Protection against kainate neurotoxicity by ginsenosides: attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress

We previously demonstrated that kainic acid (KA)-mediated mitochondrial oxidative stress contributed to hippocampal degeneration and that ginsenosides attenuated KA-induced neurotoxicity and neuronal degeneration. Here, we examined whether ginsenosides affected KA-induced mitochondrial dysfunction and oxidative stress in the rat hippocampus. Treatment with ginsenosides attenuated KA-induced convulsive behavior dose-dependently. KA treatment increased lipid peroxidation and protein oxidation and decreased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the hippocampal homogenate. KA treatment resulted in decreased Mn-superoxide dismutase expression and diminished the mitochondrial membrane potential. Furthermore, KA treatment increased intramitochondrial Ca(2+) and promoted ultrastructural degeneration in hippocampal mitochondria. Treatment with ginsenosides dose-dependently attenuated convulsive behavior and the KA-induced mitochondrial effects. Protection appeared to be more evident in mitochondria than in tissue homogenates. Collectively, the results suggest that ginsenosides prevent KA-induced neurotoxicity by attenuating mitochondrial oxidative stress and mitochondrial dysfunction.     

Stagewise separation to improve continuous centrifugal blood cell separators

Staging is a technique used to improve blood cell collection efficiencies. In this paper, fractional cell recoveries are presented as functions of hematocrit as well as flow distribution. Material balances are presented, and the effect of increasing the number of stages studied in relation to increases in white blood cell collection efficiencies.     

Synthesis and Solubility of Collagen in Rats during Recovery after High-dose Cyclophosphamide Administration

Abstract: The metabolism of collagen and mineral was studied during a nine-day postmedicational period in young, male rats receiving high-dose intraperitoneal cyclophosphamide treatment every second day for 12 days. Two days after ending medication the white blood cell counts (WBC) were reduced by about 70%. Both synthesis and solubility of collagen were suppressed by the present medication 2 days after termination of treatment. This suppression continued throughout the 9-day postmedicational period in bones, whereas in connective tissue of porous, ceramic implants both total collagen and the amount of salt soluble collagen regained normal values 9 days after cessation of treatment. Increased mineralization was found 2 days after ending medication and this high degree of mineralization persisted during the postmedicational period studied. Serum albumin levels were reduced and no increases were detected during the postmedicational period. The suggestion is made that the general protein synthesis is affected by high-dose cyclophosphamide administration.     

Registration of localization, occlusion and occluding materials for failing screw joints in the Brånemark implant system

This study is based on data from routine follow‐up registration following functional loading of a consecutive number of osseointegrated prostheses at the Dental School, University of Oslo. Fifty‐six patients with 240 Brånemark implants were examined 24 months after the implants were loaded, and a protocol form for collecting information about the status of the treatment was completed. The examinations included registration of oral hygiene, pathological alterations in soft and hard tissues, type of material used in contacting occlusal surfaces, occlusal design and technical and mechanical failures. All superstructures, except CeraOne single‐tooth prostheses. were unscrewed for inspection of implant and screw joint mobility. Eighty‐three per cent of the implants were found in the upper and lower frontal segments of the jaws. The survival rate for individual implants in this study was 94%. which is well within the generally accepted level for osseointegrated implant systems. Plaque and soft tissue complications were low and could not be associated with the early losses of implants. Group function was the preferred design of the occlusal contact pattern (53.4%), followed by 37% for canine guidance and about 9% for balanced articulation. Fourteen abutment screws and 7 gold screws loosened during the period between permanent loading and the first follow‐up registration. A majority of the failures occurred in osseointegrated bridges occluding with complete dentures in the opposite jaw. The failing screw joints were found in 25% of the patients, which means that one fourth of the patients needed extra mending appointments. The failures are assumed to be iatrogenic, and measures to avoid them are discussed.     

Effects of Cyclophosphamide on the Formation and Solubility of Collagen

Abstract: The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesis.     

Quercetin attenuates oxygen-glucose deprivation- and excitotoxin-induced neurotoxicity in primary cortical cell cultures

The possible role of quercetin, a naturally occurring plant flavonoid, in protecting against oxygen-glucose deprivation (OGD)-, excitotoxins-, and free radical-induced neuronal injury in mouse cortical cell cultures was investigated. Pre- and co-treatment with quercetin (100 microM) inhibited 50 min OGD-, 20 microM N-methyl-D-aspartate (NMDA)-, and 50 microM kainate-induced neurotoxicity by 36, 22, and 61%, respectively. Quercetin significantly ameliorated free radical-induced neuronal injury caused by buthionine sulfoximine, sodium nitroprusside, ZnCl(2), and FeCl(2). These results suggest that quercetin may contribute a neuroprotective action against ischemic neural injury, partially via antioxidant actions.     

Phentolamine inhibits the pacemaker activity of mouse interstitial cells of Cajal by activating ATP-sensitive K<Superscript>+</Superscript> channels

The aim of this study was to clarify if phentolamine has proven effects on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine involving the ATPsensitive K⁺ channels and adrenergic receptor. The actions of phentolamine on pacemaker activities were investigated using whole-cell patch-clamp technique and intracellular Ca²⁺ analysis at 30°C in cultured mouse intestinal ICC. ICC generated spontaneous pacemaker currents at a holding potential of −70 mV. Treatment with phentolamine reduced the frequency and amplitude of the pacemaker currents and increased the resting outward currents. Moreover, under current clamping (I = 0), phentolamine hyperpolarized the ICC membrane and decreased the amplitude of the pacemaker potentials. We also observed that phentolamine inhibited spontaneous [Ca²⁺]_i oscillations in ICC. The alpha-adrenergic drugs prazosin, yohimbine, methoxamine, and clonidine had no effect on ICC intestinal pacemaker activity and did not block phentolamine-induced effects. Phentolamine-induced effects on the pacemaker currents and the pacemaker potentials were significantly inhibited by ATP sensitive K⁺ channel blocker glibenclamide, but not by TEA, apamin, or 4-aminopyridine. In addition, the NO synthase inhibitor, L-NAME and the guanylate cyclase inhibitor, ODQ were incapable of blocking the phentolamine-induced effects. These results demonstrate that phentolamine regulates the pacemaker activity of ICC via ATP-sensitive K⁺ channel activation. Phentolamine could act through an adrenergic receptor- and also through NO-independent mechanism that involves intracellular Ca²⁺ signaling.     

Amelioration of experimental autoimmune encephalomyelitis in Lewis rats treated with fucoidan

We examined whether fucoidan affected the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in rats. EAE was induced in Lewis rats that were immunized with guinea‐pig myelin basic protein (MBP) and complete Freund's adjuvant. Fucoidan (50 mg/kg, daily) was administered to rats with EAE intraperitoneally, either in the EAE induction phase from either 1 day before immunization to day 7 post‐immunization (PI), or the effector phase from day 8 to 14 PI, to test which phase of rat EAE is affected by fucoidan treatment. The onset, severity and duration of EAE paralysis in the fucoidan‐treated group in the days 8–14 PI‐treated rats, but not in days ?1–7 PI‐treated rats, were significantly delayed, suppressed and reduced, respectively, compared with the vehicle‐treated controls. Treatment with fucoidan reduced the encephalitogenic response and TNF‐α production during EAE. Moreover, the clinical amelioration coincided with decreased infiltration of inflammatory cells in the EAE‐affected spinal cord. The ameliorative effect of fucoidan on clinical paralysis in EAE‐affected rats may be mediated, in part, by the suppression of the autoreactive T cell response and inflammatory cytokine production. Copyright © 2009 John Wiley & Sons, Ltd.     

Immunogenicity and safety of trivalent inactivated influenza vaccine: a randomized, double-blind, multi-center, phase 3 clinical trial in a vaccine-limited country

Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic.