Furocoumarins from Angelica dahurica with hepatoprotective activity on tacrine-induced cytotoxicity in Hep G2 cells

Fractionation of the MeOH extract of Angelica dahurica Benth et Hook resulted in the isolation of six furocoumarins, imperatorin (1), isoimperatorin (2), (+/-)-byakangelicol (3), (+)-oxypeucedanin (4), (+)-byakangelicin (5), and (+)-aviprin (6). Among these, compounds 1 and 5 exhibited strong hepatoprotective activities, displaying EC(50) values of 36.6 +/- 0.98 and 47.9 +/- 4.6 microM, respectively. Compounds 3 and 4 showed moderate activities with EC(50) values of 112.7 +/- 5.35 and 286.7 +/- 6.36 microM, respectively. Silybin as a positive control showed the EC(50) value with 69.0 +/- 3.4 microM. Comparison of hepatoprotective activities for six furocoumarins 1 - 6 suggested that oxy-substitution at the C-9 position increased the hepatoprotective activity.     

Inhibitory activity of diacylglycerol acyltransferase by tanshinones from the root of Salvia miltiorrhiza

The inhibitory activity of tanshinones from Salvia miltiorrhiza was tested on rat liver diacylglycerol acyltransferase (DGAT). Cryptotanshinone (1) and 15,16-dihydrotanshinone I (3) exhibited potent DGAT inhibitory activities dose-dependently with IC50 values of 10.5 microg/ml and 11.1 microg/ml. However, tanshinone IIA (2) and tanshinone I (4) showed very weak inhibition (IC50 value: > 250 microg/ml). A dihydrofuran moiety was seemed to be responsible for the stronger inhibitory activity.     

Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices

1. The mechanism of stimulation of noradrenaline (NA) release by nicotine (NIC) was investigated in human cerebral cortex slices preloaded with 3H-noradrenaline. 2 NIC (10-1000 micro M) increased 3H-NA release in a concentration-dependent manner. 3. NIC (100 micro M)-evoked 3H-NA release was largely dependent on external Ca2+, and was attenuated by omega-conotoxin GVIA (0.1 micro M) but not by nitrendipine (1 micro M). 4. Tetrodotoxin (1 micro M) and nisoxetine (0.1 micro M) attenuated the NIC (100 micro M)-evoked release of 3H-NA. 5. Mecamylamine (10 micro M), dihydro-beta-erythroidine (10 micro M) and d-tubocurarine (30 micro M), but not alpha-bungarotoxin (alpha-BTX, 0.1 micro M), attenuated the NIC (100 micro M)-evoked release of 3H-NA. 6. NIC (100 micro M)-evoked release of 3H-NA was not affected by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 micro M) and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 100 micro M), but attenuated by MK-801 (10 micro M). MK-801 (0.1-1000 micro M) displaced the specific binding of 3H-nisoxetine with K(i) values of 91.2 micro M. NIC (100, 300 and 1000 micro M) did not induce 3H-D-aspartate release in human cerebral cortex slices. 7. NIC (100 micro M)-evoked release of 3H-NA was attenuated by 7-nitroindazole (10 micro M), N(G)-nitro-L-arginine methyl ester HCl (L-NAME, 30 micro M), N(G)-monomethyl-L-arginine acetate (L-NMMA, 300 micro M). [(3)H]-NA release induced by NIC (100 micro M) was attenuated by methylene blue (3 micro M) and 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ, 10 micro M), and enhanced by zaprinast (30 micro M). 8. In conclusion, NIC stimulates the release of 3H-NA through activation of alpha-BTX-insensitive nicotinic acetylcholine receptors in the human cerebral cortex slices and this action of NIC is associated with modulation of the NO/cGMP pathway.     

Blood-brain barrier disruption following the internal carotid arterial perfusion of alkyl glycerols

Non ionic, amphipathic molecules form vesicles and this property correlates with the disruption of membranes. In the present studies, high mM concentrations of aliphatic alcohols, 1-O-hexyldiglycerol (HDG) and 1-O-heptyltriglycerol (HTG), are shown to cause enhanced drug transport into brain via disruption of the blood-brain barrier (BBB) in vivo, as determined with an internal carotid artery perfusion method. The intravenous administration of comparable concentrations of HDG or HTG caused no increase in BBB transport of drug. The enhanced transport of drug showed a dependency on molecular weight as 45 mM HTG increased the transport of sucrose, 360 Da, but did not increase the transport of arginine vasopressin (AVP), 1084 Da, although AVP transport across the BBB was increased by 80 mM HDG or HTG. Quasielastic light scattering measurements provided evidence for the formation of vesicular structures in aqueous solutions containing high mM concentrations of the HDG or HTG. In summary, these studies demonstrate BBB disruption following the internal carotid arterial infusion of high mM concentrations of membrane active alkyl glycerols.     

Immunotoxic effects of 2-bromopropane in male Sprague-Dawley rats: a 28-day exposure study

Immunotoxic effects of 2-bromopropane were investigated in male Sprague-Dawley rats. The rats were treated orally daily with 2-bromopropane at 100, 330, or 1000 mg/kg for 28 consecutive days. Four days before necropsy, the rats were immunized intravenously with sheep red blood cells (SRBCs). The body and thymus weights were significantly reduced by treatment with 2-bromopropane at the highest dose. In addition, the numbers of splenic and thymic cells were decreased by 2-bromopropane. In hematology, the numbers of white blood cells, red blood cells, and platelets were significantly reduced. Among the serum clinical parameters, the levels of chloride ion were significantly increased by 2-bromopropane. The antibody response to SRBCs was significantly suppressed at the highest dose. With immunized animals, immunophenotyping of splenic and thymic cells was performed to investigate the changes of the number of macrophages, B cells, and T cells in spleen and the number of CD4+ and CD8+ cells in thymus. The numbers of most cell types were significantly decreased in the spleen when animals were treated with 2-bromopropane at 1,000 mg/kg. Likewise, all cell types of thymus were significantly decreased by 2-bromopropane. The present results suggest that 2-bromopropane may have an immunotoxic potential in male Sprague-Dawley rats when the rats are exposed for 28 d.     

Inhibition of TNF-alpha,IL-1beta,and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide,an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae)

Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae), was found to inhibit the productions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and the activation of nuclear factor kappaB (NF-kappaB) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Catalposide also inhibited the expressions of TNF-alpha, IL-1beta, and IL-6 genes and the nuclear translocation of p65 subunit of NF-kappaB in LPS-activated RAW 264.7 cells. Flow cytometric analysis revealed that catalposide suppressed the binding of FITC-conjugated LPS to CD14 on the surface of cells, probably resulting in the inhibitory effects on TNF-alpha, IL-1beta, and IL-6 productions and NF-kappaB activation. These findings suggest that catalposide could be an attractive candidate for adjunctive therapy in gram-negative bacterial infections.     

Effects of Qi-training on heart rate variability

This study investigates changes in autonomic nervous function through Qi-training. The power spectrum of heart rate variability (HRV) was examined in 20 sedentary healthy subjects and 20 Qi-trainees. It was found that Qi-training in healthy young subjects during controlled respiration increases the high frequency (HF) power and decreases the low frequency/high frequency (LF/HF) power ratio of HRV. These results support the hypothesis that Qi-training increases cardiac parasympathetic tone. In addition, Qi-trainees were found to have higher parasympathetic heart modulation compared with their age-matched, sedentary counterparts. This augmented HRV in Qi-trainees provides further support for long-term Qi-training as a possible non-pharmacological cardio-protective maneuver. In conclusion, Qi-training may stabilize the autonomic nervous system by modulating the parasympathetic nervous system.     

Diffusion-weighted MR findings in isolated angiitis of the central nervous system (IACNS)

OBJECTIVES: To describe the diffusion-weighted MR (DWI) findings of isolated angiitis of the central nervous system (IACNS) and narrow the differential diagnosis. METHODS: The DWI findings of two IACNS patients. Apparent diffusion coefficient (ADC) values were measured in the abnormal lesions, and DWI and T2-weighted MR images were visually inspected. RESULTS: IACNS was diagnosed based on clinical history, MR findings and cerebral angiographic findings. DWI showed hyperintense lesions with heterogeneous ADC values (287-1359 x 10(-6) mm2/s), which indicate the coexistence of cytotoxic and vasogenic oedema. CONCLUSIONS: The findings suggest that the various stages of inflammatory process with ischaemia might exist in IACNS and allow a differentiation from the usual arterial ischaemic infarction. DWI with ADC map can be a useful non-invasive diagnostic test increasing specificity in the diagnosis of IACNS, combined with conventional MRI and cerebral angiography.     

Steroidogenic acute regulatory protein expression in the normal human brain and intracranial tumors

In this study we found the expression of steroidogenic acute regulatory protein (StAR) mRNA and protein in both the normal human brain and intracranial tumors, using RT-PCR and immunohistochemistry. StAR mRNA is expressed at a very low level in the white matter of the normal human brain, but in tumoral tissues StAR mRNA was specifically expressed in oligodendrogliomas and malignant glial tumors. StAR-positive cells were also detected in the normal human brains and gliomas; its frequency and density were higher in glioma tissue. These findings suggest that StAR expression might be correlated with the growth of glial tumors.     

Idiopathic normal pressure hydrocephalus predominantly with prolonged fever and hyponatremia

Described is a patient with hydrocephalus and a gait disorder with associated prolonged fever and hyponatremia. The authors made a diagnosis of normal pressure hydrocephalus (NPH) and performed a ventriculoperitoneal shunt, which improved the gait disturbance, accompanied by resolution of the fever and hyponatremia.