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2.
Int J Immunopathol Pharmacol ; 38: 3946320241274255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39122243

RESUMEN

OBJECTIVES: Human endogenous retroviruses (HERVs) are integral components of the human genome, and their reactivation has been implicated in the pathogenesis of some malignancies. External viral co-infections are suspected to play a role in HERV transactivation. This study aimed to investigate the expression of HERV-K np9 elements and HERV-R env gene in pediatric acute lymphoblastic leukemia (ALL) patients. Additionally, we explored potential correlations between HERV expression and common viral infections prevalent in this group of patients. METHODS: Blood samples were collected from 43 pediatric ALL patients and 48 age- and sex-matched healthy controls. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of HERV-K np9 and HERV-R env, along with herpes simplex virus (HSV), parvovirus B19, and polyomavirus BK. RESULTS: HERV-K np9 and HERV-R env showed significantly higher expression in the peripheral blood of ALL patients compared to healthy controls (p < .001 and p = .003, respectively). HSV positivity was associated with significantly increased HERV-K np9 expression. No significant correlations were observed between other investigated viruses and HERV gene expression. CONCLUSION: The overexpression of HERV-K np9 and HERV-R env in pediatric ALL patients suggest their potential role in leukemogenesis. Our findings also suggest a possible link between HSV infection and HERV reactivation in this population. Future investigations are needed to understand the precise roles of these genes and viral infections in the development of ALL.


Asunto(s)
Retrovirus Endógenos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Retrovirus Endógenos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Masculino , Femenino , Niño , Preescolar , Productos del Gen env/genética , Productos del Gen env/metabolismo , Adolescente , Estudios de Casos y Controles
3.
Tissue Eng Part A ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135398

RESUMEN

Biomaterials often have subtle properties that ultimately drive their bespoke performance. Given this nuanced structure-function behavior, the standard scientific approach of one experiment at a time or design of experiment (DOE) methods is largely inefficient for the discovery of complex biomaterials. More recently, high-throughput experimentation coupled with machine learning methods have matured beyond expert users allowing scientists and engineers from diverse backgrounds to access these powerful data science tools. As a result, we now have the opportunity to strategically utilize all available data from high- throughput experiments to train efficacious models and map the structure-function behavior of biomaterials for their discovery. Herein, we discuss this necessary shift to data-driven determination of structure-function properties of biomaterials as we highlight how machine learning is leveraged in identifying physicochemical cues for biomaterials in tissue engineering, gene delivery, drug delivery, protein stabilization, and antifouling materials. We also discuss data-mining approaches that are coupled with machine learning to map biomaterial functions that reduce the load on experimental approaches for faster biomaterial discovery. Ultimately, harnessing the prowess of machine learning will lead to accelerated discovery and development of optimal biomaterial designs.

4.
BMC Med Educ ; 24(1): 929, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187814

RESUMEN

BACKGROUND: Socioeconomic status (SES) is a social classification factor that takes into account income, parental education and occupation. SES has been shown to play an important role in shaping students' academic performance, including in medical schools, but there still remains significant variation in findings around SES and academic achievement worldwide. We aim to assess and explore socioeconomic disparities and their effects on medical school performance at Sudanese public and private universities. OBJECTIVES: The objective of our study was to assess the effects of age, sex, living conditions, parental education and income level on the academic achievement of medical students from universities in Sudan. METHODS: This cross-sectional study was conducted among undergraduate medical students at ten public universities in Sudan between September and December 2023. Participants were included if they were older than 18 years and were studying in their 2nd year or older. The data were collected using an online questionnaire with open- and closed-ended questions measuring age, living conditions, parental income level and education. A convenience sampling method was used to recruit participants from universities. The data were analyzed using SPSS v28.0.0, and a p value less than 0.05 was used to indicate statistical significance. RESULTS: We received 832 responses, 516 (62%) from females and 307 (36.9%) from males. The median age was 23 years. Most students lived with their families (61.1%), followed by student housing (28.2%). This study revealed age (p = .024) (95% Cl: 0.025- 0.023) andhigh family income (p = .019) (95% Cl: 0.018- 0.02) are associated with academic achievement in the long term, as demonstrated through cumulative grade point average (cGPA). CONCLUSION: The findings underscore the importance of targeted support systems to bridge the socioeconomic gaps that exist among medical students, allowing all students to thrive academically regardless of their background. CLINICAL TRIAL NUMBER: None.


Asunto(s)
Éxito Académico , Estudiantes de Medicina , Humanos , Sudán , Femenino , Masculino , Estudios Transversales , Estudiantes de Medicina/estadística & datos numéricos , Adulto Joven , Adulto , Universidades , Factores Socioeconómicos , Clase Social , Encuestas y Cuestionarios , Educación de Pregrado en Medicina , Facultades de Medicina , Disparidades Socioeconómicas en Salud
5.
Bioorg Chem ; 150: 107623, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39002251

RESUMEN

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1ß. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.


Asunto(s)
Antiinflamatorios no Esteroideos , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Simulación del Acoplamiento Molecular , Piridazinas , Piridazinas/farmacología , Piridazinas/química , Piridazinas/síntesis química , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Animales , Ciclooxigenasa 2/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Humanos , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/inducido químicamente , Ratas , Masculino , Ciclooxigenasa 1/metabolismo , Ratones
6.
RSC Adv ; 14(31): 22434-22448, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39010911

RESUMEN

Aminopeptidase N (APN) is regarded as an attractive target for cancer treatment due to its overexpression in various types of malignancies and its close association with cancer angiogenesis, metastasis and invasion. Herein the authors describe the design, synthesis and biological evaluation of some naturally based pyrazoline derivatives. Among these compounds, the diphenylpyrazole carbothioamide 8 showed significant activity and selectivity index (SI = 4.7) on breast (MCF-7) human cancer cell line and was capable of inhibiting APN with pIC50 value of 4.8, comparable to the reference standard. Further evaluation of derivative 8 against VEGFR2 and MMP9 as biomarkers for angiogenesis and invasion showed that the selected compound had an inhibitory activity on both proteins with pIC50 values of 6.7 and 6.4, respectively. Additionally, the migration ability of cells following treatment with the diphenylpyrazole derivative decreased to record a percentage wound closure of 57.77 for compound 8versus 97.03 for the control. The promising derivative arrested cell growth at the G1 phase inducing early and late apoptosis. Finally, docking and ADMET in silico studies were performed.

7.
Int J Biol Macromol ; 272(Pt 2): 132864, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38844272

RESUMEN

Scleroglucan is a notable member of the ß-glucan microbial polysaccharides with a long tradition of industrial and therapeutic use. The local strain, previously identified as Athelia rolfsii TEMG MH 236106 produced an appreciable amount of scleroglucan using glucose as a carbon source and yeast extract as a nitrogen source. Plackett-Burman design was employed to effectively screen critical medium composition, culture, and fermentation conditions. Athelia rolfsii TEMG MH 236106 produced the maximum amount of scleroglucan (18.12 g/L) with a 45.3 % glucose conversion. Out of the eleven variables, the most effective factors showing a high level of significance are as follows: glucose, yeast extract, citric acid, inoculum disc numbers, culture volume and incubation time. An update to maximize scleroglucan production in the central composite design for four parameters (glucose and yeast extract concentrations, disc number, medium volume and incubation time) with 31 runs was applied and the production of scleroglucan reached its maximum at 31.56 g/L with 78.9 % glucose conversion. Three models of Sclg-5-fluorouracil complexes have been employed to study in vitro drug release investigations. Hence, the Sclg-5-FU (5 and 10 mg/mL) models appeared to be the most suitable for drug administration due to their concentration and distribution within capsules.


Asunto(s)
Fluorouracilo , Glucanos , Glucanos/química , Fluorouracilo/farmacología , Fluorouracilo/metabolismo , Fermentación , Liberación de Fármacos , Glucosa/metabolismo , Medios de Cultivo/química
8.
Artículo en Inglés | MEDLINE | ID: mdl-38905720

RESUMEN

Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine.


Asunto(s)
Decitabina , Espectrometría de Masas en Tándem , Animales , Espectrometría de Masas en Tándem/métodos , Decitabina/farmacocinética , Decitabina/sangre , Decitabina/administración & dosificación , Ratones , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Azacitidina/farmacocinética , Azacitidina/sangre , Azacitidina/análogos & derivados , Azacitidina/administración & dosificación , Azacitidina/química , Modelos Lineales , Uridina/farmacocinética , Uridina/sangre , Uridina/análogos & derivados , Sensibilidad y Especificidad , Límite de Detección
9.
PLoS One ; 19(6): e0304980, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38905247

RESUMEN

BACKGROUND: Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied. OBJECTIVES: In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT). METHODS: Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells. RESULTS: No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed. CONCLUSION: This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance.


Asunto(s)
Escherichia coli , Transferencia de Gen Horizontal , Plásmidos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Plásmidos/genética , Metoclopramida/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Conjugación Genética , Farmacorresistencia Microbiana/genética , Farmacorresistencia Microbiana/efectos de los fármacos
10.
Int Immunopharmacol ; 137: 112465, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38878489

RESUMEN

INTRODUCTION: Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals. AIM: This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated. METHOD: Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA. RESULTS: Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1ß. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death. CONCLUSION: This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.


Asunto(s)
Ácido Acético , Adenosina Monofosfato , Alanina , Antiinflamatorios , Colitis Ulcerosa , Colon , Citocinas , Piroptosis , Sirtuinas , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Piroptosis/efectos de los fármacos , Ratas , Masculino , Colon/patología , Colon/efectos de los fármacos , Colon/inmunología , Sirtuinas/metabolismo , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/farmacología , Citocinas/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Guanosina Monofosfato , Humanos
11.
Clin Exp Reprod Med ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38853129

RESUMEN

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs. Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels. Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

12.
Health Sci Rep ; 7(5): e882, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736478

RESUMEN

Background: Etrolizumab is a promising drug for treating moderate to severe ulcerative colitis. Aim: The aim of this study was to assess the efficacy and safety of etrolizumab for induction and maintenance of remission in moderate to severe ulcerative colitis. Methods: We searched the following databases: PUBMED, Web of Science, OVID, and SCOPUS from inception to January 15. Inclusion criteria were any phase 2 and 3 clinical trials that compared etrolizumab with a placebo in treating moderate to severe ulcerative colitis, excluding case reports, animal studies, phase 1 trials, and conference abstracts due to duplication. We used RevMan software (5.4) for the meta-analysis. Results: Five clinical trials were included in our meta-analysis. The total number of patients included in the study is 1248 patients, 860 patients in the etrolizumab group and 388 patients in the placebo group. In the induction phase, the pooled analyses showed a statistically significant association between etrolizumab and increased clinical remission, and endoscopic remission compared with placebo (risk ratio [RR] = 2.66, 95% confidence interval [CI] = 1.69-4.19, p < 0.0001), and (RR = 2.35, 95% CI = 1.52-3.65, p = 0.0001), respectively. In the maintenance phase, the pooled analyses showed a statistically significant association between etrolizumab and increased histologic remission and endoscopic remission (RR = 2.04, 95% CI = 1.40-2.98, p = 0.0002) and (RR = 1.92, 95% CI = 1.29-2.85, p = 0.001), respectively. No statistically significant difference was observed in adverse events between etrolizumab and placebo in the induction and maintenance phases. Conclusion: Our results show that etrolizumab is an effective and safe drug for the induction and maintenance of clinical remission in moderate to severe ulcerative colitis patients, as proved by histologic and endoscopic findings. Future randomized trials are still needed to compare etrolizumab to the other agents and further establish its value for the practice.

13.
Cureus ; 16(4): e58694, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38774167

RESUMEN

In this narrative review, we explore the relationship between long COVID patients and their risk of developing heart failure (HF). Patients with long COVID face a heightened risk of HF, a critical cardiovascular complication linked to the prolonged effects of COVID-19. Clinical manifestations of long COVID-associated HF present diagnostic challenges, complicating patient management. Multidisciplinary care is essential to address these complexities effectively. We found that long COVID can result in various cardiovascular issues including HF. The current view is long COVID leads to HF by activating systemic inflammation by causing endothelial dysfunction, which leads to activation of the complement pathways, tissue factor pathways, and Von Willebrand factor; activation of all these factors leads to venous and arterial thrombosis, which could lead to clogging of blood vessel of the heart leading to cardiovascular complications. The association between long COVID and HF can be challenging despite being recognized as comorbidity because biomarkers are not dependable in determining whether a patient had HF before or after contracting COVID-19. Emerging therapeutic modalities offer hope for improving outcomes, but further research is needed to refine management strategies and mitigate long-term cardiovascular consequences of COVID-19.

14.
Poult Sci ; 103(7): 103746, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38678974

RESUMEN

Polyunsaturated fatty acids (PUFA), including n-6 and n-3 fatty acids, are essential for enhancing the performance and health of poultry. Avian species lack desaturase enzymes for endogenous synthesis of n-6 and n-3 fatty acids. This work aimed to determine the impacts of including soybean oil (SO) and linseed oil (LO) in quail diets on growth, lipid profile, hepatic and renal functions, immunity, and antioxidant status. A total of 350 Japanese quail chicks (1-wk-old) were randomly arranged into 7 dietary treatment groups. Seven isocaloric and isonitrogenous experimental basal diets were formed based on the nutritional requirements of growing Japanese quail. Group 1, the control, received a basal with no oils, while groups 2 to 7 received a basal diet containing either 1% SO, 1.5% SO, 2% SO, 1% LO, 1.5% LO, or 2% LO, respectively. Quail groups that consumed diets containing LO at all levels showed significantly greater live body weight (LBW) at 5th wk of age than other experimental groups. The dietary incorporation of 1.5 or 2% SO or LO at all levels yielded significant improvements in body weight gain (BWG) and feed conversion ratio (FCR) through 3 to 5 and 1 to 5 wk of age. Different dietary oil sources and levels have no significant impacts on feed intake (FI) and carcass yield parameters. Lipid profile parameters were improved by adding SO and LO in quail diets, with LO having a higher effect than SO. The hepatic and renal functionality were improved by adding SO and LO in quail diets. The lowest uric acid (UA) bloodstream concentrations were recorded in the quail group fed a diet with 2% LO. Values of Gamma globulins (G-GLO) and immunoglobulins (G, M, and A) were increased by adding SO or LO to quail diets. Blood levels of MDA and TAC were improved significantly by including LO in quail diets. The activity of the superoxide dismutase (SOD) enzyme was significantly increased by adding SO or LO to quail diets. Generally, adding SO or LO to growing quail diets up to 2% could yield favorable effects on growth performance, blood lipids, hepatic and renal functions, immunity, and antioxidant status; however, LO seems to have better effects than SO.


Asunto(s)
Alimentación Animal , Coturnix , Dieta , Suplementos Dietéticos , Aceite de Linaza , Aceite de Soja , Animales , Aceite de Linaza/administración & dosificación , Alimentación Animal/análisis , Dieta/veterinaria , Coturnix/crecimiento & desarrollo , Coturnix/fisiología , Aceite de Soja/administración & dosificación , Aceite de Soja/metabolismo , Suplementos Dietéticos/análisis , Distribución Aleatoria , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Masculino , Relación Dosis-Respuesta a Droga , Estado de Salud
15.
Artículo en Inglés | MEDLINE | ID: mdl-38636136

RESUMEN

A liquid chromatography - electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the quantification of letrozole, a third-generation aromatase inhibitor, and its main carbinol metabolite (CM) in support of murine pharmacokinetic studies. Using polarity switching, simultaneous ESI-MS measurement of letrozole and CM was achieved in positive and negative mode, respectively. The assay procedure involved a one-step protein precipitation and extraction of all analytes from mouse plasma requiring only 5 µL of sample. Separation was optimized on an Accucore aQ column with gradient elution at a flow rate of 0.4 mL/min in 5 min. Two calibration curves per day over four consecutive measurement days showed satisfactory linear responses (r2 > 0.99) over concentration ranges of 5-1000 ng/mL and 20-2000 ng/mL for letrozole and CM, respectively. No matrix effect was found, and the mean extraction recoveries were 103-108 % for letrozole and 99.8-107 % for CM. Precision and accuracy within a single run and over four consecutive measurement days were verified to be within acceptable limits. Application of the developed method to preclinical pharmacokinetic studies in mice receiving oral letrozole at a dose 1 or 10 mg/kg revealed that the systemic exposure to letrozole was dose-, formulation-, and strain-dependent. These findings may inform the future design of preclinical studies aimed at refining the pharmacological profile of this clinically important drug.


Asunto(s)
Inhibidores de la Aromatasa , Letrozol , Nitrilos , Espectrometría de Masas en Tándem , Triazoles , Animales , Letrozol/sangre , Letrozol/farmacocinética , Letrozol/química , Ratones , Espectrometría de Masas en Tándem/métodos , Inhibidores de la Aromatasa/sangre , Inhibidores de la Aromatasa/farmacocinética , Inhibidores de la Aromatasa/química , Cromatografía Líquida de Alta Presión/métodos , Nitrilos/sangre , Nitrilos/farmacocinética , Triazoles/sangre , Triazoles/farmacocinética , Triazoles/química , Reproducibilidad de los Resultados , Modelos Lineales , Límite de Detección , Femenino , Masculino
16.
Cureus ; 16(3): e56662, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38646224

RESUMEN

A myocardial diverticulum is a rare congenital anomaly characterized by pouch-like protrusions within the myocardial wall, which can potentially lead to various cardiac complications. This case report describes a unique presentation of a left ventricular diverticulum (LVD) with an associated apical thrombus, highlighting the diagnostic and management challenges posed by this condition. A 58-year-old man presented to the emergency department with left arm weakness, wrist drop, and chest pain, initially raising concerns for a stroke. Diagnostic evaluations, including echocardiography and magnetic resonance imaging (MRI), revealed a small focal outpouching at the left ventricular apex, consistent with a congenital LVD containing a thrombus. This diagnosis was supported by the patient's historical imaging dating back to 2007, which had similarly identified this outpouching. The patient was managed with anticoagulation therapy, transitioning from heparin to warfarin, alongside standard cardiac care. This case underscores the importance of considering myocardial diverticulum in the differential diagnosis of patients presenting with cardiac symptoms that might initially suggest more common conditions, such as stroke. It also highlights the essential role of echocardiography and MRI in diagnosing and managing myocardial diverticula.

17.
Cureus ; 16(2): e55106, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38558647

RESUMEN

Spontaneous coronary artery dissection (SCAD) is defined as a non-iatrogenic, non-traumatic separation of the coronary artery wall, which has gained considerable recognition as an important cause of acute coronary syndrome. Despite the emerging evidence, it is still frequently missed and requires a high index of suspicion, as failure to accurately identify SCAD promptly could prove fatal. SCAD is most prevalent among middle-aged women, although it can also be found in men and postmenopausal women. Risk factors of SCAD include exogenous hormone use, physical and emotional stressors, pregnancy, and several inflammatory and connective tissue disorders. COVID-19 also contributes to the prevalence of SCAD. SCAD is classified into four main types based on the angiographic findings - type 1, type 2, type 3, and type 4. The gold standard for diagnosis is coronary angiography; however, intracardiac imaging is useful if diagnostic doubts persist. Despite the increasing recognition of this disease, there is a paucity in the guidelines on the management of SCAD. Management may be conservative, medical, or interventional. Cardiac rehabilitation is also necessary in the management of patients with SCAD. In light of the gaps in evidence, the authors aim to provide a comprehensive review of the existing literature, outlining the pathophysiology, classification, and, most importantly, the evidence and pitfalls circulating diagnosis, acute, and long-term management of SCAD.

18.
Sci Rep ; 14(1): 5387, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443423

RESUMEN

In this study, we developed a novel nanocomposite, polyurethane foam impregnated with zero-valent iron nanoparticles (PU@nZVI), for the effective removal of chromium(VI) from various water sources. The characterization of nanocomposite (PU@nZVI) was performed by XRD, SEM-EDS, TEM and FT-IR techniques. Using the response surface methodology, we optimized the removal conditions, achieving an optimal pH of 2 and a dose of 0.5 g/L. The PU@nZVI demonstrated an excellent maximum adsorption capacity of 600.0 mg/g for Cr6+. The adsorption kinetics and isotherms were best described by the pseudo-second-order model and the Freundlich isotherm, respectively. Significantly, the nanocomposite removed 99.98% of Cr6+ from tap water, 96.81% from industrial effluent, and 94.57% from treated sewage wastewater. Furthermore, the PU@nZVI maintained its efficiency over five adsorption-desorption cycles, highlighting its reusability. These results suggest that the PU@nZVI nanocomposite is a highly efficient and sustainable option for chromium(VI) removal in water treatment applications.

19.
Sci Rep ; 14(1): 7342, 2024 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-38538682

RESUMEN

The present work aimed to investigate the effect of salinity in natural habitats in Egypt on the main secondary metabolites of Rosmarinus officinalis L. and Artemisia monosperma L. plants compared to plants grown at normal conditions. Plants grown under salinity were collected from Egyptian Western Coastal region habitats irrigated with underground water. Results showed that salinity increased the essential oil percentage of R. officinalis L. by 52.7% and A. monosperma L by 0.29% in addition to the total phenolics and flavonoids content in dry leaves compared to control plants. GC/MS analysis of rosemary essential oils revealed that salinity decreased the amount of some major oil monoterpenes component as verbenone, with a slight effect on 1,8 cineole and increased Camphor, endo- Boreneol, and linalool in addition to the appearance of new specific components such as Chrysanthenone monoterpene ketone and Caryophyllene sesquiterpene, while, in the case of Artemisia, the GC/MS showed that Artemisia ketone, Camphor, ß -phellandrene monoterpenes andα-Bisabolol sesquiterpenewere the major oil components; salinity decreased Camphor and ß -phellandrene content and increased artemisia ketone and α-Bisabolol oil content. About 11 new oil constituents were detected such as ( +)-2-Bornanone and Sesquisabinene hydrate. Mineral ions (N, K+, Ca+2, P, and Mg+2) uptake by R. officinalis and A. monosperma decreased in plants grown under salinity, while Na content increased compared to corresponding controls. Results demonstrated that both plants could tolerate the high salinity level in natural Western Coastal region soil which promoted more production of valuable secondary metabolites. The antimicrobial effect of R. officinalis L. and A. monosperma L. leaf methanolic extracts, results showed that R. officinalis extracts had an inhibitory response against all tested gram-positive and negative bacteria, in addition to the yeast (Candida albicans), whereas there was no any inhibitory effect concerning A. monosperma L extract on the tested species.


Asunto(s)
Antiinfecciosos , Artemisia , Monoterpenos Ciclohexánicos , Sesquiterpenos Monocíclicos , Aceites Volátiles , Rosmarinus , Alcanfor/farmacología , Egipto , Aceites Volátiles/farmacología , Monoterpenos/farmacología , Hojas de la Planta
20.
Sultan Qaboos Univ Med J ; 24(1): 127-130, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38434459

RESUMEN

Ramsay Hunt syndrome (RHS) is a triad of peri-auricular pain, ipsilateral facial nerve palsy and vesicular rash around the ear pinna. It is caused by reactivation of varicella-zoster virus (VZV) that lies dormant in the geniculate ganglia. It can be complicated by VZV encephalitis rarely. We report the case of an 8-year-old previously healthy boy who presented to a tertiary care hospital in Muscat, Oman in 2021 with fever, progressive left ear pain, vesicular rash around his ear pinna and left-sided facial nerve palsy. His course was complicated by VZV encephalitis where he was managed with intravenous (IV) acyclovir and IV corticosteroids. He improved significantly and was asymptomatic with a normal neurology examination at the 6-months follow-up.


Asunto(s)
Encefalitis , Exantema , Herpes Zóster Ótico , Masculino , Niño , Humanos , Herpes Zóster Ótico/complicaciones , Herpes Zóster Ótico/diagnóstico , Herpes Zóster Ótico/tratamiento farmacológico , Herpesvirus Humano 3 , Dolor , Parálisis
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