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PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
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Vacina BCG , Doença Granulomatosa Crônica , NADPH Oxidase 2 , Tuberculose , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/complicações , Vacina BCG/efeitos adversos , Masculino , Feminino , Criança , Tuberculose/epidemiologia , Tuberculose/imunologia , Pré-Escolar , Lactente , Adolescente , NADPH Oxidase 2/genética , Estudos de Coortes , Mycobacterium bovis , México/epidemiologia , Antituberculosos/uso terapêutico , NADPH Oxidases/genéticaRESUMO
Soldiers of the Mexican Army with obesity were subjected to an intense 60-day weight-loss course consisting of a controlled diet, daily physical training, and psychological sessions. The nutritional treatment followed the European Society of Cardiology (ESC) recommendations, incorporating elements of the traditional milpa diet in the nutritional intervention. The total energy intake was reduced by 200 kcal every 20 days, starting with 1,800 kcal and ending with 1,400 kcal daily. On average, the participants reduced their body weight by 18 kg. We employed an innovative approach to monitor the progress of the twelve soldiers who completed the entire program. We compared the untargeted metabolomics profiles of their urine samples, taken before and after the course. The data obtained through liquid chromatography and high-resolution mass spectrometry (LC-MS) provided insightful results. Classification models perfectly separated the profiles pre and post-course, indicating a significant reprogramming of the participants' metabolism. The changes were observed in the C1-, vitamin, amino acid, and energy metabolism pathways, primarily affecting the liver, biliary system, and mitochondria. This study not only demonstrates the potential of rapid weight loss and metabolic pathway modification but also introduces a non-invasive method for monitoring the metabolic state of individuals through urine mass spectrometry data.
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Militares , Obesidade , Redução de Peso , Humanos , Masculino , Obesidade/metabolismo , Obesidade/dietoterapia , Obesidade/terapia , Redução de Peso/fisiologia , Adulto , Metabolômica , Adulto Jovem , Metabolismo Energético/fisiologia , Espectrometria de Massas , Dieta Redutora , Programas de Redução de Peso/métodos , Reprogramação MetabólicaRESUMO
Orthopterygium huaucui, commonly known as "Pate", is a medicinal shrub belonging to the Anacardiaceae family used locally to treat burns and stomach pains. Endemic to Peru, chemical studies on O. huaucui are limited. In this study, UHPLC/ESI/MS/MS was used to identify secondary metabolites in leaves, stems and fruits, and the antioxidant capacities of the different parts were compared. In addition, several compounds such as methyl gallate, gallic acid, kaempferol, quercetin, and quercetin 3-O-ß-glucuronide were successfully isolated from the methanolic extract of the leaves of this species for the first time. Untargeted UHPLC Q/Orbitrap/ESI/MS/MS analysis tentatively identified seventy-six compounds in the different parts of the plant, showing that this species as an interesting source of flavonoids, procyanidins and tannins. The phenolic content in leaves and stems was 334.31±4.34 and 295.18±6.38 gallic acid equivalents/100 g dry plant, respectively, while that of fruits was lower (99.92±5.45 mg/100 g). Leaves had twice the flvonoid content than fruits (210.38±3.85 versus 87.42±3.85 quercetin equivalents/100 g). DPPH) results indicated high antioxidant activity in all parts, with stems and leaves showing IC50 of 12.8 µg/mL, and fruits showing less activity (IC50 = 38.6 µg/mL). ORAC test showed higher antioxidant values in the stems (467.82±21.17 µmol Trolox equivalents/100 g).
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The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, and treatment is crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that the inflammatory component involves cytokines and free radicals, these conditions must be treated to reduce the current symptoms and provide neuroprotection to reduce the risk of a long-term neurodegenerative disease. It has been shown that cannabis has compounds with immunomodulatory and antioxidant functions in other pathologies. Therefore, exploring this approach could provide a viable therapeutic option for PCC, which is the purpose of this review. This review involved an exhaustive search in specialized databases including PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, and Clinical Trials. Phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and Delta-9-tetrahydrocannabinol (THC), exhibit significant antioxidative and anti-inflammatory properties and have been shown to be an effective treatment for neuroinflammatory conditions. These compounds could be promising adjuvants for PCC alone or in combination with other antioxidants or therapies. PCC presents significant challenges to neurological health, and neuroinflammation and oxidative stress play central roles in its pathogenesis. Antioxidant therapy and cannabinoid-based approaches represent promising areas of research and treatment for mitigating adverse effects, but further studies are needed.
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COVID-19 , Cannabis , Alucinógenos , Doenças Neurodegenerativas , Humanos , Síndrome de COVID-19 Pós-Aguda , Antioxidantes/uso terapêutico , Doenças Neuroinflamatórias , COVID-19/complicações , Agonistas de Receptores de CanabinoidesRESUMO
Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.
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Epilepsia do Lobo Temporal , Epilepsia , Piracetam , Humanos , Ratos , Animais , Levetiracetam/farmacologia , Levetiracetam/uso terapêutico , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/genética , Transcriptoma , Piracetam/farmacologia , Piracetam/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Giro DenteadoRESUMO
Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms.
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Aptâmeros de Nucleotídeos , Doenças Transmissíveis , Humanos , Técnica de Seleção de Aptâmeros , Bactérias Gram-Negativas/genética , BactériasRESUMO
Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.
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Aberrações dos Cromossomos Sexuais , Trissomia , Humanos , Feminino , Trissomia/diagnóstico , Trissomia/genética , Deleção Cromossômica , Fenótipo , CariótipoRESUMO
The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport. Although brain endothelial cell function is crucial for brain homeostasis, their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia, astroglia, neurons, or even molecules such as amyloid beta, Tau, or alpha-synuclein. Alzheimer's disease is the most common neurodegenerative disease, and brain endothelial cell dysfunction has been reported by several groups. However, its impairment has barely been considered as a potential therapeutic target. Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease, highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment. Finally, we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.
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Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.