[Electroacupuncture Intervention Inhibits the Decline of Learning-memory Ability and Overex- pression of Cleaved Caspase-3 and Bax in Hippocampus Induced by Isoflurane in APPswe/PS 1].

OBJECTIVE: To investigate the protection mechanism of electroacupuncture (EA) therapy against Alzheimer's disease (AD)-like neurotoxicity induced by Isoflurane. METHODS: Twenty-four APPswe/PS 1 dE9 double transgenic mice (one of the most extensively used transgenic mouse model of AD) and 24 littermate wild-type mice were randomly assigned into control (Con) group, isoflurane (Iso) group and EA group, respectively (n = 8 in each group). EA (2 Hz/100 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Yongquan" (KI 1) for 15 min, once a day for 3 days. The transgenic mice were exposed to a closed box filled with 1.2% isoflurane + 30% O2 +70% N2 for 4 h. The animals' learning-memory ability was detected by Morris water maze test. The expression of cleaved Caspase-3 in the CA 1 area of hippocampus was detected by immunohistochemistry, and that of hippocampal Bcl-2 and Bax proteins detected by Western blot. RESULTS: Compared with the wilde-type mice, the average escape latency of place navigation test was significantly longer, while the percentage of target-quadrant stay time and the target- platform crossing times of spacial probe test were marked decreased in AD + lso mice (P < 0.05). After acupuncture intervention, the abovementioned changes were reversed (P < 0.05). Correspondingly, compared with the AD-Con group, the number of hippocampal activated Caspase-3-positive cells and the expression of Bax protein were significantly increased in the AD-Iso group (P < 0.05). After EA intervention, the increased Caspase-3-positive cell number and Bax protein expression were remarkably down-regulated in the AD-EA group, and the decreased ratio of Bcl-2/Bax in AD-Iso mice was obviously up-regulated in AD-EA mice (P < 0.05). No significant changes were found in the average escape latency, the percentage of target-quadrant stay time and the target-platofrm corssing times, and inthe number of hippocampal activated Caspase-3-positive cells, the expression levels of hippocampal Bcl-2 and Sax and the ratio of Bcl-2/Bax in the three groups of wilde-type mice (P > 0.05). CONCLUSION: EA intervention can improve the learning-memory ability in AD + Isoflurane mice, suggesting a reduction of AD-like neurotoxicity, which may be associated with its actions in inhibiting the overexpression of activated Caspase-3 and Bax proteins in the hippocampus.

MITF-siRNA formulation is a safe and effective therapy for human melasma.

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor-siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.

Ginkgo biloba extract (EGb 761) attenuates lung injury induced by intestinal ischemia/reperfusion in rats: roles of oxidative stress and nitric oxide.

AIM: To investigate the effect of ginkgo biloba extract (EGb 761) on lung injury induced by intestinal ischemia/reperfusion (II/R). METHODS: The rat model of II/R injury was produced by clamping the superior mesenteric artery for 60 min followed by reperfusion for 180 min. The rats were randomly allocated into sham, II/R, and EGb + II/R groups. In EGb + II/R group, EGb 761 (100 mg/kg per day) was given via a gastric tube for 7 consecutive days prior to surgery. Rats in II/R and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung injury was assessed by light microscopy, wet-to-dry lung weight ratio (W/D) and pulmonary permeability index (PPI). The levels of malondialdehyde (MDA) and nitrite/nitrate (NO2(-)/NO3(-)), as well as the activities of superoxide dismutase (SOD) and myeloperoxidase (MPO) were examined. Western blot was used to determine the expression of inducible nitric oxide synthase (iNOS). RESULTS: EGb 761 markedly improved mean arterial pressure and attenuated lung injury, manifested by the improvement of histological changes and significant decreases of pulmonary W/D and PPI (P < 0.05 or 0.01). Moreover, EGb 761 markedly increased SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation accompanied by down-regulation of iNOS expression (P < 0.05 or 0.01). CONCLUSION: The results indicate that EGb 761 has a protective effect on lung injury induced by II/R, which may be related to its antioxidant property and suppressions of neutrophil accumulation and iNOS-induced NO generation. EGb 761 seems to be an effective therapeutic agent for critically ill patients with respiratory failure related to II/R.

Pharmacokinetics of single-dose levonorgestrel in adolescents.

PURPOSE: The purpose of this study is to compare the pharmacokinetics of levonorgestrel, a drug used for emergency contraception between female adolescents and adults. METHODS: Twenty-two female subjects, aged 13-16 years, received a single 0.75-mg dose of the drug. Serial blood samples were collected for 72 h and used to measure plasma levonorgestrel concentrations. Previously published data from 16 adults, aged 18-45 years, served as comparison. RESULTS: There was a statistically significant higher total plasma clearance divided by the bioavailability (CL/F) of levonorgestrel in adolescents compared to adults, resulting in lower maximum and average total plasma concentrations. There was a trend for a larger volume of distribution divided by bioavailability (V/F), but there was no significant difference in the half-life of levonorgestrel in adolescents relative to adults (p=.098). CONCLUSION: The differences between adolescents and adults are unlikely to be clinically significant because specific changes in total concentrations suggest that unbound concentrations are probably not affected. Furthermore, empirically high doses of levonorgestrel are given for emergency contraception.

Neuroprotective properties of catalpol in transient global cerebral ischemia in gerbils: dose-response, therapeutic time-window and long-term efficacy.

The present study evaluated for the first time the dose-effectiveness, therapeutic time-window and long-term efficacy of the neuroprotection of catalpol by behavioral and histological measures in gerbils subjected to transient global cerebral ischemia. Catalpol (1 mg/kg ip) used immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h significantly rescued neurons in the hippocampal CA1 subfield and reduced cognitive impairment. The neuroprotective efficacy of catalpol became more evident at the doses of 5 and 10 mg/kg. Of great importance were the findings that the neuroprotective efficacy of catalpol still could be seen even when the treatment was delayed 3 h and when the observational period was lasted out 35 days after ischemia. It was reasonable to draw the conclusion that catalpol was truly neuroprotective rather than simply delayed the onset of neuronal damage. These results suggested that catalpol might be of therapeutic value for global cerebral ischemia.

Neuroprotection of catalpol in transient global ischemia in gerbils.

The neuroprotection of catalpol and its mechanism was evaluated in cerebral ischemic model in gerbils. Three groups were designed as sham-operated, ischemia-treated, respectively, with catalpol and saline. Catalpol was injected intraperitoneally immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h with the dose of 5.0 mg/kg. The neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in Y-maze and the survival neurons in CA1 subfield were counted under a microscope after behavioral testing. In addition, apoptosis induced by ischemia was also examined by using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling method. It was shown that catalpol significantly attenuated apoptosis, rescued hippocampal CA1 neurons and reduced cognitive impairment. In order to make clear the mechanism of catalpol's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase together with the content of lipid peroxide in cortex and hippocampus were assayed. The results proved that catalpol significantly reduced the content of lipid peroxide, increased the activity of glutathione peroxidase and decreased the activity of nitric oxide synthase. All these suggested that catalpol was a potential neuroprotective agent and its neuroprotective effects were achieved at least partly by promoting endogenous antioxidant enzymatic activities and reducing the formation of nitric oxide.