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Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic–pituitary–adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of Ghrh and Sst in the hypothalamus does not change, except for Npy and Agrp, while at the pituitary level the Gh, Ghrhr and Ghr genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated Ghr and Igf1r expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.

Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic–pituitary–gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE.

Drug hypersensitivity reactions (DHRs) are a type of adverse drug reactions with heterogeneous pathophysiological mechanisms and a broad spectrum of clinical manifestations. Since over-diagnosing is common in children, a complete allergy work-up is needed. A cross-sectional study was conducted at a tertiary care institution, covering the five-year period. Five hundred and four patients of both sexes, mean age 7.5 and with a medical history suggestive of DHR were evaluated. ENDA/EAACI guidelines were used for a diagnostic algorithm. Single drug hypersensitivity was registered in 375 patients and multiple drug hypersensitivity in 129. The main culprits in medical history were antibiotics (83%), non-steroidal anti-inflammatory drugs (NSAIDs) (8.4%) and analgoantipyretics (3.8%). Skin involvement was registered in 96.2%. DHRs were confirmed in 4.4% patients—six patients had positive skin tests and 13 had a positive drug provocation test. In the proven DHRs group, the main agents were antibiotics (72.7%), followed by NSAIDs (8.3%), and of all the skin manifestations, urticaria was most common (78.2%), followed by exanthema (10.5%) and angioedema (5.3%). Considering the above, anticipating DHRs and a proper referral of children to an allergologist is a key step in the assessment of drug hypersensitivity. A complete allergy work-up prevents unnecessary drug exclusion and allows most children to safely continue the use of first-line medications when needed.

Therapeutic recommendations for pediatric acute respiratory distress syndrome (PARDS) include conventional (CMV) and rescue high-frequency oscillatory mode (HFOV) of mechanical ventilation (MV). The pediatric risk of mortality (PRISM) is a frequently used mortality score for critically ill patients. In search of methods to recognize those patients, we analyzed the PRISM III score as a potential predictor of the short-term outcome in MV subjects with PARDS. A retrospective five-year study of PARDS in children on MV was conducted in the Pediatric ICU. Seventy patients were divided into two groups (age group

Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2− levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.

Preschool children are particularly susceptible to recurrent upper and lower respiratory tract infections due to their immune immaturity and other contributing factors. Preventing and/or treating children suffering from recurrent respiratory tract infections (RRTIs) is challenging, and it is important to provide more clinical evidence about the safety and efficacy of natural immunomodulating preparations, including β-glucans. The aim of the present study was to assess the incidence of respiratory tract infections (RTIs) in children with a history of RRTIs for a period of 6 months (3 months of pleuran supplementation and 3 months of follow-up) compared with the same period from October to March of the previous year prior to enrolment in the study. A total of 1,030 children with a mean age of 3.49 ± 1.91 years from seven countries were included in this study. The total number of RTIs observed during the study period was significantly lower compared to the same period of the previous year (7.07 ± 2.89 vs. 3.87 ± 3.19; p