Pathogenic CACNA1A mutations can result in paroxysmal attacks of encephalopathy, hemiplegia and cerebral edema. We report two patients with CACNA1A-associated encephalopathy, hemiplegia and contralateral hemispheric cerebral edema treated successfully with intravenous magnesium sulfate and dexamethasone. One patient met the clinical criteria for familial hemiplegic migraine. There is a paucity of guidance in the literature on how to manage these patients. Despite some discrepancies in the treatment protocols in our two cases, they indicate that magnesium and dexamethasone could be part of the treatment algorithm for these patients. Further research to delineate appropriate dosing and duration of therapy is needed.

This study aimed to evaluate the effects of dexamethasone on development, viability, antrum formation and ultrastructural integrity of bovine secondary follicles cultured in vitro for 18 days. Bovine ovaries were obtained from slaughterhouses and secondary follicles of ~150–200 µm diameter were isolated and cultured in the laboratory in TCM-199+ alone or supplemented with different concentrations of dexamethasone (1, 10, 100 and 1000 ng/ml). Follicle viability was evaluated after the culture period, using calcein-AM (viable) and ethidium homodimer (nonviable). Follicle diameters and antrum formation were evaluated at days 0, 6, 12 and 18. Before or after in vitro culture, follicles were fixed for histological and ultrastructural analysis. Follicle diameters were evaluated using analysis of variance and Kruskal–Wallis test, while chi-squared test was used to evaluate the percentage of viable follicles and antrum formation (P < 0.05). Follicles cultured for 6 days with all treatments increased their diameters significantly, but there was no significant difference between treatments at the end of the culture period. In vitro cultured follicles showed antral cavity formation at the end of the culture period, but no influence of dexamethasone was seen. Ultrastructural analysis showed that follicles cultured with dexamethasone (1, 10, 100 and 1000 ng/ml) had well preserved granulosa cells. However, oocytes from follicles cultured with 10, 100 or 1000 ng/ml dexamethasone showed signs of degeneration. It can be concluded that follicles cultured in vitro in the presence of dexamethasone demonstrated continuous in vitro growth, but oocytes from follicles cultured with 10, 100 or 1000 ng/ml dexamethasone had poor ultrastructure.

Glucocorticoids (GCs) are counterregulatory hormones with broad effects on the digestion and absorption of dietary carbohydrates, lipids and proteins, but the underlying molecular mechanisms of these effects remain unclear. The present experiment was conducted to investigate the main expression sites of nutrient transporters and the effects of GCs on the gene expression of these transporters in the rabbit small intestine. The results showed that peptide transporter 1 (PepT1), facultative amino acid transporter (rBAT), neutral amino acid transporter (B0AT), excitatory amino acid transporter 3 (EAAT3), sodium-glucose transporter 1 (SGLT1) and glucose transporter 5 (GLUT5) were mainly expressed in the distal segment, glucose transporter 2 (GLUT2) and fatty-acid-binding protein 4 (FATP4) were mainly expressed in the proximal segment and cationic amino acid transporter 1 (CAT1) was mainly expressed in the middle segment of the rabbit small intestine. In addition, we analysed the effects of 3 h (short-term) or 7 days (long-term) dexamethasone (DEX) treatment on the gene expression of most nutrient transporters. The results showed that short-term DEX treatment significantly decreased PepT1, B0AT, EAAT3, rBAT and SGLT1 expressions in all small intestinal segments, while it significantly decreased GLUT2 in the duodenum and FATP4 in the duodenum and ileum (P < 0.05). Long-term DEX treatment also significantly decreased PepT1, CAT1, B0AT, EAAT3, rBAT and SGLT1 in all small intestinal segments and significantly decreased GLUT2 in the jejunum and FATP4 in the ileum (P < 0.05). In conclusion, DEX could decrease the gene expression of most nutrient transporters (except GLUT5) and affect the transport of intestinal amino acids, monosaccharides and fatty acids.

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.

X-ray powder diffraction data, unit-cell parameters, and space group for 17- hydroxy-16-methyl-9,11-epoxypregna-1,4,6-triene-3,20-dione, C22H26O4, are reported [ a = 18.435(1) Å, b = 12.269(3) Å, c = 8.251(5) Å, α = 90°, β = 90°, γ = 90°, unit-cell volume V = 1866.43 Å3, Z = 4, ρcal = 1.261 g cm−3 and space group P212121]. All measured lines were indexed and are consistent with the P212121 space group. No detectable impurities were observed.

While beneficial for sow reproductive efficiency and biosecurity, segregated early weaning (SEW) leads to a systemic immune response that adversely affects the digestive physiology and post-weaning growth of pigs. Two experiments were conducted to evaluate the effects of a glucocorticoid receptor agonist (GA) on growth performance, measures of immune function and intestinal integrity of SEW pigs. In both experiments, pigs were fed corn-soybean meal-based starter diets. In the first experiment, 48 pigs (initial BW 4.8 ± 0.7 kg) were weaned at 21 ± 1 days and randomly assigned to three GA treatment groups: 0, 0.2 and 0.6 mg GA/kg of BW injected intramuscularly. Treatments were administered one day before weaning. Pigs in the 0 mg GA group received sterile saline in place of GA. Body weight was measured daily from one day before to 7 days post-weaning, and then weekly until 28 days post-weaning. Piglets treated with 0.2 mg GA had a higher BW than piglets in other treatment groups during the 28-day course of the study (P <0.02). To further explore the mechanisms behind this result, a second experiment was performed in which a total of 18 gilts (BW 5.6 ± 0.85 kg) were randomly assigned into three treatment groups: suckling plus saline (UWS), weaned treated with GA (WGA; 0.2 mg GA/kg BW) and weaned plus saline (CON). Treatments were administered one day before and 3 days post-weaning. The WGA and CON groups were weaned at 23 ± 2 days, while the UWS group remained with sow for the duration of the study. Body weight was measured daily and blood plasma was collected at 0, 1, 4 and 5 days post-weaning. All gilts were euthanized 5 days after weaning and jejunum samples were collected for mucosal scrapings, histomorphological analysis and gene expression analysis. Plasma levels of interleukin-1β (IL-1β) and haptoglobin were lower in WGA pigs compared with CON (P <0.02), while plasma total antioxidant capacity was higher in WGA pigs compared with both CON and UWS groups (P <0.01). Relative to CON, GA downregulated IL-18 gene expression in the jejunum, as assessed by both tissue homogenate and mucosal scrapings, but it upregulated claudin-IV gene expression only in the tissue homogenate (P <0.01). These results suggest that GA treatment improves the growth performance of SEW pigs in part by mitigating the negative effects of systemic inflammation. However, the effect of GA on barrier integrity requires further investigation.

Hayward GN, Hay AD, Moore MV, et al. Effect of oral dexamethasone without immediate antibiotics vs. placebo on acute sore throats in adults: a randomized clinical trial. JAMA 2017;317(15):1535-43.

Toxoplasmosis is a serious zoonoses disease and opportunistic, and can be life-threatening. Dexamethasone (DEX) is widely used in the clinic for treatment of inflammatory and autoimmune diseases. However, long-term use of DEX is often easy to lead to acute toxoplasmosis in patients, and the potential molecular mechanism is still not very clear. The aims of this study were to investigate the effect of DEX on proliferation of Toxoplasma and its molecular mechanisms, and to establish the corresponding control measures. All the results showed that dexamethasone could enhance the proliferation of Toxoplasma gondii tachyzoites. After 72 h of DEX treatment, 566 (±7) tachyzoites were found in 100 host cells, while only 86 (±8) tachyzoites were counted from the non-treated control cells (P < 0·01). Gas chromatography (GC) analysis showed changes in level and composition of fatty acids in DEX-treated host cells, and T. gondii. Fish oil was added as a modulator of lipid metabolism in experimental mice. It was found that mice fed with fish oil did not develop the disease after infection with T. gondii, and the structure of fatty acids in plasma changed significantly. The metabolism of fatty acid in the parasites was limited, and the desaturase gene expression was downregulated. These results indicate that the molecular mechanism of dexamethasone to promote the proliferation of T. gondii may be that dexamethasone induces the change of fatty acids composition of tachyzoites and host cells. Therefore, we recommend supplementation of fatty acid in immunosuppressive and immunocompromised patients in order to inhibit toxoplasmosis.

Maternal treatment with dexamethasone (Dex) in threatening preterm delivery alters activities at the hypothalamic–pituitary–adrenal axis in the offspring. This alteration may interfere with reproductive function. The impact of gestational Dex exposure on male reproductive function of the offspring was investigated. A total of 25 pregnant rats randomly assigned to five groups (n=5) were treated with normal saline (control), Dex (100 μg/kg/day sc) during gestation days (GD) 1–7, 8–14, 15–21 and 1–21, respectively. Birth weight, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile and histopathology of testis and epididymis were determined in the F1 and F2 offspring. Results showed a significant increase (P<0.05) in pubertal age, serum corticosterone and gonadotropin-releasing hormone (GnRH) levels in the male offspring of DexGD 15–21 and 1–21 groups and a significant decrease (P<0.05) in serum testosterone, luteinizing hormone, birth weight and AGD at birth in the male F1 offspring. In the F2 offspring, there was a significant reduction (P<0.05) in serum corticosterone, testosterone, follicle-stimulating hormone and GnRH when compared with the control. Dex treatment at GD 15–21 and 1–21 significantly reduced (P<0.05) sperm motility and normal morphology in the F1 and F2 offspring. Maternal Dex treatment in rats during late gestation may disrupt sexual development markers in the F1 and F2 male offspring.

Introduction: Croup is one of the most common childhood respiratory illnesses, affecting more than 80,000 Canadian children per year. Early dexamethasone administration in croup can reduce admission rates and length of stay (LOS), as well as return visits to the emergency department (ED). Pre-hospital emergency medical services (EMS) teams in Edmonton administer dexamethasone to children with croup. The objectives of this study were to (a) assess the clinical impact of pre-hospital administration of dexamethasone to children with croup and (b) compare clinical outcomes of these patients to those who did not receive their first dose of dexamethasone via the EMS providers. Methods: This study was a retrospective medical record review that included children between 6 months and 6 years of age who were brought via EMS to the Stollery Children’s Hospital ED with a final diagnosis of croup, between January 1st 2010 and December 31st 2012. Data were collected regarding pre-hospital presentation and management, ED presentation and management, ED LOS and final disposition, and patient demographics. Results: 188 patients were enrolled, 35.1% (66/188) of whom received a pre-hospital diagnosis of croup. The mean age of the participants was 32.96 months (SD±17.18). Overall, 10.6% patients (20/188) were given dexamethasone in the pre-hospital setting, while 30.3% patients (57/188) were given nebulized epinephrine by EMS. Out of the 66 patients with a pre-hospital diagnosis of croup, 10.6% (n=7) were given dexamethasone by EMS. In the ED, dexamethasone was administered to 88.3% of patients (166/188) while 56/188 participants (29.8%) received nebulized epinephrine. There was no statistically significant difference in ED LOS stay between those who received pre-hospital dexamethasone (2.6 hours, SD±1.6, n=18) and those who did not (3.3 hours, SD±2.7, n=159). The number of in-hospital epinephrine doses per patient was influenced by the administration of pre-hospital dexamethasone (p=0.010). Conclusion: Pre-hospital administration of dexamethasone likely influences the severity and short-term persistence of croup symptoms, as evidenced by less epinephrine use in the ED. Contrary to current EMS guidelines, very few patients with a pre-hospital diagnosis of croup received dexamethasone by EMS personnel. This likely represents a missed opportunity to decrease the severity of the patients’ disease.

Considering the negative effects of glucocorticoid treatment, especially during fetal development it is important to investigate effectors decreasing such disadvantages. The aim of this study was to investigate the effect of prenatally administered dexamethasone (Dex), a synthetic glucocorticoid, on the histomorphometry of the femur in the offspring of spiny mice. The study was performed on 24 pregnant spiny mice. The time of the experiment included the prenatal period between the 20th day of gestation until birth (pregnancy lasts on average of 36–38 days). The mice from the experimental group received dexamethasone per os in a dose of 125 mg/kg birth weight daily. At the end, the newborns from the experimental and control group were weighted and euthanized. Maternal Dex treatment resulted in a 17% decrease in birth weight in newborns. Dex administration significantly reduced the thickness of the hypertrophy zone of the growth plate by 34% and total thickness by 8,7%. In addition, Dex decreased the number of cells in the articular cartilage by 27% and significantly decreased their diameter by 5%. Dex also affected the structure and spatial distribution of thick and thin collagen fibers, lowering the proportion of thin fibers compared with the control group. Moreover, Dex treatment considerably lowered the amount of proteoglycans in articular and growth cartilages. Exposure to glucocorticoids in pregnant spiny mice affects cartilage development by accelerating maturity of collagen fibers and growth plate, presumably along with further disruption of longitudinal growth of long bones.

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.