RESUMEN
Alzheimer's disease (AD) is a prevalent form of neurodegenerative disease with a complex pathophysiology that remains not fully understood, and the exact mechanism of neurodegeneration is uncertain. Ferroptosis has been linked to the progression of degenerative diseases observed in AD models. The present study is designed to investigate the protective effects of spermidine, a potent antioxidant and iron chelator, and its synergistic interactions with ciprofloxacin, another iron chelator, in modulating ferroptosis and mitigating AD progression in rats. This study investigated AD-related biomarkers like neurotoxic amyloid beta (Aß), arginase I, and serotonin. Spermidine demonstrated an anti-ferroptotic effect in the AD model, evident from the modulation of ferroptosis parameters such as hippocampus iron levels, reduced protein expression of transferrin receptor 1 (TFR1), and arachidonate 15-lipoxygenase (ALOX15). Additionally, the administration of spermidine led to a significant increase in protein expression of phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) and upregulation of Cystine/glutamate transporter (SLC7A11) gene expression. Moreover, spermidine notably decreased p53 protein levels, acrolein, and gene expression of spermidine/spermine N1-acetyltransferase 1 (SAT1). Overall, our findings suggest that spermidine and/or ciprofloxacin may offer potential benefits against AD by modulating ferroptosis. Furthermore, spermidine enhanced the antioxidant efficacy of ciprofloxacin and reduced its toxic effects.
Asunto(s)
Enfermedad de Alzheimer , Ferroptosis , Enfermedades Neurodegenerativas , Ratas , Masculino , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Espermidina/farmacología , Espermidina/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Péptidos beta-Amiloides/metabolismo , Estrés Oxidativo , Ciprofloxacina/farmacología , Quelantes del Hierro/farmacología , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
The foremost neurodegenerative disease is Alzheimer's (AD), which is characterized as a gradual decrease in memory, cognitive function, and also personal changes occurred. This study aims to assess the role of boswellic bioactive component in control Alzheimer's disease through enhancing mitochondrial electron transport chain complexes in the rat model. Rats were divided into five equal groups: the control group (G1), boswellic acid control group (G2), AD disease group (G3), boswellic acid -pre-treated group (G4) and boswellic acid-treated group (G5). At the end of the experiment, blood glucose level, tau protein, different neurochemicals parameters (dopamine, acetylcholine), L-malondialdehyde (MDA) levels, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities was determined. Also, GLUT2 and mitochondrial electron transport chain complexes were evaluated. As a result, an increase in hippocampus glucose, tau protein expression, MDA and GLUT2 in the AD group (G3) compared to control groups (G1 and G2) has been recorded. These parameters were declined after pre (G4) and treated (G5) by boswellic acid. The neurochemicals, antioxidants parameters, four mitochondrial chain complexes activities and their gene expression in the hippocampus of the AD group were decreased compared to the control groups (G1 and G2). In contrast, pre and treated groups by boswellic acid (G4 and G5, respectively) have shown an increase in antioxidants parameters, and the activities of four mitochondrial complexes, with the best improvement in the pre-treated group (G4), then treated group (G5). In conclusion; the boswellic acid improved the antioxidant and mitochondrial complexes in Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Expresión Génica/efectos de los fármacos , Hipocampo/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Triterpenos/farmacología , Animales , Glutatión Peroxidasa/metabolismo , Hipocampo/metabolismo , Malondialdehído/metabolismo , Ratas , Superóxido Dismutasa/metabolismo , Proteínas tau/metabolismoRESUMEN
BACKGROUND: Minimal hepatic encephalopathy (MHE) is not associated with overt neuropsychiatric symptoms but rather with subtle changes in psychometric and/or neurophysiologic tests. We aimed to diagnose MHE in children with extrahepatic portal vein obstruction (EHPVO) and to evaluate the effect of lactulose on MHE. METHODS: A prospective study was carried out on 30 patients with EHPVO (21 males; mean age 10±2.5 years). The study was carried out in the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Cairo, Egypt, between 2011 and 2013. All patients were subjected to clinical and laboratory assessment, neuropsychmetric testing using the arabic version of Wechsler intelligence tests, neurophysiological testing by visual electroencephalogram and P300 event related potentials (ERP). RESULTS: The prevalence of MHE among children with EHPVO was 20% (6/30). After randomization to treatment and no-treatment groups using lactulose, all tests were repeated after three months. Among four patients with MHE who received lactulose, three (75%) improved. On the other hand, one of the patients in the no-treatment group developed MHE. Only one patient in the treatment arm had to discontinue lactulose because of severe diarrhea. CONCLUSIONS: This pilot study revealed that the prevalence of MHE was 20%. Improvement on psychometic tests was seen in 75% of our patients (3/4) after treatment with lactulose. Lactulose treatment was well tolerated.
Asunto(s)
Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/psicología , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Hipertensión Portal/tratamiento farmacológico , Lactulosa/uso terapéutico , Distribución de Chi-Cuadrado , Niño , Estudios de Cohortes , Egipto , Electroencefalografía/métodos , Femenino , Estudios de Seguimiento , Enfermedad Veno-Oclusiva Hepática/complicaciones , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Hospitales Universitarios , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Pruebas de Función Hepática , Masculino , Pruebas Neuropsicológicas , Proyectos Piloto , Estudios Prospectivos , Psicometría , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Health clinics in rural Africa are typically resource-limited. As a result, many patients presenting with fever are treated with anti-malarial drugs based only on clinical presentation. This is a considerable issue in Uganda, where malaria is routinely over-diagnosed and over-treated, constituting a wastage of resources and an elevated risk of mortality in wrongly diagnosed patients. However, rapid diagnostic tests (RDTs) for malaria are increasingly being used in health facilities. Being fast, easy and inexpensive, RDTs offer the opportunity for feasible diagnostic capacity in resource-limited areas. This study evaluated the rate of malaria misdiagnosis and the accuracy of RDTs in rural Uganda, where presumptive diagnosis still predominates. Specifically, the diagnostic accuracy of "gold standard" methods, microscopy and PCR, were compared to the most feasible method, RDTs. METHODS: Patients presenting with fever at one of two health clinics in the Kabarole District of Uganda were enrolled in this study. Blood was collected by finger prick and used to administer RDTs, make blood smears for microscopy, and blot Whatman FTA cards for DNA extraction, polymerase chain reaction (PCR) amplification, and sequencing. The accuracy of RDTs and microscopy were assessed relative to PCR, considered the new standard of malaria diagnosis. RESULTS: A total of 78 patients were enrolled, and 31 were diagnosed with Plasmodium infection by at least one method. Comparing diagnostic pairs determined that RDTs and microscopy performed similarly, being 92.6 and 92.0 % sensitive and 95.5 and 94.4 % specific, respectively. Combining both methods resulted in a sensitivity of 96.0 % and specificity of 100 %. However, both RDTs and microscopy missed one case of non-falciparum malaria (Plasmodium malariae) that was identified and characterized by PCR and sequencing. In total, based on PCR, 62.0 % of patients would have been misdiagnosed with malaria if symptomatic diagnosis was used. CONCLUSIONS: Results suggest that diagnosis of malaria based on symptoms alone appears to be highly inaccurate in this setting. Furthermore, RDTs were very effective at diagnosing malaria, performing as well or better than microscopy. However, only PCR and DNA sequencing detected non-P. falciparum species, which highlights an important limitation of this test and a treatment concern for non-falciparum malaria patients. Nevertheless, RDTs appear the only feasible method in rural or resource-limited areas, and therefore offer the best way forward in malaria management in endemic countries.