Effects of minocycline on endogenous neural stem cells after experimental stroke.

Minocycline has been reported to reduce infarct size after focal cerebral ischemia, due to an attenuation of microglia activation and prevention of secondary damage from stroke-induced neuroinflammation. We here investigated the effects of minocycline on endogenous neural stem cells (NSCs) in vitro and in a rat stroke model. Primary cultures of fetal rat NSCs were exposed to minocycline to characterize its effects on cell survival and proliferation. To assess these effects in vivo, permanent cerebral ischemia was induced in adult rats, treated systemically with minocycline or placebo. Imaging 7 days after ischemia comprised (i) Magnetic Resonance Imaging (MRI), assessing the extent of infarcts, (ii) Positron Emission Tomography (PET) with [(11)C]PK11195, characterizing neuroinflammation, and (iii) PET with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT), detecting proliferating endogenous NSCs. Immunohistochemistry was used to verify ischemic damage and characterize cellular inflammatory and repair processes in more detail. In vitro, specific concentrations of minocycline significantly increased NSC numbers without increasing their proliferation, indicating a positive effect of minocycline on NSC survival. In vivo, endogenous NSC activation in the subventricular zone (SVZ) measured by [(18)F]FLT PET correlated well with infarct volumes. Similar to in vitro findings, minocycline led to a specific increase in endogenous NSC activity in both the SVZ as well as the hippocampus. [(11)C]PK11195 PET detected neuroinflammation in the infarct core as well as in peri-infarct regions, with both its extent and location independent of the infarct size. The data did not reveal an effect of minocycline on stroke-induced neuroinflammation. We show that multimodal PET imaging can be used to characterize and quantify complex cellular processes occurring after stroke, as well as their modulation by therapeutic agents. We found minocycline, previously implied in attenuating microglial activation, to have positive effects on endogenous NSC survival. These findings hold promise for the development of novel treatments in stroke therapy.

Grayling (Thymallinae) phylogeny within salmonids: complete mitochondrial DNA sequences of Thymallus arcticus and Thymallus thymallus.

The phylogenetic relationships among the three subfamilies (Salmoninae, Coregoninae and Thymallinae) in the Salmonidae have not been addressed extensively at the molecular level. In this study, the whole mitochondrial genomes of two Thymallinae species, Thymallus arcticus and Thymallus thymallus were sequenced, and the published mitochondrial genome sequences of other salmonids were used for Bayesian and maximum-likelihood phylogenetic analyses. These results support an ancestral Coregoninae, branching within the Salmonidae, with Thymallinae as the sister group to Salmoninae.

FLIP&FLAP-a training programme for children and adolescents with epilepsy, and their parents.

OBJECTIVE: The objective of this article is to present the development, contents and efficacy of the FLIP&FLAP programme for children and adolescents with epilepsy, and their parents. INTERVENTION: The programme is mainly directed at age-appropriately developed children and adolescents between 6 and 16 who take antiepileptic drugs. It is conducted as a 2.5-day group training programme; children and parents are grouped separately. The main focuses are: EVALUATION STUDY: We performed a multi-centre non-randomised two-group pre-/post-trial using a waiting-list control group design. 10 German epilepsy centres participated. The intervention group, IG (21 children 8-11 years, 44 adolescents 12-16 years, 72 parents) completed standardised questionnaires immediately before the FLIP&FLAP course and 6 months later; the waiting control group, WCG (31 children, 39 adolescents, 72 parents) 6 months before and immediately before the course. Compared to the WCG, the children and parents of the IG showed significantly improved knowledge of epilepsy, with medium to large effect sizes (univariate analysis of variance with repeated measurements, d=0.6-1.4). Parents of the IG reported improved self-management skills (d=0.7) and communication skills (d=0.8) of their child and fewer epilepsy-related worries (d=0.5). Children and adolescents of the IG reported improved HRQOL in the Social Exclusion dimension (d=0.3). CONCLUSION: FLIP&FLAP is an effective child- and family-centred programme. It is currently being established in Northern Germany to test its usefulness in routine care.

Evidence for an acute rise of intestinal calcium absorption in response to aerobic exercise.

BACKGROUND: The acute effects of physical activity on intestinal calcium (Ca) uptake and on bone metabolism are not known. AIM OF THE STUDY: To investigate the consequences of an acute aerobic exercise bout on fractional Ca absorption and on biomarkers of bone turnover. METHODS: With the use of a cross over design, eighteen male athletes, aged 25.2 (SE 0.6) years, either had to perform a 60 min run (70 % of maximal speed) or had to rest for 60 min. Intestinal Ca absorption (Fc(240)) was assessed by the use of a stable strontium test. Moreover, calciotropic hormones and serum C-Telopeptide (CTx), a biomarker of bone collagen degradation, and serum C-terminal propeptide of type I collagen (PICP), a marker of bone collagen formation, were measured prior (t(-60)) and 3 hours after (t(240)) exercise or rest. RESULTS: Fc(240) values were significantly enhanced in response to exercise compared to rest (16.2 +/- 0.7 % vs. 14.6 +/- 0.8 %; P < 0.05). PICP values were significantly lower in response to exercise compared to rest: -9.8 % (P < 0.05). Exercise did not influence serum levels of intact parathyroid hormone and calcitriol. Serum CTx levels decreased markedly between t(-60) and t(240) during both intervention periods (both P values < 0.001), the results being in line with the circadian rhythm of serum CTx. CONCLUSIONS: A moderate exercise bout can induce an acute rise in fractional Ca absorption. Moreover, even in endurance-trained young men a moderate exercise bout acutely decreases bone collagen formation, while the physiologic fluctuations of the bone resorption marker CTx remain unaffected.

Exercise-trained young men have higher calcium absorption rates and plasma calcitriol levels compared with age-matched sedentary controls.

The effect of physical activity on human calcium (Ca) metabolism is still not completely understood. Thus, we investigated fractional Ca absorption using a stable strontium test (Fc(240)), calciotropic hormones, and renal Ca excretion in 31 young men with a high activity level (GH) and in 26 age-matched sedentary control subjects (GL). Weekly hours spent on physical activity, obtained with a questionnaire were 15.0 +/- 6.6 (GH) and 1.0 +/- 1.4 (GL), respectively. Serum testosterone levels were significantly lower in GH compared with GL (P < 0.005). Dietary Ca intake (4-day food record) was twice as high in GH compared with GL men (P < 0.001). GH had significantly higher serum calcitriol levels and Fc(240) values than GL (P < 0.001 and P < 0.01, respectively). In a stepwise multiple regression analysis including serum levels of 25-hydroxyvitamin D, calcitriol, testosterone, and dietary Ca intake, only calcitriol was significantly correlated with Fc(240) (P = 0. 017). Twenty-four hour renal Ca excretion was only slightly higher in GH compared with GL (P < 0.05). However, additional Ca losses might have occurred through the extensive sweating of GH, as indicated by a difference of 1.7 liter between fluid intake and renal fluid excretion (P < 0.001). In summary, we observed a higher fractional Ca absorption rate in physically active young men compared with sedentary controls which is probably mediated by calcitriol. The low testosterone serum levels of the athletes were obviously not a limiting factor in Ca absorption efficiency. An additional Ca retention might, however, only be obtained if absorbed Ca exceeded total obligatory Ca losses.