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1.
Immunity ; 57(5): 1124-1140.e9, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38636522

RESUMEN

Signaling through Notch receptors intrinsically regulates tumor cell development and growth. Here, we studied the role of the Notch ligand Jagged2 on immune evasion in non-small cell lung cancer (NSCLC). Higher expression of JAG2 in NSCLC negatively correlated with survival. In NSCLC pre-clinical models, deletion of Jag2, but not Jag1, in cancer cells attenuated tumor growth and activated protective anti-tumor T cell responses. Jag2-/- lung tumors exhibited higher frequencies of macrophages that expressed immunostimulatory mediators and triggered T cell-dependent anti-tumor immunity. Mechanistically, Jag2 ablation promoted Nr4a-mediated induction of Notch ligands DLL1/4 on cancer cells. DLL1/4-initiated Notch1/2 signaling in macrophages induced the expression of transcription factor IRF4 and macrophage immunostimulatory functionality. IRF4 expression was required for the anti-tumor effects of Jag2 deletion in lung tumors. Antibody targeting of Jagged2 inhibited tumor growth and activated IRF4-driven macrophage-mediated anti-tumor immunity. Thus, Jagged2 orchestrates immunosuppressive systems in NSCLC that can be overcome to incite macrophage-mediated anti-tumor immunity.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Factores Reguladores del Interferón , Proteína Jagged-2 , Neoplasias Pulmonares , Ratones Noqueados , Macrófagos Asociados a Tumores , Proteína Jagged-2/metabolismo , Proteína Jagged-2/genética , Proteína Jagged-2/inmunología , Animales , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ratones , Humanos , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Transducción de Señal , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Línea Celular Tumoral , Ratones Endogámicos C57BL , Receptores Notch/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Escape del Tumor/inmunología
2.
Future Oncol ; : 1-11, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38629593

RESUMEN

Aim: To assess real-world clinical outcomes with standard therapies for advanced non-small-cell lung cancer (aNSCLC) with METexon14 skipping mutation (METex14). Methods: In an oncologists-led retrospective review of medical records, data were abstracted and analyzed for patients initiating first-line (1L) systemic therapy after 1 January 2017. Results: In total 287 aNSCLC patients with METex14, the real-world best overall response rate was 73.4% for capmatinib (n = 146), 68.8% for immunotherapy (IO) monotherapy (n = 48), 52.0% for chemotherapy (CT, n = 30), and 54.8% for IO + CT (n = 63). As compared with capmatinib, patients receiving IO (hazard ratio [HR]: 1.57; 95% CI: 0.77-3.20; p = 0.220), CT (HR: 2.41; 95% CI: 1.19-4.85; p = 0.014) and IO + CT (HR: 2.33; 95% CI: 1.35-4.04; p = 0.003) had higher rates of progression. Further, patients receiving CT (HR: 4.43; 95% CI: 1.54-12.75; p = 0.006) and IO + CT (HR: 3.53, 95% CI: 1.41-8.85; p = 0.007) had higher rates of mortality than patients receiving capmatinib. Conclusion: The study showed better clinical outcomes with capmatinib than other standard therapies in 1L setting for aNSCLC harboring METex14.


Real-world study that investigated the outcomes of different therapies used to treat non-small-cell lung cancer patients with mesenchymal-epithelial transition exon 14 skipping mutationWhat is this article about? A real-world study that investigated clinical outcomes in patients with diagnosis of advanced non-small-cell lung cancer (aNSCLC) with mesenchymal-epithelial transition exon 14 (METex14) skipping­a rare form of genetic mutation­who received treatment with one of the commonly used therapies for this disease: immunotherapy, chemotherapy, immunotherapy + chemotherapy combination and capmatinib, which is a highly selective inhibitor of MET tyrosine kinase protein involved in the growth of cancer cells.What were the results? The study showed that, in general, patients treated with capmatinib as the frontline therapy more frequently achieved a clinical response in the form of complete tumor resolution or tumor shrinkage, had a lower risk of disease worsening and lived longer than patients who were treated with immunotherapy, chemotherapy or immunotherapy + chemotherapy combination.What do the results of the study mean? This study suggests that capmatinib is effective in treating patients with aNSCLC with METex14 skipping who have not been treated with another anticancer therapy previously. It provides evidence to support the use of capmatinib in the frontline setting and may inform clinical decision-making in routine practice.

3.
Bioorg Chem ; 143: 107094, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199139

RESUMEN

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.


Asunto(s)
Antineoplásicos , Moduladores de Tubulina , Tubulina (Proteína) , Animales , Humanos , Ratones , Amidas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Microtúbulos/metabolismo , Mitosis , Tubulina (Proteína)/efectos de los fármacos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacología
4.
Cancer ; 129(2): 264-271, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36420773

RESUMEN

BACKGROUND: Immunotherapy using a checkpoint inhibitor (CPI) alone or in combination with chemotherapy is the standard of care for treatment-naive patients with advanced non-small cell lung cancer (NSCLC) without driver mutations for which targeted therapies have been approved. It is unknown whether continuing CPI treatment beyond disease progression results in improved outcomes. METHODS: Patients who experienced progressive disease (PD) after a clinical benefit from chemotherapy plus a CPI were enrolled. Patients received pembrolizumab (200 mg every 3 weeks) plus next-line chemotherapy. The primary end point was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary end points included the overall survival (OS), clinical benefit rate, and toxicity. The authors' hypothesis was that continuing pembrolizumab beyond progression would improve the median PFS to 6 months in comparison with a historical control of 3 months with single-agent chemotherapy alone. RESULTS: Between May 2017 and February 2020, 35 patients were enrolled. The patient and disease characteristics were as follows: 51.4% were male; 82.9% were current or former smokers; and 74.3%, 20%, and 5.7% had adenocarcinoma, squamous cell carcinoma, and NSCLC not otherwise specified, respectively. The null hypothesis that the median PFS would be 3 months was rejected (p < .05). The median PFS was 5.1 months (95% confidence interval [CI], 3.6-8.0 months). The median OS was 24.5 months (95% CI, 15.6-30.9 months). The most common treatment-related adverse events were fatigue (60%), anemia (54.3%), and nausea (42.9%). There were no treatment-related deaths. CONCLUSIONS: Pembrolizumab plus next-line chemotherapy in patients with advanced NSCLC who experienced PD after a clinical benefit from a CPI was associated with statistically significant higher PFS in comparison with historical controls of single-agent chemotherapy alone.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
5.
Echocardiography ; 40(8): 879-883, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37392399

RESUMEN

A 16-year-old male with past medical history of congenital atrial septal defect surgical repair, presented with recurrent pericarditis secondary to post-cardiotomy injury syndrome (PCIS), After failing medical therapy, he ultimately underwent pericardiectomy for symptom resolution, PCIS is underdiagnosed in children and should be considered in patients with recurrent chest, pain.


Asunto(s)
Lesiones Cardíacas , Defectos del Tabique Interatrial , Pericarditis Constrictiva , Pericarditis , Masculino , Niño , Humanos , Adolescente , Pericarditis Constrictiva/diagnóstico , Pericarditis/complicaciones , Pericardiectomía , Síndrome , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/cirugía , Lesiones Cardíacas/diagnóstico por imagen , Lesiones Cardíacas/etiología , Lesiones Cardíacas/cirugía
6.
Molecules ; 28(15)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37570887

RESUMEN

Making nanoscale drug carriers could boost the bioavailability of medications that are slightly water soluble. One of the most promising approaches for enhancing the chemical stability and bioavailability of a variety of therapeutic medicines is liquid nanocrystal technology. This study aimed to prepare nanocrystals of mangiferin for sustained drug delivery and enhance the pharmacokinetic profile of the drug. The fractional factorial design (FFD) was used via a selection of independent and dependent variables. The selected factors were the concentration of mangiferin (A), hydroxypropyl methyl cellulose (HPMC) (B), pluronic acid (C), tween 80 (D), and the ratio of antisolvent to solvent (E). The selected responses were the particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The nanocrystals were further evaluated for mangiferin release, release kinetics, Fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential, and scanning electron microscopy (SEM). The stability studies of developed nanocrystals were performed for 6 months and pharmacokinetics on albino rabbits. The value of entrapment efficiencies ranged from 23.98% to 86.23%. The percentage release of mangiferin varied from 62.45 to 99.02%. FTIR and DSC studies showed the stability of mangiferin in the nanocrystals. The particle size of the optimized formulation was almost 100 nm and -12 mV the value of the zeta potential. The results of stability studies showed that the nanocrystals of mangiferin were stable for a period of six months. The peak plasma concentration of mangiferin from nanocrystals and suspension of mangiferin were 412 and 367 ng/mL, respectively. The value of AUC0-t of nanocrystals and suspension of mangiferin was 23,567.45 ± 10.876 and 18,976.12 ± 9.765 µg×h/mL, respectively, indicating that the nanocrystals of mangiferin showed greater availability of mangiferin compared to the suspension of the formulation. The developed nanocrystals showed a good release pattern of mangiferin, better stability studies, and enhanced the pharmacokinetics of the drug.

7.
AAPS PharmSciTech ; 24(2): 55, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36759413

RESUMEN

The study aims to determine histamine efficacy on hematologic values in experimental animal model, under physiological and pathological conditions after inducing diphenhydramine-formulated nasal nano-gel/nano-emulgel in comparison with conventional nasal spray regime. In this study, we conducted experiment on New Zealand white male rabbits to prove our hypothesis that nasal diphenhydramine nano-gel and nano-emulgel can penetrate the nasal mucosa faster to show drug response and subside histaminic symptoms than market nasal spray (as reference). Blood samples from 48 New Zealand white male rabbits, under both experimental conditions (physiological and pathological) divided into four groups for each (n = 6) were investigated after inducing each dosage form intranasally. Hematologic parameters (WBCs, RBCs, HGB, PLTs, lymphocytes, monocytes, eosinophils, granulocyte counts) were analyzed in whole blood samples, collected at different time intervals. ANOVA and completely randomized design (CRD) were applied for statistical analysis. Histopathologically, nasal tissues of all groups were analyzed to see intramucosal surface changes. Data of descriptive statistics of hematological parameters analyzed at confidence level 95% showed that under physiological condition, hematological parameters of all groups were lying in normal range, whereas under pathological condition, low values of all hematological parameters were observed in all groups due to allergenic condition. The groups B (allergenic rabbits treated with formulated diphenhydramine nasal nano-gel) and C (allergenic rabbits treated with formulated diphenhydramine nasal nano-emulgel) have shown good changes in the treatment of allergenic rabbits as compared to group D (allergenic rabbits treated with formulated diphenhydramine nasal spray). The completely randomized ANOVA and Tukey HSD all-pairwise comparison tests of hematological parameters were applied that showed all groups in both studies were significantly different from each other. It was observed after histopathological study of nasal membrane tissues that change in mucosa has occurred due to the passage of drug. In summary, hematological profile and histopathological study have demonstrated the comparable results with conventional diphenhydramine nasal spray and formulated diphenhydramine nasal nano-gel/nano-emulgel which can exhibit considerable drug delivery dosage forms in the management of allergic rhinitis in animal model.


Asunto(s)
Difenhidramina , Rinitis Alérgica , Masculino , Animales , Conejos , Administración Intranasal , Rociadores Nasales , Rinitis Alérgica/tratamiento farmacológico , Mucosa Nasal , Alérgenos , Modelos Animales
8.
J Nat Prod ; 85(6): 1503-1513, 2022 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-35687347

RESUMEN

Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin (11), potently inhibited the proliferation of various cancer cell lines with IC50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 µM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery endeavors.


Asunto(s)
Aurora Quinasa A , Aurora Quinasa B , Neoplasias , Inhibidores de Proteínas Quinasas , Quinonas , Antraquinonas , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa B/antagonistas & inhibidores , Línea Celular Tumoral , ADN Helicasas , Humanos , Proteínas Nucleares , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Quinonas/química , Quinonas/farmacología , Factores de Transcripción
9.
Curr Cardiol Rep ; 24(12): 2031-2041, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36441403

RESUMEN

PURPOSE OF REVIEW: To review myocarditis and pericarditis developing after COVID-19 vaccinations and identify the management strategies. RECENT FINDINGS: COVID-19 mRNA vaccines are safe and effective. Systemic side effects of the vaccines are usually mild and transient. The incidence of acute myocarditis/pericarditis following COVID-19 vaccination is extremely low and ranges 2-20 per 100,000. The absolute number of myocarditis events is 1-10 per million after COVID-19 vaccination as compared to 40 per million after a COVID-19 infection. Higher rates are reported for pericarditis and myocarditis in COVID-19 infection as compared to COVID-19 vaccines. COVID-19 vaccine-related inflammatory heart conditions are transient and self-limiting in most cases. Patients present with chest pain, shortness of breath, and fever. Most patients have elevated cardiac enzymes and diffuse ST-segment elevation on electrocardiogram. Presence of myocardial edema on T2 mapping and evidence of late gadolinium enhancement on cardiac magnetic resonance imaging are also helpful additional findings. Patients were treated with non-steroidal anti-inflammatory drugs and colchicine with corticosteroids reserved for refractory cases. At least 3-6 months of exercise abstinence is recommended in athletes diagnosed with vaccine-related myocarditis. COVID-19 vaccination is recommended in all age groups for the overall benefits of preventing hospitalizations and severe COVID-19 infection sequela.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Miocarditis , Pericarditis , Humanos , Medios de Contraste , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Gadolinio , Inflamación , Miocarditis/inducido químicamente , Pericarditis/inducido químicamente , Pericardio/fisiopatología
10.
Br J Cancer ; 125(7): 966-974, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34446858

RESUMEN

BACKGROUND: Activating mutations in the Fms-like tyrosine kinase 3 (FLT3) are among the most prevalent oncogenic mutations in acute myeloid leukaemia. Inhibitors selectively targeting FLT3 kinase have shown promising clinical activity; their success in the clinic, however, has been limited due to the emergence of acquired resistance. METHODS: CCT245718 was identified and characterised as a dual Aurora A/FLT3 inhibitor through cell-based and biochemical assays. The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to FLT3 inhibitors. RESULTS: CCT245718 exhibits potent antiproliferative activity towards FLT3-ITD + AML cell lines and strongly binds to FLT3-ITD and TKD (D835Y) mutants in vitro. Activities of both FLT3-ITD and Aurora A are also inhibited in cells. Inhibition of FLT3 results in reduced phosphorylation of STAT5, downregulation of survivin and induction of apoptotic cell death. Moreover, CCT245718 overcomes TKD-mediated resistance in a MOLM-13-derived cell line containing FLT3 with both ITD and D835Y mutations. It also inhibits FLT3 signalling in both parental and resistant cell lines compared to FLT3-specific inhibitor MLN518, which is only active in the parental cell line. CONCLUSIONS: Our results demonstrate that CCT245718 is a potent dual FLT3/Aurora A inhibitor that can overcome TKD-mediated acquired resistance.


Asunto(s)
Aurora Quinasa A/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Imidazoles/farmacología , Leucemia Mieloide Aguda/enzimología , Tirosina Quinasa 3 Similar a fms/genética , Aurora Quinasa A/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/química , Leucemia Mieloide Aguda/tratamiento farmacológico , Mutación , Fosforilación , Proteínas Recombinantes/farmacología , Factor de Transcripción STAT5/metabolismo , Survivin/metabolismo , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Tirosina Quinasa 3 Similar a fms/química
11.
BMC Cancer ; 21(1): 808, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34256732

RESUMEN

BACKGROUND: Though the gut microbiome has been associated with efficacy of immunotherapy (ICI) in certain cancers, similar findings have not been identified for microbiomes from other body sites and their correlation to treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs. METHODS: We designed a prospective cohort study conducted from 2018 to 2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Patients with histopathologically confirmed, advanced/metastatic LC planned to undergo immunotherapy-based treatment were enrolled between September 2018 and June 2019. Nasal, buccal and gut microbiome samples were obtained prior to initiation of immunotherapy +/- chemotherapy, at development of adverse events (irAEs), and at improvement of irAEs to grade 1 or less. RESULTS: Thirty-seven patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium (p = 0.001) and Desulfovibrio (p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales (p = 0.018) but reduced Rikenellaceae (p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. CONCLUSIONS: This pilot study identifies significant differences in the gut microbiome between HC and LC patients, and their correlation to treatment response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688347 . Retrospectively registered 09/28/2018.


Asunto(s)
Microbioma Gastrointestinal/fisiología , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos
12.
Echocardiography ; 38(6): 1077-1080, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33929773

RESUMEN

The presence of human coronavirus HKU1 infection associated with pericardial inflammation is not reported. We are reporting a young woman with systemic lupus erythematosus, who was positive for HKU1 during her pericarditis flare. Diagnostic imaging demonstrated pericardial effusion, edema, and late gadolinium enhancement on cardiac magnetic resonance imaging and echocardiography. She was on multiple anti-inflammatory medications and achieved remission with anakinra. Her management and a brief literature review is also presented.


Asunto(s)
Coronavirus , Lupus Eritematoso Sistémico , Pericarditis , Medios de Contraste , Femenino , Gadolinio , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pericarditis/complicaciones , Pericarditis/diagnóstico
13.
Curr Cardiol Rep ; 23(7): 90, 2021 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-34081219

RESUMEN

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID19) involves the heart, including pericardium. This article reviews the possible pathophysiological mechanisms in pericardial involvement in COVID19 and pericardial manifestations of COVID19. It also summarizes the patients with pericarditis secondary to COVID19 and outlines the contemporary treatment strategies in this patient population. RECENT FINDINGS: A high degree of suspicion is required to identify the pericardial involvement in COVID19 patients. It is proposed that an underlying hyperinflammatory reaction in COVID19 leads to pericardial inflammation. Acute pericarditis with or without myocardial involvement is diagnosed on clinical presentation, serum inflammatory markers, electrocardiogram, and echocardiogram. Multimodality imaging may also have an additional diagnostic value. Patients are usually managed medically, but some patients develop a life-threatening pericardial tamponade necessitating pericardial drainage. Pericardial involvement is an important clinical manifestation of COVID19 requiring a proper workup. Timely diagnosis and a specific management plan based on the presentation and concomitant organ involvement usually lead to a complete recovery.


Asunto(s)
COVID-19 , Taponamiento Cardíaco , Derrame Pericárdico , Pericarditis , Taponamiento Cardíaco/diagnóstico por imagen , Taponamiento Cardíaco/etiología , Humanos , Pericarditis/diagnóstico por imagen , Pericarditis/terapia , Pericardio/diagnóstico por imagen , SARS-CoV-2
14.
Curr Cardiol Rep ; 22(10): 127, 2020 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32856192

RESUMEN

PURPOSE OF REVIEW: Pericarditis secondary to acute myocardial infarction (AMI) is known to develop either immediately or after a latent period of few months. Due to varied presentation and timing, its diagnosis and treatment can be challenging. This article reviews underlying mechanisms and the role of cardiac imaging in investigating and managing this condition. RECENT FINDINGS: Timely diagnosis of pericarditis after AMI is important to prevent potential progression to complicated pericarditis. Clinical suspicion warrants initial investigation with serum inflammatory levels, electrocardiogram, and echocardiography. When findings are inconclusive, cardiac magnetic resonance imaging and computerized tomography can provide additional diagnostic information. Pericarditis after AMI is a treatable condition. Clinicians should maintain a high suspicion in this era of revascularization and develop a strategic plan for timely diagnosis and management.


Asunto(s)
Lesiones Cardíacas , Infarto del Miocardio , Pericarditis , Ecocardiografía , Electrocardiografía , Humanos , Infarto del Miocardio/complicaciones , Pericarditis/etiología
16.
J Relig Health ; 58(5): 1833-1846, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31230162

RESUMEN

Effective communication between intensive care unit (ICU) staff, and patients and their families, can help increase understanding, trust, and goals-of-care decisions. Many strategies focus on enhancing communication by increasing family meetings or adding patient navigators. In our ICU, we implemented both strategies, uniquely appointing a chaplain for the patient navigator role. We then surveyed ICU staff on their perceptions of the chaplain/patient navigator, which yielded several valuable insights. Although all staff supported a strong chaplaincy presence, many had concerns about the dual chaplain/patient navigator role. Based on our mixed results, we encourage further exploration to optimize the chaplain role in the ICU.


Asunto(s)
Clero/psicología , Unidades de Cuidados Intensivos/organización & administración , Defensa del Paciente , Navegación de Pacientes , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Familia , Humanos , Persona de Mediana Edad , Mejoramiento de la Calidad
18.
AAPS PharmSciTech ; 19(4): 1730-1743, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29569155

RESUMEN

The aim of present study is to formulate diphenhydramine nasal nano-emulgels, having lipophilic nano-sized interior droplets, with better penetration for targeted controlled delivery to mucous membrane. Different diphenhydramine (DPH) nasal nano-emulgels were developed having propylene glycol and olive oil (as permeation enhancers) by using RSM for optimization and then evaluated for physico-chemical characteristics and thermal stability. In-vitro drug release through cellophane membrane was conducted and results were analyzed statistically. Further, gelation, mucoadhesive stress, and ex-vivo and histopathological studies were performed on optimized formulation by using goat nasal membrane. Among all formulations, E2 showed maximum DPH release at higher concentration olive oil (4%) and lower concentration propylene glycol (PG) (25%) within 4 h. All formulations have followed first-order kinetics and drug release mechanism was Fickian diffusion. Analysis of variance (ANOVA) and multiple linear regression analysis (MLRA) were used to compare results among formulations and 3D surface plots were constructed also. Optimized formulation showed immediate prolong gelation in artificial nasal mucosa and excellent mucoadhesive property (72.5 ± 1.5 dynes/cm2). Approximately 97.1% optimized formulation was permeated through membrane within 4 h, having a high flux rate (33.19 ± 0.897 µg/cm2/min) with diffusion coefficient (0.000786 ± 4.56 × 10-5 cm2/min) while drug contents remained on mucosal membrane for 24 h. Histopathologically, change on intra-mucosal surface of excised membrane was observed due to passage of drug through it. In summary, combination of PG and olive oil in nasal DPH nano-emulgel can be utilized successfully for targeted controlled delivery. The optimized formulation has excellent permeability and prolonged residence time on mucosal surface, which prove its good anti-histaminic activity in case of allergic rhinitis.


Asunto(s)
Difenhidramina/administración & dosificación , Difenhidramina/metabolismo , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Animales , Difenhidramina/química , Composición de Medicamentos , Sistemas de Liberación de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/métodos , Liberación de Fármacos , Geles , Cabras , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/química , Antagonistas de los Receptores Histamínicos H1/metabolismo , Humanos , Aceite de Oliva/administración & dosificación , Aceite de Oliva/química , Aceite de Oliva/metabolismo , Permeabilidad , Propilenglicol/administración & dosificación , Propilenglicol/química , Propilenglicol/metabolismo
19.
Biotechnol Lett ; 39(10): 1441-1451, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28726080

RESUMEN

Seeds play essential roles in plant life cycle and germination is a complex process which is associated with different phases of water imbibition. Upon imbibition, seeds begin utilization of storage substances coupled with metabolic activity and biosynthesis of new proteins. Regeneration of organelles and emergence of radicals lead to the establishment of seedlings. All these activities are regulated in coordinated manners. Translation is the requirement of germination of seeds via involvements of several proteins like beta-amylase, starch phosphorylase. Some important proteins involved in seed germination are discussed in this review. In the past decade, several proteomic studies regarding seed germination of various species such as rice, Arabidopsis have been conducted. We face A paucity of proteomic data with respect to woody plants e.g. Fagus, Pheonix etc. With particular reference to Cyclobalnopsis gilva, a woody plant having low seed germination rate, no proteomic studies have been conducted. The review aims to reveal the complex seed germination mechanisms from woody and herbaceous plants that will help in understanding different seed germination phases and the involved proteins in C. gilva.


Asunto(s)
Proteínas de Plantas/metabolismo , Proteómica/métodos , Quercus/fisiología , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Germinación , Quercus/metabolismo
20.
J Pak Med Assoc ; 67(11): 1747-1750, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29171573

RESUMEN

Puberty heralds the onset of adulthood, and is fraught with complex physiological and psychological changes and emotions. In this study, we looked at the sources of information about puberty and sex education among males and females, age at which they learned about them, and the opinions on the role of schools and parents in imparting this education among medical students.A cross-sectional pilot study, using convenience sampling was conducted among 153 medical students of the Hamdard College of Medicine and Dentistry (HCM&D) in Karachi. Regarding most common source of information about puberty; 23 (25.3%) males identified friends as the most important source of information. While 31 (50.0%) women identified their mothers as the most important source.Regarding most common source of information about reproductive systems and sex; 17 (27.4%) women identified school teachers as the most common source of information, while 26 (28.6%) men identified books and magazines.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Educación Sexual , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Pakistán/epidemiología , Educación Sexual/métodos , Educación Sexual/estadística & datos numéricos , Adulto Joven
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