RESUMEN
Intraventricular hemorrhage (IVH) results in periventricular inflammation, hypomyelination of the white matter, and hydrocephalus in premature infants. No effective therapy exists to prevent these disorders. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists reduce inflammation, alleviate free radical generation, and enhance microglial phagocytosis, promoting clearance of debris and red blood cells. We hypothesized that activation of PPAR-γ would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPAR-γ expression in microglia of both preterm human infants and rabbit kits. The treatment with PPAR-γ agonist or PPAR-γ overexpression by adenovirus delivery further elevated PPAR-γ levels in microglia, reduced proinflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPAR-γ-induced genes for purinergic signaling, cyclic adenosine monophosphate generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-sequencing analyses of microglia revealed PPAR-γ-triggered down-regulation of several proinflammatory genes and transcripts having roles in Parkinson's disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPAR-γ activation enhanced myelination and neurological function in kits with IVH. This also enhanced microglial phagocytosis of red blood cells but did not reduce hydrocephalus. Treatment with PPAR-γ agonist might enhance myelination and neurological recovery in premature infants with IVH.
Asunto(s)
Hemorragia Cerebral Intraventricular/metabolismo , Proteínas de la Mielina/biosíntesis , PPAR gamma/metabolismo , Sistemas de Transporte de Aminoácidos Acídicos/deficiencia , Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Animales , Animales Recién Nacidos , Antiportadores/deficiencia , Antiportadores/metabolismo , Hemorragia Cerebral Intraventricular/patología , Modelos Animales de Enfermedad , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/metabolismo , Humanos , Recien Nacido Prematuro , Microglía/metabolismo , Enfermedades Mitocondriales/metabolismo , Oligodendroglía/patología , PPAR gamma/agonistas , Trastornos Psicomotores/metabolismo , Conejos , Rosiglitazona/farmacología , Análisis de Secuencia de ARN/métodosAsunto(s)
Azitromicina/administración & dosificación , Betacoronavirus/aislamiento & purificación , Colitis , Infecciones por Coronavirus , Hidroxicloroquina/administración & dosificación , Pandemias , Neumonía Viral , Sulfato de Zinc/administración & dosificación , Adulto , Anciano , Antibacterianos/administración & dosificación , Antimaláricos/administración & dosificación , Astringentes/administración & dosificación , COVID-19 , Colitis/diagnóstico , Colitis/etiología , Colitis/fisiopatología , Colitis/terapia , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/etiología , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Radiografía Abdominal/métodos , SARS-CoV-2 , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Increased incidence of kidney injury has been seen in patients with COVID-19. However, less is known about COVID-19 susceptibility and outcomes in end-stage renal disease (ESRD) patients on hemodialysis (HD). Reduced angiotensin-converting enzyme 2 (ACE-2) from SARS-CoV-2 binding and increased angiotensin II (Ang-II) activity have been suggested as mechanisms for COVID-19 renal pathophysiology. MATERIALS AND METHODS: In this case series, we analyzed the data of 3 patients with ESRD who had a delay in receiving their regular HD. Reduced oxygen requirement, resolved hyperkalemia, and normalized fluid status were used for the basis of discharge. RESULTS: Presenting symptoms included fever, dyspnea, and dry cough. Laboratory markers were characteristic for COVID-19, such as lymphopenia, elevated D-dimer, C-reactive protein (CRP), and interleukin 6 (IL-6). All 3 of our reported patients required urgent HD upon admission. However, we report no fatalities in our case series, and our patients did not have a severe course of illness requiring endotracheal intubation. We reviewed COVID-19 pathophysiology and how patients with ESRD on HD may be particularly at risk for infection. CONCLUSION: New renal failure or ESRD sequelae, such as hyperkalemia, uremic encephalopathy, and fluid overload, can be exacerbated by a delay in receiving HD due to COVID-19 infection. Both direct COVID-19 infection and the challenges this pandemic creates to health care logistics present unique threats to ESRD patients on HD.
RESUMEN
Coronavirus disease-19 (COVID-19) pandemic is associated with high morbidity and mortality. COVID-19, which is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2), affects multiple organ systems through a myriad of mechanisms. Afflicted patients present with a vast constellation of symptoms, from asymptomatic disease to life-threatening complications. The most common manifestations pertain to mild pulmonary symptoms, which can progress to respiratory distress syndrome and venous thromboembolism. However, in patients with renal failure, life-threatening cardiac abnormalities can ensue. Various mechanisms such as viral entry through Angiotensin receptor (ACE) affecting multiple organs and thus releasing pro-inflammatory markers have been postulated. Nevertheless, the predictors of various presentations in the affected population remain elusive. An ameliorated understanding of the pathology and pathogenesis of the viral infection has led to the development of variable treatment options, with many more that are presently under trial. This review article discusses the pathogenesis of multiple organ involvement secondary to COVID-19 infection in infected patients.
RESUMEN
BACKGROUND: Transradial (TR) percutaneous coronary intervention (PCI) is a preferable PCI route. The complication difference between TR and TF approaches is controversial. METHODS: PubMed, Embase, and the Cochrane databases were queried for PCI outcomes of TR TF in STEMI for major cardiac and cerebrovascular events (MACCE), major bleeding, and mortality. The odds ratio (OR) was calculated using the random-effect model. RESULTS: We included 56 studies comprising of 68,733 patients (TR, n = 26,179; TF, n = 42,537). TR-PCI was associated with statistically significant lower odds of MACCE (OR = 0.66, 95% CI: 0.49-0.88, p-value = 0.005), major bleeding (OR = 0.47, 95% CI 0.32-0.68, p-value<0.001), mortality (OR = 0.59, 95% CI 0.43-0.80, p-value<0.001) at in hospital follow-up. TR-PCI was associated with statistically significant lower MACCE (OR = 0.59, 95% CI 0.43-0.80, p-value<0.001), major bleeding (OR = 0.58, 95% CI 0.49-0.68, p-value<0.001), and mortality (OR = 0.61, 95% CI 0.44-0.86, p-value = 0.005) at 30-day follow-up. The same difference was seen at 1-year. CONCLUSION: TR-PCI was associated with lower odds of MACCE, major bleeding, and mortality during short- and long-term follow-up.
Asunto(s)
Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/terapia , Arteria Femoral , Hemorragia/etiología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Arteria Radial , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/mortalidad , Resultado del TratamientoRESUMEN
Infective endocarditis is a significant healthcare burden due to the associated high mortality and complications. Endocarditis caused by both Candida albicans (C. albicans) and non-Candida albicans Candida (NCAC) species has been associated with a substantial rise in in-hospital morbidity and mortality. We used the Pubmed database to identify 47 out of 101 articles that had met our inclusion and exclusion criteria. We had put in place a broad inclusion criterion with no age or gender restrictions. These 47 articles included abstracts, 11 review articles, 13 case reports, 10 research articles, 1 clinical trial report, 1 meta-analysis, and other research articles. And they comprehensively cover the pathogenesis, risk factors, and management of infections caused by C. albicans and NCAC species in the past 26 years. The articles we scanned provided us with information on different associations in correlation to multiple types of Candida species. Here, we discuss the association between Candida and endocarditis, a major cause of morbidity and mortality in both C. albicans and NCAC. We also present our understanding regarding this interesting association and attempt to address some of the recurring questions.
RESUMEN
Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.
RESUMEN
In this project, we are trying to review the articles that discuss the relationship between insulin signaling and Alzheimer's disease (AD). Another focus of this project is to find the best treatment regimen that can reduce the progression of AD in patients with impaired glucose metabolism. We used Pubmed database to collect our data and used the following keywords: Alzheimer's disease, insulin signaling pathway, type 3 diabetes, type 2 diabetes, insulin, and insulin resistance in our revision; we included free articles that were published in the last 10 years and excluded articles that were written in any language other than English. We reviewed 68 articles. Forty-nine out of 68 articles were containing materials that are relevant for this project. We found that there is a relation between AD and the insulin signaling pathway. Insulin signaling pathway impairment leads to hyperphosphorylation of Tau protein, which plays a vital role in AD pathology. The effect of insulin on cognition is bidirectional; the intranasal route of insulin showed to have a promising effect on cognition improvement. Subcutaneous and intravenous insulin can increase the risk of dementia. Further studies are encouraged to use a specific anti-diabetic medication that can reduce the progression of AD.
RESUMEN
A 67-year-old man with a prior heart failure presented with fever, cough and dyspnea for 4 days. Physical examination showed bilateral rales on the lung exam, yet no lower extremity edema. The combination of symptoms, elevated inflammatory markers, normal baseline pro-B-type natriuretic peptide, PaO2/FiO2 < 300 and positive swab suggested coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) rather than heart failure exacerbation. We discuss the challenges in management of ARDS in COVID-19 patients that may initially mimic as acute exacerbation of heart failure.
RESUMEN
Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19.
RESUMEN
This article aims to determine an association between vasculitis and cerebrovascular accidents (CVA) and the ideal management plan to decrease the chances of CVA in vasculitis patients. We also attempt to find a preferred treatment regimen that decreases the complications of CVAs in vasculitis patients, thereby resulting in reduced mortality and morbidity. We reviewed both free-access full-text articles and the abstracts of articles behind a paywall. We used the PubMed database and reviewed 89 articles that matched our inclusion and exclusion criteria. In all, 42 out of the 89 articles had the most relevant data for our article. We used the following keywords to search the database: vasculitis, stroke, cerebrovascular accident, ischemic, arteritis, and steroid. We found an association between subtypes of vasculitis, mostly large vessel vasculitis and CVA. We could not identify a specific cutoff value for specific inflammatory markers that can increase the risk of developing CVA. Besides, there are no formal guidelines for the dosage or the route of administration for corticosteroids, which are the cornerstone of treatment for most vasculitis. We found that male giant cell arteritis (GCA) patients have a higher chance of developing CVA than females, Also interestingly, anemia was found to be protective against CVA development in GCA patients. Sometimes, CVA can happen due to the effects of treatments of some types of vasculitis. We recommend establishing further studies about other subtypes of vasculitis and their associations with stroke.