Oryeongsan (Goreisan) Ameliorates Experimental Autoimmune Encephalomyelitis.

Objective Oryeongsan (Goreisan), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. Goreisan has been revealed to have anti-inflammatory actions and inhibit a water channel, the aquaporin (AQP). We herein report the therapeutic effect of Goreisan on experimental autoimmune encephalomyelitis (EAE in, an animal model of inflammatory demyelinating diseases. Materials and Methods EAE mice immunized with MOG35-55 peptide were divided into Goreisan- and sham-treated groups. The clinical EAE score and histopathological finding of the central nervous system (CNS) were analyzed. For the proliferation assay, prepared spleen cells from immunized mice were cultured and analyzed for the [3H]-thymidine uptake and cytokine concentrations of the culture supernatant. The relative quantification of AQP4 mRNA in the CNS of EAE mice was analyzed quantitatively. Results The EAE score of the Goreisan-treated mice was significantly lower than that of the sham-treated mice. The CD4-positive cell number in the CNS of Goreisan-treated mice was lower than that of sham-treated mice. In the recall response to MOG35-55 peptide, the cell proliferation did not differ markedly between the spleen cells from Goreisan- and sham-treated mice. Furthermore, Goreisan decreased the mRNA level of AQP4 in the spinal cord during EAE. Conclusion Goreisan prevented the disease activity of EAE by inhibiting the migration of pathogenic cells into the CNS by suppressing the AQP4 expression in the CNS. Goreisan may have a therapeutic effect on inflammatory demyelinating diseases.

Acupuncture and Laser Acupuncture as Treatments for Emotional Distress in Infertile Women in Japan.

Objectives: Needle and laser acupuncture are often used to improve the success rate of assisted reproductive technology (ART). This study examined whether needle or laser acupuncture ameliorated the emotional distress experienced by infertile women undergoing in vitro fertilization and embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI). Materials and Methods: Fifty-one infertile women who were undergoing IVF-ET or ICSI received needle acupuncture (needle-acupuncture group; n = 32) or laser acupuncture treatment (laser-acupuncture group; n = 19). The emotional distress experienced by the infertile women was evaluated using 2 questionnaires-the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI)-both before and after 3 months of treatment. Results: In the needle-acupuncture group, the POMS detected significant post-treatment reductions in tension/anxiety (P < 0.001), depression/dejection (P < 0.001), anger/hostility (P < 0.001), confusion (P < 0.05), and total mood disturbance (TMD; p < 0.001). However, the POMS scores for vigor/activity and fatigue were not altered significantly after the treatment. In the STAI, both State and Trait scores had significantly decreased after the acupuncture (P < 0.001 and P < 0.05, respectively). In the laser-acupuncture group, the POMS detected significantly lower tension/anxiety (P < 0.05) and vigor/activity (P < 0.05) scores after the treatment. However, the POMS did not detect significant changes in depression/dejection, anger/hostility, fatigue, confusion, or TMD after the treatment. Furthermore, neither the STAI-State nor the STAI-Trait score had significantly decreased after the laser acupuncture treatment. Conclusions: These results indicate that needle and laser acupuncture ameliorate the emotional distress experienced by women who are undergoing IVF-ET or ICSI.

ß-carotene reverses the IL-1ß-mediated reduction in paraoxonase-1 expression via induction of the CaMKKII pathway in human endothelial cells.

Interleukin-1 beta (IL-1ß) induces endothelial dysfunction and reduces nitric oxide (NO) production. IL-1ß also enhances adhesion molecule expression and induces arteriosclerosis. Conversely, high-density lipoprotein (HDL) induces endothelial NO synthase (eNOS), paraoxonase-1 (PON-1) activity, and maintains vascular health. Diet-derived ß-carotene prevents arteriosclerosis, but its mode of action is not understood. The purpose of this study was to examine the HDL-like mechanisms of ß-carotene in endothelial cells. We added IL-1ß and/or ß-carotene to cultured human endothelial cells and examined its effects on the regulation of HDL signal transduction pathways using RT-PCR, real-time PCR, Western blot (WB), and endothelial-U937 adhesion analysis. IL-1ß decreased the expression of Ca2+/calmodulin-dependent kinase II (CaMKII), eNOS, PON-1, phosphatidylinositol 3-kinase (PI3K), PSD-95/Dlg/ZO-1 (PZK1), and liver kinase B1 (LKB1). Conversely, it increased the expression of intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein 1 (MCP-1). In contrast, ß-carotene increased the expression of CaMKKII, PI3K, PZK1, LKB1, eNOS, PON-1, and reduced the expression of ICAM-1 and MCP-1. ß-carotene also induced phospho-AMP-activated protein kinase (p-AMPK), phospho-eNOS and PON-1 proteins. Importantly, ß-carotene upregulated the IL-1ß-mediated decrease of CaMKKII, PZK1, LKB1, eNOS and PON-1. ß-carotene inhibited IL-1ß-mediated cell adhesion of U937 to endothelial cells. The effect of ß-carotene was reversed by a CaMKK inhibitor, STO-609. These findings indicate that ß-carotene regulates the expression of PON-1, eNOS and adhesion molecules via CaMKK pathway activation. ß-carotene may contribute to the functional maintenance of vascular endothelial cells in a manner similar to HDL, protecting them against stimuli such as IL-1ß.

PET study of brain acetylcholinesterase in cerebellar degenerative disorders.

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.

Effects of long-term administration of HMG-CoA reductase inhibitor, atorvastatin, on stroke events and local cerebral blood flow in stroke-prone spontaneously hypertensive rats.

The objective of this study was to determine whether the long-term administration of an HMG-CoA reductase inhibitor, atorvastatin, confers protective effects against stroke events in stroke-prone spontaneously hypertensive rats (SHRSPs). Atorvastatin (2 mg/kg, 20 mg/kg) or vehicle was orally administered to 8-week-old SHRSPs for 11 weeks. The survival ratio and stroke incidence were calculated, and plasma lipids and plasma levels of asymmetric dimethylarginine (ADMA), a circulating endogenous competitive inhibitor of NO synthase, were measured after sacrifice. The effect of atorvastatin on local cerebral blood flow (l-CBF) was also determined in 13-week-old SHRSPs after treatment with 20 mg/kg atorvastatin daily for 5 weeks. The survival ratios at 19 weeks of age were 15, 30, and 50% in the vehicle, low-dose (2 mg/kg), and high-dose groups (20 mg/kg), respectively. The survival ratio was significantly higher in the high-dose group than in the vehicle group. The incidence of stroke was significantly lower in the high-dose group than in the vehicle group. The levels of ADMA were 0.81+/-0.18 (mean+/-S.D.), 0.62+/-0.09, and 0.61+/-0.06 micromol/l in the vehicle, low-dose, and high-dose groups, respectively. Atorvastatin administration significantly reduced the ADMA levels without affecting the levels of plasma lipids. The level of l-CBF tended to be higher in the treated group, but not to a significant extent. Thus, atorvastatin was determined to confer a protective effect against hypertension-based stroke. The data suggest that the efficacy of the statin for stroke protection may be partially involved in the improvement of endothelial function via NO production and reduction of ADMA. Statins may confer useful protection against not only atherosclerosis-based stroke, but also hypertension-based stroke.

Intussusception of the small bowel associated with nephrotic syndrome.

We report the case of a 2-year-old boy who developed a small bowel intussusception during treatment failure of his first episode of nephrotic syndrome. Despite the absence of typical symptoms other than abdominal pain, the intussusception was diagnosed by ultrasonography and computed tomography and successfully reduced by air enema. No pathological lead point was discovered, and no symptoms of Henoch-Schönlein purpura developed later. Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema. Ultrasonography or computed tomography should be performed, even in the absence of other typical symptoms suggestive of intussusception. We should also bear in mind that the intussusception associated with nephrotic syndrome might occur at regions other than the typical ileocolic region, such as within the small intestine.