enhance circular dichroism for improved chiral sensing and spectroscopy as well as high-yield enantioselective photochemistry. We first describe how achiral metallic and dielectric nanostructures can be utilized to increase the local optical chirality density by engineering the coupling between electric and magnetic optical resonances. While plasmonic nanoparticles locally enhance the optical chirality density, high-index dielectric nanoparticles can enable large-volume and uniform-sign enhancements in the optical chirality density. By overlapping these electric and magnetic resonances, local chiral fields can be enhanced by several orders of magnitude. We show how these design rules can enable high-yield enantioselective photochemistry and project a 2000-fold improvement in the yield of a photoionization reaction. Next, we discuss how optical forces can enable selective manipulation and separation of enantiomers. We describe the design of low-power enantioselective optical tweezers with the ability to trap sub-10 nm dielectric particles. We also characterize their chiral-optical forces with high spatial and force resolution using combined optical and atomic force microscopy. These optical tweezers exhibit an enantioselective optical force contrast exceeding 10 pN, enabling selective attraction or repulsion of enantiomers based on the illumination polarization. Finally, we discuss future challenges and opportunities spanning fundamental research to technology translation. Disease detection in the clinic as well as pharmaceutical and agrochemical industrial applications requiring large-scale, high-throughput production will gain particular benefit from the simplicity and relative low cost that nanophotonic platforms promise.


Asunto(s)
Nanopartículas , Fotones , Aminoácidos/química , Dicroismo Circular , Luz , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Pinzas Ópticas , Estereoisomerismo
20.
Eur Heart J Acute Cardiovasc Care ; 9(3_suppl): S5-S12, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29877737

RESUMEN

BACKGROUND: Sodium nitroprusside is the preferred agent for the treatment of high blood pressure during acute aortic syndrome if blood pressure remains elevated after heart rate control with beta-blockers. The increasing cost of sodium nitroprusside in the USA led us to assess the efficacy and safety of intravenous clevidipine, a calcium channel blocker with quick onset of action, short half-life and significantly lower costs than sodium nitroprusside, in patients presenting with acute aortic syndrome. METHODS: We performed a retrospective chart review of consecutive patients admitted to the Cleveland Clinic Cardiac Intensive Care Unit from 2013-2016 with a diagnosis of acute aortic syndrome. Patients who received intravenous sodium nitroprusside were compared with those receiving intravenous clevidipine. The primary outcome was a significant difference in blood pressure at one, three and six hours. Secondary outcomes included time to achieving blood pressure target and in hospital mortality with rates of hypotension and bradycardia as safety endpoints. RESULTS: A total of 85 patients with suspected acute aortic pathology received clevidipine and 50 received sodium nitroprusside. Clinical and demographic characteristics were similar in both groups, except for a higher incidence of abdominal aortic aneurysm in the clevidipine group and for a trend towards higher use of labetalol in the clevidipine group. There were no significant differences in blood pressure or heart rate at one, three and six hours after starting either infusion. The rates of hypotension, bradycardia and in-hospital mortality did not differ. Time to achieve blood pressure control were also similar between groups. CONCLUSION: Intravenous clevidipine appears to be a safe and effective alternative to sodium nitroprusside for the management of high blood pressure during acute aortic dissection. In the USA, clevidipine could represent a cost effective therapy providing similar outcomes than sodium nitroprusside.


Asunto(s)
Aneurisma de la Aorta Torácica/tratamiento farmacológico , Disección Aórtica/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Piridinas/administración & dosificación , Administración Intravenosa , Anciano , Disección Aórtica/diagnóstico , Disección Aórtica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/fisiopatología , Bloqueadores de los Canales de Calcio/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome
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