Risk Factors from Pregnancy to Adulthood in Multiple Sclerosis Outcome.

Multiple sclerosis (MS) is an autoimmune disease characterized by a robust inflammatory response against myelin sheath antigens, which causes astrocyte and microglial activation and demyelination of the central nervous system (CNS). Multiple genetic predispositions and environmental factors are known to influence the immune response in autoimmune diseases, such as MS, and in the experimental autoimmune encephalomyelitis (EAE) model. Although the predisposition to suffer from MS seems to be a multifactorial process, a highly sensitive period is pregnancy due to factors that alter the development and differentiation of the CNS and the immune system, which increases the offspring's susceptibility to develop MS. In this regard, there is evidence that thyroid hormone deficiency during gestation, such as hypothyroidism or hypothyroxinemia, may increase susceptibility to autoimmune diseases such as MS. In this review, we discuss the relevance of the gestational period for the development of MS in adulthood.

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring.

Introduction: Gestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring). Methods: Gestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10-E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment. Results: The HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring. Discussion: Gestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.

Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases.

Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T4), L-3,5,3'-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.

Using a ligate intestinal loop mouse model to investigate Clostridioides difficile adherence to the intestinal mucosa in aged mice.

Interaction of Clostridioides difficile spores with the intestinal mucosa contributes to the persistence and recurrence of the infection. Advanced age is one of the main risk factors for C. difficile infection and recurrence of the disease. However, interaction of C. difficile spores with the intestinal mucosa during aging has not been evaluated. In the present work, using intestinal ligated loop technique in a mouse model, we analyzed C. difficile spore adherence and internalization to the ileum and colonic mucosa during aging. Additionally, we provide visual documentation of the critical steps of the procedure. Consequently, our data suggest that spore internalization in the ileum and colonic mucosa is higher in elderly mice rather than adults or young mice. Also, our data suggest that spore adherence to the ileum and colonic mucosa decreases with aging.

Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection.

Clostridioides difficile spores produced during infection are important for the recurrence of the disease. Here, we show that C. difficile spores gain entry into the intestinal mucosa via pathways dependent on host fibronectin-α5ß1 and vitronectin-αvß1. The exosporium protein BclA3, on the spore surface, is required for both entry pathways. Deletion of the bclA3 gene in C. difficile, or pharmacological inhibition of endocytosis using nystatin, leads to reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model. Our findings indicate that C. difficile spore entry into the intestinal barrier can contribute to spore persistence and infection recurrence, and suggest potential avenues for new therapies.

Genotipos de VPH y cambios citológicos cervico-uterino en pacientes de una consulta ginecológica privada del Estado Carabobo, Venezuela. Marzo-octubre de 2017 / HPV genotypes and cervical cytological changes in patients who attended a private gynecology appointment in the state of Carabobo, March-October 2017

Resumen Introducción: La infección genital por el Virus de Papiloma Humano (VPH) se ha asociado con el cáncer cérvicouterino (CCE) al provocar la aparición de lesiones precursoras de cáncer en la zona de transformación de la unión escamo-columnar del cuello uterino. Existen más de 100 tipos de VPH, clasificados en bajo riesgo oncogénico (VPH-BR) y alto riesgo oncogénico (VPH-AR). Estudios reportan la infección por genotipos de alto riesgo en el 100% de los CCE. En Venezuela, el 67,7% de los CCE, se relacionan con el genotipo de VPH-AR 16. Objetivo: Detectar la presencia de VPH en pacientes con cambios citológicos cervicouterino. Metodología: Se incluyeron 49 pacientes que presentaban cambios citológicos, se tomaron las muestras de la región endocervical y exocervical para la detección y genotipificación del virus mediante la técnica de Multiple PCR. Resultados: Las alteraciones citológicas presentes fueron Células Escamosas Atípicas (69,4%), Células Glandulares Atípicas (4,1%), Lesión Escamosa Intraepitelial de Bajo Grado (16,3%), y Lesión Escamosa Intraepitelial de Alto Grado (10,2%). La detección molecular demostró que 16,3% presentaba VPH, 62,5% correspondían a VPH-AR, 25% a VPH-BR, 12,5% al genotipo 16 y no se detectó el genotipo 18. Se reportó un solo caso de coinfección. Conclusiones: A diferencia de otros estudios, no se encontró una relación estadísticamente significativa entre la presencia del virus y la aparición de cambios citológicos cervicouterino en esta población. No obstante, se detectaron genotipos de alto riesgo oncogénico, lo que puede traducirse en una mayor incidencia de cáncer cervicouterino a futuro.

Abstract Introduction: Genital infection by the Human Papilloma Virus (HPV) has been associated with cervical cancer (CC) since it causes the appearance of precursor cancer lesions in the transformation area of ​​the squamous-columnar junction of the cervix. There are more than 100 types of HPV that are classified as low oncogenic risk (LR-HPV) and high oncogenic risk (HR-HPV). Studies report that the infection by high-risk genotypes is present in 100% of CC. In Venezuela, 67.7% of CC is related to the HPV-16 genotype. Objective: This study seeks to detect the presence of HPV in patients with cervical cytological cell changes. Methodology : Forty-nine patients with cytological changes were studied. The endocervical and ectocervical areas were sampled to detect and genotype the virus by using the Multiplex PCR technique. Results: The cytological alterations presented were: Atypical Squamous Cells (69.4%), Atypical Glandular Cells (4.1%), Low-grade Squamous Intraepithelial Lesion (16.3%) and High-grade Squamous Intraepithelial Lesion (10.2%). Besides, the general molecular detection showed that 16.3% had HPV, 62.5% of it corresponded to HR-HPV, 25% to LR-HPV, and 12.5% ​​to genotype 16. The genotype 18 was not detected, and only one co-infection case was reported. Conclusions: Unlike other studies, a statistically significant relationship was not found between the virus presence and the appearance of cervical cytological cell changes in this population. However, genotypes with high oncogenic risk were detected, which may lead to a higher incidence of cervical cancer in the future.