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1.
J Cardiol Cases ; 29(4): 161-164, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38646075

RESUMO

Ebstein's anomaly (EA), a congenital cardiac anomaly, is characterized by apical displacement of the tricuspid valve leaflet(s) into the right ventricle. We present the case of a 61-year-old female with a history of EA, Wolff-Parkinson-White syndrome, and patent foramen ovale (PFO), who presented with worsening hypoxia and confusion, in the setting of left lower extremity cellulitis and abscess. The computed tomography (CT) scan of the head showed a cerebellar infarct with hemorrhagic conversion. Magnetic resonance imaging of the head showed a satellite lesion raising concern for the embolic nature of infarcts. After ruling out cardioembolic causes of cerebellar infarction, her presenting symptoms were attributed to paradoxical septic emboli from the left leg abscess (demonstrated on CT scan of the leg). She was deemed a poor candidate for surgical closure of PFO due to contraindication to use heparin (due to the presence of hemorrhagic stroke) and underlying comorbidities. Septic embolization is a rare but dreaded complication in EA patients with PFO. Learning objective: •Paradoxical emboli can occur in patients with Ebstein's anomaly (EA) and patent foramen ovale (PFO).•The mainstay of management in case of paradoxical embolism lies with the identification and treatment of the underlying cause, such as infective endocarditis, deep vein thrombosis, or infectious source, as in the present case.•The surgical correction of PFO in EA patients should be considered when the patient becomes symptomatic with cyanosis, hypoxia, or manifestations of paradoxical emboli.

2.
PLoS Pathog ; 20(1): e1011881, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190392

RESUMO

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.


Assuntos
Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo , Células Endoteliais/metabolismo , Infecções por HIV/metabolismo , Isoformas de Proteínas/metabolismo , Microambiente Tumoral
4.
Asian J Neurosurg ; 18(4): 734-741, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38161619

RESUMO

Introduction Adrenaline-soaked wicks are often employed to decongest nasal mucosa during transsphenoidal pituitary surgeries to ensure proper hemostasis and visibility of the operating field. Considerable debate exists regarding the optimum concentration of adrenaline that strikes a balance between hemostasis as well as the hemodynamic side effects of adrenaline. This study assessed cardiac indices like cardiac output and cardiac index using a FloTrac Vigileo cardiac output monitor to compare two different concentrations of adrenaline used for topical instillation. Materials and Methods 60 adult patients undergoing transsphenoidal pituitary surgery were randomly assigned to receive cotton wicks soaked in adrenaline solution (either 1:100,000 or 1:200,000) for nasal decongestion. Following a standardized anesthetic regime, a FloTrac Vigileo cardiac output monitor was attached with the invasive arterial line for precise monitoring and recording of cardiac indices (cardiac output and cardiac index). Additionally, quality of surgical field (as reported by the operating surgeon) blood loss, incidences of adverse hemodynamic events, and rescue drug usage were recorded. Results No difference in cardiac outputs and cardiac indexes of the patients was observed during baseline to 55 minutes and at 80 minutes and onward, whereas difference rose to statistical significance at the time points of 60 minutes and 70 minutes ( p < 0.05). Other parameters like stroke volume, stroke volume variation, and hemodynamic parameters were similar. Quality of the surgical fields (as reported by the surgeon), intraoperative bleeding, incidences of adverse effects, and frequency of rescue drugs usage were similar. Conclusion Instillation of 1:100,000 dilution of adrenaline solution compared with 1:200,000 for nasal decongestion is associated with significant rise in cardiac output and cardiac index at 60 and 70 minutes of the surgery with similar blood loss and hemodynamic variables. Therefore, the lower concentration of adrenaline can be recommended for usage during transsphenoidal pituitary surgeries.

5.
Cureus ; 14(7): e26815, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35971360

RESUMO

INTRODUCTION: The effectiveness of high-flow nasal oxygenation (HFNO) in patients with hypercapnic respiratory failure (RF) remains controversial. The current study compared the effectiveness of HFNO in patients with hypercapnic RF with conventional oxygen therapy (COT). OBJECTIVES: The primary objective was to compare changes in the partial pressure of carbon dioxide (PaCO2) between those receiving COT and HFNO. The secondary objectives were to compare changes in the partial pressure of oxygen (PaO2), oxygen saturation (SpO2), respiratory rate (RR), serum bicarbonate level, base excess, lactate level, and incidence of the need for non-invasive ventilation (NIV) and mechanical ventilation (MV). METHODS: We recruited 30 patients with mild to moderate hypercapnic RF in the HFNO group, and data of 30 patients from historical controls, who matched the inclusion criteria, were obtained from medical records for comparison (COT group). The study was terminated after two hours, and patients were managed per the existing protocol after that. Arterial blood gas (ABG) analysis was repeated at the baseline, first, second, and third hours. RESULTS: In the COT group, the mean RR at the baseline, first, second, and third hours was 24.5 ± 2.61, 24.9 ± 3.03, 26.03 ± 3.4, and 22.90 ± 1.86, whereas, in the HFNO group, it was 25.93 ± 3.91, 23.00 ± 3.54, 22.50 ± 3.38, and 21.90 ± 3.57, respectively. The mean PaCO2 in the COT vs. HFNO groups was 54.45 ± 5.83 vs. 62.22 ± 9.15, 57.74 ± 6.05 vs. 58.65 ± 10.43, 60.79 ± 7.48 vs. 60.41 ± 11.24, and 55.23 ± 6.63 vs. 56.95 ± 10.31. The mean SpO2 in the COT group at these points of time was 94.50 ± 1.46, 95.4 ± 1.28, 96.10 ± 1.84, and 97.53 ± 2.05, whereas, in the HFNO group, it was 95.40 ± 2.55, 98.63 ± 1.43, 99.00 ± 1.66, and 99.50 ± 1.31, respectively. The patients who needed NIV after the study period were 50% and 36.67% in the COT and HFNO groups, respectively. CONCLUSIONS: There was no change in PaCO2 levels with HFNO, but there was a significant improvement in SpO2 and PaO2 levels and a decreased RR. Following the termination of the study protocol, more patients in the COT group needed NIV than those in the HFNO group.

6.
J Nephrol ; 35(1): 69-85, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35013985

RESUMO

BACKGROUND: Coronavirus disease (COVID-19) has resulted in the death of more than 3.5 million people worldwide. While COVID-19 mostly affects the lungs, different comorbidities can have an impact on its outcomes. We performed an overview of reviews to assess the effect of Chronic Kidney Disease (CKD) on contracting COVID-19, hospitalization, mortality, and disease severity. METHODS: We searched published and preprint databases. We updated the reviews by searching for primary studies published after August 2020, and prioritized reviews that are most updated and of higher quality using the AMSTAR tool. RESULTS: We included 69 systematic reviews and 66 primary studies. Twenty-eight reviews reported on the prevalence of CKD among patients with COVID-19, which ranged from 0.4 to 49.0%. One systematic review showed an increased risk of hospitalization in patients with CKD and COVID-19 (RR = 1.63, 95% CI 1.03-2.58) (Moderate certainty). Primary studies also showed a statistically significant increase of hospitalization in such patients. Thirty-seven systematic reviews assessed mortality risk in patients with CKD and COVID-19. The pooled estimates from primary studies for mortality in patients with CKD and COVID-19 showed a HR of 1.48 (95% CI 1.33-1.65) (Moderate certainty), an OR of 1.77 (95% CI 1.54-2.02) (Moderate certainty) and a RR of 1.6 (95% CI 0.88-2.92) (Low certainty). CONCLUSIONS: Our review highlights the impact of CKD on the poor outcomes of COVID-19, underscoring the importance of identifying strategies to prevent COVID-19 infection among patients with CKD.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Causas de Morte , Hospitalização , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , SARS-CoV-2 , Revisões Sistemáticas como Assunto
7.
Indian Heart J ; 73(1): 91-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33714416

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. METHODS: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies was used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. RESULTS: We collected pooled data on 5967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p < 0.001); and 3.61 (95% CI 2.03-6.43) (p = 0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p = 0.022) and 1.52 (95% CI 1.12-2.05) (p = 0.008) among patients who had pre-existing CHF and hypertension, respectively. CONCLUSION: Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.


Assuntos
Biomarcadores/sangue , COVID-19/complicações , Insuficiência Cardíaca/virologia , COVID-19/mortalidade , Creatina Quinase Forma MB/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Peptídeo Natriurético Encefálico/sangue , Pandemias , Fragmentos de Peptídeos/sangue , Prognóstico , SARS-CoV-2 , Índice de Gravidade de Doença , Taxa de Sobrevida , Troponina/sangue
8.
J Funct Foods ; 87: 104749, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34987616

RESUMO

Colossal amounts of food waste are generated and discarded daily at the expense of financial resources and at a detriment to the environment. One such food waste, okara - a soybean by-product, is valorized in this study by upcycling it into nutritional extracts for micronutrients encapsulation. Micronutrient malnutrition, particularly in the developing world, is a major public health challenge. Herein, okara extracts were obtained through a low-cost extraction process and was subsequently developed as an encapsulant material for micronutrients ß-carotene, and ferrous sulphate encapsulation, using zein as an excipient. Spray-drying, as a scalable technique, was employed to produce various formulations which were assessed for release profiles, shelf-life, ß-carotene antioxidant activity and cell cytotoxicity. Finally, an optimized dual-micronutrient formulation displayed a sequential release with ferrous sulphate releasing in simulated gastric fluid, and ß-carotene releasing predominantly in simulated intestinal fluid. This sequential release profile favors the absorption of both the micronutrients and could potentially enhance their bioavailability.

9.
Int J Nanomedicine ; 15: 4943-4956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764927

RESUMO

BACKGROUND: Hydroxyapatite (HA) [Ca5(PO4)3(OH)] is a naturally occurring calcium phosphate which makes up 60-70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability. PURPOSE: Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking. METHODS: HA particles (300 µg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant. RESULTS: The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion. CONCLUSION: HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.


Assuntos
Colágeno/metabolismo , Durapatita/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Pele/citologia , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Durapatita/química , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Humanos
10.
Small ; 16(34): e2003757, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32686344

RESUMO

Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano-PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano-PAAMs, l-phenylalanine functionalized Nano-PAAM (Nano-pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer-selective properties. The therapeutic efficacy of Nano-pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT-1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano-pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent "double-whammy" anticancer effect. The potential clinical utility of Nano-pPAAM is further investigated using an MDA-MB-231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli.


Assuntos
Antineoplásicos , Aminoácidos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Camundongos , Nanoconjugados , Porosidade
11.
Nat Commun ; 11(1): 1786, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286300

RESUMO

Protein-protein interactions featuring intricate binding epitopes remain challenging targets for synthetic inhibitors. Interactions of NEMO, a scaffolding protein central to NF-κB signaling, exemplify this challenge. Various regulators are known to interact with different coiled coil regions of NEMO, but the topological complexity of this protein has limited inhibitor design. We undertook a comprehensive effort to block the interaction between vFLIP, a Kaposi's sarcoma herpesviral oncoprotein, and NEMO using small molecule screening and rational design. Our efforts reveal that a tertiary protein structure mimic of NEMO is necessary for potent inhibition. The rationally designed mimic engages vFLIP directly causing complex disruption, protein degradation and suppression of NF-κB signaling in primary effusion lymphoma (PEL). NEMO mimic treatment induces cell death and delays tumor growth in a PEL xenograft model. Our studies with this inhibitor reveal the critical nexus of signaling complex stability in the regulation of NF-κB by a viral oncoprotein.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma de Efusão Primária/metabolismo , NF-kappa B/metabolismo , Animais , Linhagem Celular , Dicroísmo Circular , Herpesvirus Humano 8/metabolismo , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfoma de Efusão Primária/genética , Masculino , Camundongos , Microscopia Confocal , Modelos Biológicos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Nanoscale Adv ; 2(10): 4798-4812, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36132939

RESUMO

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formation of a protein corona on the nanodiamond surface. However, a precise understanding of both how the corona forms and evolves and its influence on cytotoxicity is lacking. Here, we investigated protein corona formation and evolution in response to two classes of nanodiamonds, pristine and aminated, and two types of proteins, bovine serum albumin and fibronectin. Specifically, we found that a corona made of bovine serum albumin (BSA), which represents the most abundant protein in blood plasma, reduced nanodiamond agglomeration. Fibronectin (FN9-10), the second most abundant protein found in the plasma, exhibited a significantly higher nanodiamond binding affinity than BSA, irrespective of the nanodiamond surface charge. Finally, nanodiamonds with a BSA corona displayed less cytotoxicity towards nonphagocytic liver cells. However, regardless of the type of corona (FN9-10 or BSA), both classes of nanodiamonds induced substantial phagocytic cell death. Our results emphasise that a precise understanding of the corona composition is fundamental to determining the fate of nanoparticles in the body.

13.
Nanotoxicology ; 13(9): 1210-1226, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31522585

RESUMO

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assays that offer high sensitivity and are label-free. Here we developed 'mini-liver' models using scaffold-free bioprinting and used these models together with label-free nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticle-cell interactions, thus could be considered as a complementary approach to currently used methods.


Assuntos
Sobrevivência Celular , Nanodiamantes , Técnicas de Cultura de Células , Humanos , Fígado/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Case Rep Cardiol ; 2019: 5404365, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428481

RESUMO

Takotsubo cardiomyopathy (TCM), also known as broken heart syndrome or stress-induced cardiomyopathy, is a rare condition with an estimated incidence of 0.02% of all hospitalizations in United States and 2% of all acute coronary syndrome presentations. TCM predominately presents as a transient wall motion abnormality of the left ventricular apex due to emotional or physical stress. Cardiac rupture in the setting of TCM is an extremely rare phenomenon with limited published case reports. We present a case of a 75-year-old female who had cardiac rupture secondary to TCM and performed a literature review using Ovid MEDLINE for published cases showing this association. After the literature review, we found 20 cases showing this association, which are listed in a tabular fashion.

15.
Sci Rep ; 9(1): 727, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679718

RESUMO

Mitochondrial dysfunction underscores aging and diseases. Mitophagy (mitochondria + autophagy) is a quality control pathway that preserves mitochondrial health by targeting damaged mitochondria for autophagic degradation. Hence, molecules or compounds that can augment mitophagy are therapeutic candidates to mitigate mitochondrial-related diseases. However, mitochondrial stress remains the most effective inducer of mitophagy. Thus, identification of mitophagy-inducing regimes that are clinically relevant is favorable. In this study, pomegranate extract (PE) supplementation is shown to stimulate mitophagy. PE activates transcription factor EB (TFEB) to upregulate the expression of autophagy and lysosomal genes for mitochondrial quality control under basal and stress conditions. Basally, PE alters mitochondrial morphology and promotes recruitment of autophagosomes to the mitochondria (mitophagosome formation). Upon onset of mitochondrial stress, PE further augments mitophagosome formation, and engages PINK1 and Parkin to the mitochondria to potentiate mitophagy. This cellular phenomenon of PE-induced mitophagy helps to negate superfluous mitochondrial reactive oxygen species (ROS) production and mitochondrial impairment. Overall, our study highlights the potential of PE supplementation as a physiological therapy to modulate TFEB activity to alleviate mitochondrial dysfunction in aging and mitochondrial-related diseases.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Doenças Mitocondriais/tratamento farmacológico , Extratos Vegetais/farmacologia , Punica granatum/química , Autofagia/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Aptidão Genética/efeitos dos fármacos , Células HeLa , Humanos , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/genética , Mitofagia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
16.
Cureus ; 10(6): e2792, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30112268

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA), historically known as the Churg-Strauss disease, is a small- to medium-sized vessel multi-organ vasculitis with a propensity to involve the heart. EGPA is a rare condition with an estimated annual incidence of one to 4.2 people per million. The cardiac involvement causes significant morbidity and mortality in EGPA patients. Approximately 50% of the deaths in EGPA are related to cardiac disease and occur within the first few months since diagnosis. The current recommendations support evaluation of cardiac involvement by using history, physical exam and multimodality imaging including echocardiogram and cardiac magnetic resonance imaging (CMR). Here, we report a rare case of eosinophilic myocarditis in a 19-year-old patient with EGPA seen on CMR. Pertinent literature is also reviewed. We highlighted the importance of CMR in diagnosing and follow up of EGPA patients.

17.
Pharm Res ; 35(10): 185, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30073514

RESUMO

PURPOSE: Peptides are gaining significant interests as therapeutic agents due to their high targeting specificity and potency. However, their low bioavailability and short half-lives limit their massive potential as therapeutics. The use of dense, solid particles of biodegradable polymer as a universal carrier for peptides also has its challenges, such as inefficient peptide release and low bioactivity. In this paper, it was established that hollow microparticles (h-MPs) instead of solid microparticles (s-MPs), as peptide carriers, could improve the release efficiency, while better preserving their bioactivity. METHODS: Glucagon like Peptide-1 (GLP-1) was encapsulated as a model peptide. Mass loss, average molecular weight changes, intraparticle pH, polymer-peptide interaction and release studies, together with bioactivity assessment of the peptide for s-MPs and h-MPs were systematically analyzed and evaluated for efficacy. RESULTS: The intraparticle pH of s-MPs was as low as 2.64 whereas the pH of h-MPs was 4.99 by day 7. Consequently, 93% of the peptide extracted from h-MPs was still bioactive while only 58% of the peptide extracted from s-MPs was bioactive. Likewise, the cumulative release of GLP-1 by day 14 from h-MPs showed a cumulative amount of 88 ± 8% as compared to 33 ± 6% for s-MPs. CONCLUSIONS: The cumulative release of peptide can be significantly improved, and the bioactivity can be better preserved by simply using h-MPs instead of s-MPs as carriers.


Assuntos
Portadores de Fármacos/química , Peptídeo 1 Semelhante ao Glucagon/química , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Porosidade
18.
Med Dosim ; 43(2): 184-194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29753334

RESUMO

The capabilities of the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) for proton therapy treatment planning are described. Various steps involved in the planning process to produce a 3-dimensional (3D) dose distribution both for the passive scattering and pencil beam scanning proton beam therapy are outlined. Mitigation of range and setup uncertainties through robust optimization is discussed. Use of verification plans for patient treatment field dosimetry quality assurance (QA) is presented. Limitations of the Eclipse TPS and future developments are discussed.


Assuntos
Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos
19.
J Genet Eng Biotechnol ; 16(2): 693-701, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30733790

RESUMO

Rice straw is valuable resource that has been used as substrate for cost effective production of xylanase under solid-state fermentation by a newly isolated white rot fungi, S. commune ARC-11. Out of eleven carbon sources tested, rice straw was found most effective for the induction of xylanase that produced 4288.3 IU/gds of xylanase by S. commune ARC-11. Maximum xylanase production (6721.9 IU/gds) was observed on 8th day of incubation at temperature (30 °C), initial pH (7.0) and initial moisture content (70.0%). The supplementation of ammonium sulphate (0.08% N, as available nitrogen) enhanced the xylanase production up to 8591.4 IU/gds. The xylanase production by S. commune ARC-11 was further improved by the addition of 0.10%, (w/v) of Tween-20 as surfactant. The maximum xylanase activities were found at pH 5.0 and temperature 55 °C with a longer stability (180 min) at temperature 45, 50 and 55 °C. This xylanase preparation was also evaluated for the pre-bleaching of ethanol-soda pulp from Eulaliopsis binata. An enzyme dosage of 10 IU/g of xylanase resulted maximum decrease in kappa number (14.51%) with a maximum improvement 2.9% in ISO brightness compared to control.

20.
J Clin Diagn Res ; 11(4): XD01-XD03, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28571247

RESUMO

An Extramedullary Plasmacytoma (EMP) is characterized by a neoplastic proliferation of clonal plasma cells outside the medullary cavity. EMPs are a rare occurrence compared to other malignant plasma cell disorders and account for approximately 3-5% of plasma-cell neoplasms. Although most cases of EMP are not immediately life threatening at diagnosis, EMPs can progress to Multiple Myeloma (MM) and thus, warrant monitoring. Currently, there are no standard guidelines for when and how to monitor patients who are diagnosed with or treated for a solitary plasmacytoma. We present a case of solitary EMP who was treated adequately and definitively but developed a distinct, non-contiguous subsequent solitary EMP and was only discovered due to surveillance 18F-Fludeoxyglucose Positron Emission Tomography (18F-FDG) (PET) scan. Uniform surveillance guidelines should be developed and the potential benefits of PET and other imaging techniques as well as their cost should be considered.

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