Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice.

Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via i.p. injection for five consecutive days to induce the mouse model of PD. Paeonol (20 mg/kg) was administrated orally for 21 days. Behavior was assessed using the rotarod performance and open­field tests. Additionally, the levels of tyrosine hydroxylase (TH), microglia, interleukin­1ß (IL­1ß), and brain­derived neurotrophic factor (BDNF) in the substantia nigra pars compacta (SNpc) were evaluated by immunohistochemical staining. MPTP/p­induced motor deficits were observed to be significantly improved following long­term treatment with paeonol. Paeonol treatment decreased MPTP/p­induced oxidative stress, as determined by evaluating the activity levels of superoxide dismutase, catalase and glutathione. Additionally, MPTP/p­induced neuroinflammation was assessed by examining the levels of microglia and IL­1ß, which were significantly decreased following paeonol treatment. Paeonol treatment improved the MPTP/p­induced dopaminergic neurodegeneration, as measured by observing the increased TH level in the SNpc. Furthermore, the BDNF level was significantly elevated in the paeonol treatment group compared with mice treated with MPTP/p only. In conclusion, paeonol exerted therapeutic effects in the MPTP/p­induced mouse model of PD, possibly by decreasing the damage from oxidative stress and neuroinflammation, and by enhancing the neurotrophic effect on dopaminergic neurons. The results demonstrate paeonol as a potential novel treatment for PD.

[Case-control study on influence factors of birth defects].

OBJECTIVE: To investigate the influence factors of birth defects. METHODS: The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.). The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. RESULTS: (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6.034‰. The top six defect diseases were congenital heart disease (112 cases), total harelip (cleft lip; cleft lip with palate: 85 cases), polydactyly (53 cases), neural tube defects (38 cases), congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48%, 353/648). (2) Their mother education level in the birth-defect group (25.6%) were significantly lower than that in control group (30.0%, P<0.05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P<0.05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20.5%, respectively) was higher than that in control group (1.1% and 11.7%, respectively), the difference between which were significant (P<0.01). The rate of disease (34.3%), fever (13.1%), taking drugs (33.8%) in pregnancy period in birth defect group were higher than that in control group (13.5%, 1.5% and 9.9%, respectively), the difference between which were significant (P<0.01). The rate of bad moral irritation to the mother in pregnancy in birth defect group (11.3%) was significantly higher than that in control group (1.4%, P<0.01). (5) There were 19 cases (2.9%, 19/648) with family heredity medical history in birth defect group, but there were none in the control group, the difference between which were significant (P<0.01). There were 89 cases (13.7%, 89/648) with unusual birth history of their mothers in birth defect group, but there were 31 cases (4.8%, 31/650) in control group, the difference between which were significant (P<0.01). (6) Conditional Logistic Regression model was used for univalent and multivariate analysis. The results showed that main influence factors were identified as having important effect on birth defects, including mothers' exposure to harmful chemical factors (OR=13.46), disease (OR=3.37), taking drugs (OR=2.20), exposure to bad moral irritation (OR=5.44), food-choosy (OR=1.90), anemia (OR=1.52) in gestational period, polyembryony (OR=4.40), father drinking (OR=1.55). While it was protective factors to supplement microelements such as the calcium iron and nutrient, etc.in pregnancy period (OR=0.45). CONCLUSIONS: First, the main birth defects were congenital heart disease, total harelip(cleft lip; cleft lip with palate), polydactyly, neural tube defects, congenital hydrocephalus and limb reduction defect in turn. Second, the main influence factors identified as having important effect on birth defects were mothers' exposure to harmful chemical factors, ill, taking drugs, exposure to bad moral irritation, food-choosy, anemia in gestational period, polyembryony, father drinking. But it is protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period. Finally, it is the important part to prevent the birth defects by reducing and controlling dangerous factors in pregnancy period.

Stable expression and functional characterization of a human nicotinic acetylcholine receptor with α6ß2 properties: discovery of selective antagonists.

BACKGROUND AND PURPOSE: Despite growing evidence that inhibition of α6ß2-containing (α6ß2*) nicotinic acetylcholine receptors (nAChRs) may be beneficial for the therapy of tobacco addiction, the lack of good sources of α6ß2*-nAChRs has delayed the discovery of α6ß2-selective antagonists. Our aim was to generate a cell line stably expressing functional nAChRs with α6ß2 properties, to enable pharmacological characterization and the identification of novel α6ß2-selective antagonists. EXPERIMENTAL APPROACH: Different combinations of the α6, ß2, ß3, chimeric α6/3 and mutant ß3(V273S) subunits were transfected in human embryonic kidney cells and tested for activity in a fluorescent imaging plate reader assay. The pharmacology of rat immune-immobilized α6ß2*-nAChRs was determined with ¹²5I-epibatidine binding. KEY RESULTS: Functional channels were detected after co-transfection of α6/3, ß2 and ß3(V273S) subunits, while all other subunit combinations failed to produce agonist-induced responses. Stably expressed α6/3ß2ß3(V273S)-nAChR pharmacology was unique, and clearly distinct from α4ß2-, α3ß4-, α7- and α1ß1δε-nAChRs. Antagonist potencies in inhibiting α6/3ß2ß3(V273S) -nAChRs was similar to their binding affinity for rat native α6ß2*-nAChRs. Agonist affinities for α6ß2*-nAChRs was higher than their potency in activating α6/3ß2ß3(V273S)-nAChRs, but their relative activities were equivalent. Focussed set screening at α6/3ß2ß3(V273S)-nAChRs, followed by cross-screening with the other nAChRs, led to the identification of novel α6ß2-selective antagonists. CONCLUSIONS AND IMPLICATIONS: We generated a mammalian cell line stably expressing nAChRs, with pharmacological properties similar to native α6ß2*-nAChRs, and used it to identify novel non-peptide, low molecular weight, α6ß2-selective antagonists. We also propose a pharmacophore model of α6ß2 antagonists, which offers a starting point for the development of new smoking cessation agents.

Zinc overload enhances APP cleavage and Aß deposition in the Alzheimer mouse brain.

BACKGROUND: Abnormal zinc homeostasis is involved in ß-amyloid (Aß) plaque formation and, therefore, the zinc load is a contributing factor in Alzheimer's disease (AD). However, the involvement of zinc in amyloid precursor protein (APP) processing and Aß deposition has not been well established in AD animal models in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, APP and presenilin 1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced amyloidogenic APP cleavage and Aß deposition, and impaired spatial learning and memory in the transgenic mice. We further examined the effects of zinc overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc enhancement of APP expression and cleavage was further confirmed in vitro. CONCLUSIONS/SIGNIFICANCE: The present data indicate that excess zinc exposure could be a risk factor for AD pathological processes, and alteration of zinc homeostasis is a potential strategy for the prevention and treatment of AD.

[Effect of acupuncture on rehabilitation training of child's autism].

OBJECTIVE: To observe the effect of acupuncture on rehabilitation training for children's autism. METHODS: Forty autistic children receiving rehabilitation training were divided into a control group and a treatment group, 20 cases in each group. The control group received rehabilitation training including ABA training, the Conductive Education Approach and the training of sensory integration, about 90 sessions for each training; the treatment group received acupuncture treatment for 60-90 sessions after the rehabilitation training. Their results were detected by the revised Chinese version of Psycho-Educational Profile for autistic and developmentally disabled children (C-PEP). RESULTS: The markedly effective rate was 55.0% in the treatment group and 15.0% in the control group with a very significant difference between the two groups (P < 0.01); the differences before and after training in some projects such as the total score of development, imitation, oral cognition in the treatment group were very significantly different from those in the control group (P < 0.01). CONCLUSION: Acupuncture combined with scientific and effective rehabilitation training has a better therapeutic effect than that of the simple rehabilitation training for child's autism.

[On effects of acupoints and drugs in acupoint-injection treatment].

Acupoint-injection therapy is a successful sample for clinical application of integrated Chinese and Western medicine, and has widely been applied clinically. In this method, effects of meridians, acupoints and drugs are organically combined, with obviously higher total therapeutic effect compared with routine acupuncture and moxibustion, intermuscular injection or intravenous injection. In this paper, the total therapeutic effects of acupoint-injection, high effectiveness of drugs and integrated action of acupoint and drug were discussed mainly and it is considered that the basic reason of acupoint-injection producing the high effect of drug is due to meridians and acupoints integrating some pharmacological actions of drugs.