Ixeris dentata (Thunb) Nakai attenuates cognitive impairment in MPTP-treated mouse model of Parkinson's disease

Purpose: To evaluate the cognition-enhancing effect of Ixeris dentata (Thunb) Nakai in a mouse model of Parkinson's disease (PD). Methods: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD was used to evaluate the effect of Ixeris dentata (IDE) extract on the alteration of behavioral responses using rotarod and passive avoidance tests. The effect of IDE on oxidative stress levels were analyzed based on superoxide dismutase (SOD) and catalase (CAT) enzyme levels, and lipid peroxidation (LPO) in brain tissues. Results: MPTP (20 mg/kg, ip)-induced mice resulted in a significant (p < 0.01) behavioral deficiencies in locomotor behavior (from 53.15 ± 1.01 to 23.56 ± 1.04) and cognitive functions (from 297 ± 2.47 to 201.17 ± 3.23 s) compared with their respective control groups. Administration of IDE (20, 40 and 80 mg/kg, po) for three weeks significantly and dose-dependently improved (p < 0.001 at 80 mg/kg) locomotor and cognitive deficits in MPTP- treated mice. IDE treatment also significantly (p < 0.01 at 80 mg/kg) inhibited decrease in superoxide dismutase and catalase enzyme activities, and lipid peroxides in MPTP-treated mice in brain tissues. Conclusion: IDE exhibits good protection against MPTP-induced behavioral deficits via potential antioxidant defense mechanisms. Therefore, IDE could potentially be developed as a therapeutic approach for the treatment of neurodegenerative diseases. Keywords: Ixeris dentata, Neurodegenerative disease, MPTP, Parkinson's disease, Oxidative stres

Characteristics of Ca Currents in Rabbit Basilar Arterial Smooth Muscle Cells

In order to determine the exact nature of Ca channels involved in various cerebrovascular contractile behaviour including vasospasm, we performed experiments to identify and characterize the types of Ca channels in rabbit basilar arterial smooth muscle cells by using kinetic and pharmacologic tools. Sngle smooth muscle cells were enzymatically isolated from rabbit basilar artery. Single cells were voltageclamped, and membrane currents were recorded using the whole-cell configuration of patch clamp technique. The measured cell capacitance (Cm) was 19.2 ± 0.65 pF ( n 21) and input resistance (Rmpu, ) was 2.04 ± 0.12 Gn(n 12), These passive membame properties are similar to other cerebraovascular smooth muscle cells. Inward Ca2 ' -channel current was recorded. Replacement of external Ca2+( 2 mM) with Ba" (10 mM) increased the amplitude of the current and did not shift the I-V relationship for lBa in comparison with that for Ie.. Changing the holding potential from -SO to -40 mV decreased the current amplitude but did not shift the voltage dependence. No detectable low-threshold, rapid inactivating inward current was observed. Steady-state activation and inactivation curves for lea(V, 210c') -4.4 mV; V, 2(inac,) -22.3 mV) and lBa(v, 2(oc') -7.5 mV; VI 2 {Inact } -20.5 mV) were determined. The theoritical 'window current's amplitude was calculated for lea and lBa• Calcium channel current was almost completely inhibited by l,uM nicardipine and enhanced by Bay K 8644, suggesting this is carried by 'L-type' but not by 'T-type' calcium channel. Bay K 8644 significantly shifted activation curve to the negative potential. Both 8-br-cAMPW.l ~ 1 mM) and 8-br-cGMP( 0.1 ~ 1 mM), a membrane permeable cyclic nucleotides, decreased the current amplitude. From the above results, it is suggested that only 'L-type' Ca-current(ICa_d exists in rabbit basilar arterial smooth muscle cells

Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats

Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. Although, Schisandrae Fructus was recently reported to attenuate the interleukin (IL)-1β-induced inflammatory response in chondrocytes in vitro, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. Therefore, we investigated the effects of the ethanol extract of Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that administration with SF had a tendency to attenuate MIA-induced damage of articular cartilage as determined by a histological grade of OA. SF significantly suppressed the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in MIA-induced OA rats. SF also effectively inhibited expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers for diagnosis and progression of OA, such as cartilage oligomeric matrix protein and C-telopeptide of type II collagen, were markedly ameliorated by SF administration. These findings indicate that SF could be a potential candidate for the treatment of OA

Effects of ProstagIand in F2a on the Spontaneous Contractions and Electrical Activities in the Circular Smooth MuscIe of the Guinea-Pig Stomach

Effects of PGF2a and indomethacin on the mechanical and electrical membrane properties of guinea-pig antral smooth muscle were studied using microeletrodes and tension recording technique and whole cell patch clamp technique. In this tissue, indomethacin inhibited the contractility and such an effect was reversed by PGF2a. PGF2a increased spontaneous contractions potently and the frequency and amplitudes of slow waves were also enhanced. PGF2a-induced contractions were not abolished by the pretreatment with nifedipine or by the nominal Ca2+-free condition but were abolished by pretreatment with La3+ or absolute Ca2+-free condition. Ionic currents were also measured by whole cell voltage clamp technique. PGF2a increased the size of voltage operated Ca2+ inward currents, and Ca-dependent K+ outward currents, but had no effect on sustained outward currents. From the above results, it is assumed that PGF2 a acts as an endogenous prostaglandin in the gastric antrum of the guinea-pig. PGF2a has promoting effects on electrical activities and such effects seem to contribute to the increase of contraction, but the greatest part of the increase of contraction is due to receptor-mediated increase of [Ca2+]i. Several possible mechanisms were suggested for the receptor-mediated [Ca2+]i increase

Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats

Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. Although, Schisandrae Fructus was recently reported to attenuate the interleukin (IL)-1β-induced inflammatory response in chondrocytes in vitro, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. Therefore, we investigated the effects of the ethanol extract of Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that administration with SF had a tendency to attenuate MIA-induced damage of articular cartilage as determined by a histological grade of OA. SF significantly suppressed the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in MIA-induced OA rats. SF also effectively inhibited expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers for diagnosis and progression of OA, such as cartilage oligomeric matrix protein and C-telopeptide of type II collagen, were markedly ameliorated by SF administration. These findings indicate that SF could be a potential candidate for the treatment of OA

Stent Thrombosis, Clinical Events, and Influence of Prolonged Clopidogrel Use After Placement of Drug-Eluting Stent Data From an Observational Cohort Study of Drug-Eluting Versus Bare-Metal Stents

ObjectivesThe purpose of this study was to evaluate the risk of stent thrombosis (ST), clinical outcomes, and the benefits of extended clopidogrel use after drug-eluting stent (DES) implantation.BackgroundData are limited regarding uniform evaluation of ST and the influence of clopidogrel continuation beyond 12 months on late events after DES treatment.MethodsWe identified 7,221 patients who received DES implantation (n = 3,160) or bare-metal stent (BMS) implantation (n = 4,061), and compared long-term adverse outcomes. Additionally, 2,851 patients with DES surviving 12 months without major events were analyzed according to clopidogrel continuation.ResultsThe adjusted-risk of overall ST was similar in the 2 groups. After 1 year, however, DES patients showed a higher risk of ST; definite/probable (hazard ratio [HR]: 3.55, 95% confidence interval [CI]: 1.26 to 9.99). The adjusted-risk of death (HR: 0.60, 95% CI: 0.46 to 0.79), death/myocardial infarction (HR: 0.63, 95% CI: 0.49 to 0.81), and target lesion revascularization (HR: 0.32, 95% CI: 0.24 to 0.43) were significantly lower in the DES group than in the BMS group. Continuing clopidogrel beyond 12 months was not associated with a reduced risk for ST (HR: 0.54, 95% CI: 0.07 to 4.23), death (HR: 1.20, 95% CI: 0.55 to 2.66), or death/myocardial infarction (HR: 1.16, 95% CI: 0.56 to 2.42) after DES implantation.ConclusionsAs compared with BMS, DES showed a similar risk of overall ST, but a higher risk of very late ST. The rates of death, death/myocardial infarction, and target lesion revasuclarization were significantly lower in the DES group. Clopidogrel continuation beyond 1 year did not appear to reduce ST and clinical events after DES implantation

Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus The DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients)

ObjectivesWe sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM).BackgroundAlthough cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients.MethodsThis randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months.ResultsThe 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 ± 0.53 mm vs. 0.38 ± 0.54 mm, p = 0.025) and in-segment (0.42 ± 0.50 mm vs. 0.53 ± 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR.ConclusionsTriple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients