Neuroprotective DAMPs member prothymosin alpha has additional beneficial actions against cerebral ischemia-induced vascular damages

AbstractProthymosin alpha (ProTα) suppresses stress-induced necrosis of cultured cortical neurons. As neuroprotection alone could not explain the long-lasting protective actions against cerebral ischemia by ProTα, we further examined whether ProTα, in addition to neuroprotective effects, has other anti-ischemic activities. When recombinant mouse ProTα (rmProTα) at 0.3 mg/kg was intravenously (i.v.) given 2 h after the start of tMCAO, all mice survived for more than 14 days. In evaluation of CD31- and tomato lectin-labeling as well as IgG and Evans blue leakage, rmProTα treatment (0.1 mg/kg) largely blocked ischemia-induced vascular damages. Therefore, rmProTα has novel beneficial effects against ischemia-induced brain damage through vascular mechanisms

Endogenous oxytocin levels in extracted saliva elevates during breastfeeding correlated with lower postpartum anxiety in primiparous mothers

Background: Breastfeeding in the early postpartum period is expected to have mental benefits for mothers; however, the underlying sychobiological mechanisms remain unclear. Previously, we hypothesized that the release of oxytocin in response to the suckling stimuli during breastfeeding would mediate a calming effect on primiparous mothers, and we examined salivary oxytocin measurements in primiparous mothers at postpartum day 4 using saliva samples without extraction, which was erroneous. Thus, further confirmation of this hypothesis with a precise methodology was needed.Methods: We collected saliva samples at three time points (baseline, feeding, and post-feeding) to measure oxytocin in 24 primiparous mothers on postpartum day 2 (PD2) and 4 (PD4) across the breastfeeding cycle. Salivary oxytocin levels using both extracted and unextracted methods were measured and compared to determine the qualitative differences. State and trait anxiety and clinical demographics were evaluated to determine their association with oxytocin changes.Results: Breastfeeding elevated salivary oxytocin levels; however, it was not detected to a significant increase in the extraction method at PD4. We found a weak but significant positive correlation between changes in extracted and unextracted oxytocin levels during breastfeeding (feeding minus baseline); there were no other significant positive correlations. Therefore, we used the extracted measurement index for subsequent analysis. We showed that the greater the increase in oxytocin during breastfeeding, the lower the state anxiety, but not trait anxiety. Mothers who exclusively breastfed at the 1-month follow-up tended to be associated with slightly higher oxytocin change at PD2 than those who did not.Conclusions: Breastfeeding in early postpartum days could be accompanied by the frequent release of oxytocin and lower state anxiety, potentially contributing to exclusive breastfeeding

Slitrk2 deficiency causes hyperactivity with altered vestibular function and serotonergic dysregulation

SLITRK2 encodes a transmembrane protein that modulates neurite outgrowth and synaptic activities and is implicated in bipolar disorder. Here, we addressed its physiological roles in mice. In the brain, the Slitrk2 protein was strongly detected in the hippocampus, vestibulocerebellum, and precerebellar nuclei—the vestibular-cerebellar-brainstem neural network including pontine gray and tegmental reticular nucleus. Slitrk2 knockout (KO) mice exhibited increased locomotor activity in novel environments, antidepressant-like behaviors, enhanced vestibular function, and increased plasticity at mossy fiber–CA3 synapses with reduced sensitivity to serotonin. A serotonin metabolite was increased in the hippocampus and amygdala, and serotonergic neurons in the raphe nuclei were decreased in Slitrk2 KO mice. When KO mice were treated with methylphenidate, lithium, or fluoxetine, the mood stabilizer lithium showed a genotype-dependent effect. Taken together, Slitrk2 deficiency causes aberrant neural network activity, synaptic integrity, vestibular function, and serotonergic function, providing molecular-neurophysiological insight into the brain dysregulation in bipolar disorders

Quality of partogram monitoring at a primary health centre in Zambia

Background: the World Health Organization (WHO) recommends using a partogram to reduce maternal and neonatal mortality, especially in developing countries. Some previous studies conducted in African countries suggested that appropriate use of a partogram with standardised monitoring was associated with good labour outcomes. However, the compliance rates of recording differed among the monitoring items on the partogram and the quality of monitoring has not been examined adequately. Objective: to examine the compliance for each monitoring item on the WHO partogram and the quality of the monitoring. Design: a retrospective and observation study. Methods: a retrospective review of partograms (n=200) was undertaken in a health centre in Lusaka, Zambia. We excluded referral cases, admission with full dilatation, birth before arrival, childbirth within 30 minutes, and false labour. Finally, 125 partograms were examined to assess the recording compliance for each monitoring item. An observation study in the delivery room and interviews with midwives were also conducted to examine the quality of monitoring for labour. The research ethics committee of the Division of Health Sciences, Osaka University Graduate School of Medicine and the Biomedical Research Ethics Committee of the University of Zambia approved the study. Findings: the lowest recording rate of the frequency of uterine contractions at the time of admission was 69.6%. The highest compliance rates in the active phase were found for the descent of the fetal head and cervix dilatation at 97.6% and 97.3%, respectively. The lowest rate was found for the mother's pulse rate at 25.5%, whereas 27.1% of the women admitted in the latent phase were diagnosed as entering the active phase in the acceleration phase. In addition, the methods of abdominal palpation for assessing uterine contractions and intermittent feral heart rare monitoring were nor appropriate. Key conclusions and implications: Zambian midwives have acquired sufficient understanding regarding the usefulness of the WHO partogram. However, there were differences in the compliance rates for each monitoring item due to a lack of medical devices and inappropriate monitoring skill. To improve labour outcomes with the WHO partogram, it is necessary to improve the recording and compliance rates for each monitoring item, as well as to upgrade the quality of monitoring. (C) 2014 Elsevier Ltd. All rights reserved

Role of Rho in Salt-Sensitive Hypertension

A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive hypertension as key switches of intracellular signaling. Focusing on Rho, high salt intake in the central nervous system increases sodium concentrations of cerebrospinal fluid in salt-sensitive subjects via Rho/Rho kinase and renin-angiotensin system activation and causes increased brain salt sensitivity and sympathetic nerve outflow in BP control centers. In vascular smooth muscle cells, Rho-guanine nucleotide exchange factors and Rho determine sensitivity to vasoconstrictors such as angiotensin II (Ang II), and facilitate vasoconstriction via G-protein and Wnt pathways, leading to increased vascular resistance, including in the renal arteries, in salt-sensitive subjects with high salt intake. In the vascular endothelium, Rho/Rho kinase inhibits nitric oxide (NO) production and function, and high salt amounts further augment Rho activity via asymmetric dimethylarginine, an endogenous inhibitor of NO synthetase, causing aberrant relaxation and increased vascular tone. Rho-associated mechanisms are deeply involved in the development of salt-sensitive hypertension, and their further elucidation can help in developing effective protection and new therapies