Ovariectomy and subsequent replacement of 17β-estradiol by means of silastic capsules and peroral Nutella are demonstrated in rats ...

Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

The use of animal models, especially the rat, is crucial for elucidating the biological effects and mechanisms of the widely used hormone 17β‐oestradiol. Unfortunately, there is a lack of consensus on optimal means of obtaining and maintaining physiological 17β‐oestradiol concentrations in plasma and this may be the reason for the varying results in several studies, including the disagreement on whether 17β‐oestradiol is neuroprotective or not. Very few studies have been devoted to investigating the characteristics and biological relevance of different methods of 17β‐oestradiol administration. We therefore ovariectomized 75 Sprague‐Dawley rats and, following a 2‐week washout period, administered 17β‐oestradiol using three different methods; daily injections (10 µg 17β‐oestradiol/kg), slow‐release pellets (0.25 mg 60 day‐release pellets, 0.10 mg 90 day‐release pellets) and silastic capsules (with/without washout periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with 20 mm columns of 180 µg 17β‐oestradiol/mL sesame oil). A further 45 animals were used as ovariectomized and native controls studied in different parts of the oestrous cycle. Silastic capsules produced concentrations of 17β‐oestradiol within the physiological range 4–5 weeks independently of whether a prior washout period was included or not. The slow‐release pellets, irrespective of dose or release period, resulted in initial concentrations an order of magnitude above physiological concentrations during the first 2 weeks followed by a substantial decrease. Daily injections resulted in increasing 17β‐oestradiol concentrations, but within physiological levels. Silastic capsules are conveniently manufactured and used and are superior to pellets and injections in reliably producing long‐term 17β‐oestradiol concentrations within the physiological range.

Fever after stroke is common, and often caused by infections. In the current study, we aimed to test the hypothesis that pneumonia, urinary tract infection and all-cause fever (thought to include at least some proportion of endogenous fever) have different predicting factors, since they differ regarding etiology. PubMed was searched systematically for articles describing predictors for post-stroke pneumonia, urinary tract infection and all-cause fever. A total of 5294 articles were manually assessed; first by title, then by abstract and finally by full text. Data was extracted from each study, and for variables reported in 3 or more articles, a meta-analysis was performed using a random effects model. Fifty-nine articles met the inclusion criteria. It was found that post-stroke pneumonia is predicted by age OR 1.07 (1.04–1.11), male sex OR 1.42 (1.17–1.74), National Institutes of Health Stroke Scale (NIHSS) OR 1.07 (1.05–1.09), dysphagia OR 3.53 (2.69–4.64), nasogastric tube OR 5.29 (3.01–9.32), diabetes OR 1.15 (1.08–1.23), mechanical ventilation OR 4.65 (2.50–8.65), smoking OR 1.16 (1.08–1.26), Chronic Obstructive Pulmonary Disease (COPD) OR 4.48 (1.82–11.00) and atrial fibrillation OR 1.37 (1.22–1.55). An opposite relation to sex may exist for UTI, which seems to be more common in women. The lack of studies simultaneously studying a wide range of predictors for UTI or all-cause fever calls for future research in this area. The importance of new research would be to improve our understanding of fever complications to facilitate greater vigilance, monitoring, prevention, diagnosis and treatment.

Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens’ actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings.