Monitoring the autonomic nervous activity as the objective evaluation of music therapy for severely and multiply disabled children

Severely and multiply disabled children (SMDC) are frequently affected in more than one area of development, resulting in multiple disabilities. The aim of the study was to evaluate the efficacy of music therapy in SMDC using monitoring changes in the autonomic nervous system, by the frequency domain analysis of heart rate variability. We studied six patients with SMDC (3 patients with cerebral palsy, 1 patient with posttraumatic syndrome after head injury, 1 patient with herpes encephalitis sequelae, and 1 patient with Lennox-Gastaut syndrome characterized by frequent seizures, developmental delay and psychological and behavioral problems), aged 18-26 (mean 22.5 ± 3.5). By frequency domain method using electrocardiography, we measured the high frequency (HF; with a frequency ranging from 0.15 to 0.4 Hz), which represents parasympathetic activity, the low frequency/high frequency ratio, which represents sympathetic activity between the sympathetic and parasympathetic activities, and heart rate. A music therapist performed therapy to all patients through the piano playing for 50 min. We monitored each study participant for 150 min before therapy, 50 min during therapy, and 10 min after therapy. Interestingly, four of 6 patients showed significantly lower HF components during music therapy than before therapy, suggesting that these four patients might react to music therapy through the suppression of parasympathetic nervous activities. Thus, music therapy can suppress parasympathetic nervous activities in some patients with SMDC. The monitoring changes in the autonomic nervous activities could be a powerful tool for the objective evaluation of music therapy in patients with SMDC.     

Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest

Aim To investigate the association between regional brain oxygen saturation (rSO₂) on hospital arrival and neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest (OHCA).Methods A prospective cohort study was conducted, registering 179 patients with OHCA who were referred to Senri Critical Care Medical Centre between April 2009 and June 2010. Of these patients, 92 met the inclusion criteria. The primary end point was “neurological outcomes” at hospital discharge according to the “Utstein style” guidelines.Results The overall rate of good neurological outcome at hospital discharge was 14% (n = 13). Sixty-one patients with rSO₂ ≤25% showed poor neurological outcome in the receiver operating curve analysis (optimal cut-off point, 25%; sensitivity, 0.772; specificity, 1.000; positive predictive value, 1.000; area under the curve (AUC), 0.919; p < 0.0001). The AUC for rSO₂ was greater than that for base excess (p = 0.0461) or lactate (p = 0.0128) measured on hospital arrival. Since rSO₂ >40% was previously collated with good neurological outcome after cardiovascular surgery, we categorised our patients into three groups in a post hoc analysis: patients with rSO₂ ≤25% (n = 61); patients with rSO₂ 26-40% (n = 9) and patients with rSO₂ >40% (n = 22). Patients with good neurological outcome were as follows: 0 (0%)/61 with rSO₂ ≤25%; two (22.2%)/9 with rSO₂ 26-40% and 11 (50.0%)/22 with rSO₂ >40% (p < 0.0001).Conclusion rSO₂ on hospital arrival may help predict neurological outcomes at hospital discharge in patients with OHCA.     

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice

OBJECTIVE:

To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors.

MATERIALS AND METHODS:

The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice.

RESULTS:

After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions.

CONCLUSIONS:

Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.     

Canine Oral Mucosal Fibroblasts Differentiate into Osteoblastic Cells in Response to BMP‐2

Several lines of evidence show that transplantation of osteoblastic cells or genetically engineered nonosteogenic cells expressing osteoblast‐related genes into bone defects effectively promotes bone regeneration. To extend this possibility, we investigated whether oral mucosal fibroblasts are capable of differentiating into osteoblastic cells by conducting in vitro and in vivo experiments. We investigated the effects of bone morphogenetic protein‐2 (BMP‐2) on osteoblast differentiation of cultured fibroblasts isolated from canine buccal mucosa. We also transplanted green fluorescence protein (GFP)‐expressing fibroblasts with gelatin/BMP‐2 complexes into the subfascial regions of athymic mice, and investigated the localization of GFP‐positive cells in the ectopically formed bones. The cultured canine buccal mucosal fibroblasts differentiated into osteoblastic cells by increasing their alkaline phosphatase (ALP) activity and Osteocalcin, Runx2, and Osterix mRNA expression levels in response to BMP‐2. Transplantation experiments of GFP‐expressing oral mucosal fibroblasts with gelatin/BMP‐2 complexes revealed that 17.1% of the GFP‐positive fibroblasts differentiated into ALP‐positive cells, and these cells accounted for 6.2% of total ALP‐positive cells in the ectopically formed bone. This study suggests that oral mucosal fibroblasts can differentiate into osteogenic cells in response to BMP‐2. Thus, these cells are potential candidates for cell‐mediated bone regeneration therapy in dentistry. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Oxygen levels epigenetically regulate fate switching of neural precursor cells via hypoxia-inducible factor 1α-notch signal interaction in the developing brain

Oxygen levels in tissues including the embryonic brain are lower than those in the atmosphere. We reported previously that Notch signal activation induces demethylation of astrocytic genes, conferring astrocyte differentiation ability on midgestational neural precursor cells (mgNPCs). Here, we show that the oxygen sensor hypoxia-inducible factor 1α (HIF1α) plays a critical role in astrocytic gene demethylation in mgNPCs by cooperating with the Notch signaling pathway. Expression of constitutively active HIF1α and a hyperoxic environment, respectively, promoted and impeded astrocyte differentiation in the developing brain. Our findings suggest that hypoxia contributes to the appropriate scheduling of mgNPC fate determination.     

Coronavirus infection of rat dorsal root ganglia: ultrastructural characterization of viral replication, transfer, and the early response of satellite cells

Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum-Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells.