Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Embolization of percutaneous transhepatic portal venous access tract with N-butyl cyanoacrylate.

OBJECTIVE: To evaluate the safety and feasibility of N-butyl cyanoacrylate (N-BCA) embolization of percutaneous transhepatic portal venous access tract and to establish an appropriate technique. METHODS: 40 consecutive patients underwent percutaneous transhepatic portal venous intervention for various reasons. Embolization of percutaneous transhepatic portal venous access tract was performed after the procedure in all of the patients using N-BCA and Lipiodol® (Lipiodol Ultra Fluide; Laboratoire Guerbet, Aulnay-sous-Bois, France) mixture. Immediate ultrasonography and fluoroscopy were performed to evaluate perihepatic haematoma formation and unintended embolization of more than one segmental portal vein. Follow-up CT was performed, and haemoglobin and haematocrit levels were checked to evaluate the presence of bleeding. RESULTS: Immediate haemostasis was achieved in all of the patients, without development of perihepatic haematoma or unintended embolization of more than one segmental portal vein. Complete embolization of percutaneous access tract was confirmed in 39 out of 40 patients by CT. Seven patients showed decreased haemoglobin and haematocrit levels. Other complications included mild pain at the site of embolization and mild fever, which resolved after conservative management. 16 patients died during the follow-up period owing to progression of the underlying disease. CONCLUSION: Embolization of percutaneous transhepatic portal vein access tract with N-BCA is feasible and technically safe. With the appropriate technique, N-BCA can be safely used as an alternate embolic material since it is easy to use and inexpensive compared with other embolic materials. ADVANCES IN KNOWLEDGE: This is the first study to investigate the efficacy of N-BCA for percutaneous transhepatic portal venous access tract embolization.

Lactoferrin from bovine colostrum regulates prolyl hydroxylase 2 activity and prevents prion protein-mediated neuronal cell damage via cellular prion protein.

Prion disorders are associated with the conversion of normal cellular prion protein (PrPc) to the abnormal scrapie isoform of prion protein (PrPsc). Recent studies have shown that expression of normal PrPc is regulated by hypoxia-inducible factor-1 alpha (HIF-1α), and that lactoferrin increases full-length PrPc on the cell surface. Lactoferrin is an 80-kDa iron-binding glycoprotein with various biological activities, including iron-chelating ability. HIF-1α and the associated ubiquitin-proteasome pathway are regulated by HIF prolyl-hydroxylases 2 (PHD2). We hypothesized that lactoferrin regulates PHD2 expression and enzymatic activity, and the PHD2 regulation promotes HIF-1α stability and prevention of neuronal cell death mediated by prion protein (PrP) residues (106-126). Lactoferrin prevented PrP (106-126)-induced neurotoxicity by the induction of PrPc expression via promoting HIF-1α stability in neuronal cells. Our results demonstrated that lactoferrin prevented PrP (106-126)-induced neurotoxicity via the up-regulation of HIF-1α stability determined by PHD2 expression and enzymatic activity. These findings suggest that possible therapies such as PHD2 inhibition, or promotion of lactoferrin secretion, may have clinical benefits in neurodegenerative diseases, including prion disease.

The clinical and histological effect of home-use, combination blue-red LED phototherapy for mild-to-moderate acne vulgaris in Korean patients: a double-blind, randomized controlled trial.

BACKGROUND: Blue and red light have been reported to have beneficial effects on acne. However, there has been no double-blind, randomized study of acne treatment for combined blue and red light-emitting diode (LED) devices, and the associated molecular mechanisms have rarely been investigated. OBJECTIVES: To evaluate the efficacy, safety and histological changes of combined blue and red LED phototherapy for acne vulgaris. METHODS: Thirty-five patients with mild-to-moderate acne were randomly assigned to either a home-use irradiation group using an LED device, or a control group using a sham device. The treatment group was instructed to serially irradiate their forehead and cheeks with 420-nm blue light and 660-nm red light for 2.5 min twice daily for 4 weeks. RESULTS: At the final visit at 12 weeks, both inflammatory and noninflammatory acne lesions had decreased significantly, by 77% and 54%, respectively, in the treatment group. No significant difference was observed in the control group. In the treatment group, sebum output reduction, attenuated inflammatory cell infiltrations and a decreased size of the sebaceous gland were found. The immunostaining intensities for interleukin (IL)-8, IL-1α, matrix metalloproteinase-9, toll-like receptor-2, nuclear factor-κB, insulin-like growth factor-1 receptor and sterol response element binding protein (SREBP)-1 were reduced concomitantly. Messenger RNA expression of SREBP-1c was also decreased. No severe adverse reactions were reported. CONCLUSIONS: This LED phototherapy was safe and effective for treating not only inflammatory but also noninflammatory acne lesions, with good compliance. The experimental results correlated well with clinical results, partly elucidating the related molecular mechanisms.

Anti-influenza virus activity of green tea by-products in vitro and efficacy against influenza virus infection in chickens.

Polyphenolic compounds present in green tea, particularly catechins, are known to have strong anti-influenza activity. The goal of this study was to determine whether green tea by-products could function as an alternative to common antivirals in animals compared to original green tea. Inhibition of viral cytopathic effects ascertained by neutral red dye uptake was examined with 50% effective (virus-inhibitory) concentrations (EC50)determined. Against the H1N1 virus A/NWS/33, we found the anti-influenza activity of green tea by-products (EC50 = 6.36 µg/mL) to be equivalent to that of original green tea (EC50= 6.72 µg/mL). The anti-influenza activity of green tea by-products was further examined in mouse and chicken influenza infection models. In mice, oral administration of green tea by-products reduced viral titers in the lungs in the early phase of infection, but they could not protect these animals from disease and death. In contrast, therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001). We also demonstrated that unidentified hexane-soluble fractions of green tea by-products possessed strong anti-influenza activity, in addition to ethyl acetate-soluble fractions, including catechins. This study revealed green tea by-product extracts to be a promising novel antiviral resource for animals.

Inactivated H9N2 avian influenza virus vaccine with gel-primed and mineral oil-boosted regimen could produce improved immune response in broiler breeders.

The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.

Anti-oxidative and anti-inflammatory activities of placental extracts in benzo[a]pyrene-exposed rats.

OBJECTIVE: Placental extracts (PE) have been used for years as a folk remedy in Asian countries. PE mediates alleviation of menopausal symptoms, wound healing, liver regeneration and anti-inflammatory responses. In this study, we evaluated the protective effects of PE on rats exposed to benzo[a]pyrene (BaP). METHODS: The composition of amino acids, sugars and fatty acids in PE was analyzed. The effect of PE on DNA damage was determined by Comet assay, and oxidative damage was determined by measuring the activity of superoxide dismutase and the levels of lipid peroxidation. The effect of PE on cytokines and immunoglobulin levels was determined by western blot analysis. RESULTS: Exposure of rats to BaP significantly increased the Olive Tailmoments compared to controls, while pre-treatment with PE composed of diverse amino acids, monosaccharides and fatty acids significantly decreased the Olive Tailmoments induced by BaP. In addition, oxidative stress induced by BaP was attenuated by pre-treatment with PE. Furthermore, PE pre-treatment significantly decreased the levels of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. CONCLUSION: Pre-treatment of rats with PE significantly attenuates oxidative damage and immunotoxicity induced by BaP. These findings suggest the further studies regarding the protective effects of PE against environmental toxicants in humans.

The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest.

Berberine is a pure phenanthren alkaloid isolated from the roots and bark of herbal plants such as Berberis, Hydrastis canadensis and Coptis chinensis. Berberine has been established to inhibit the growth of breast cancer cells, but its effects on the drug resistance and anoikis-resistance of breast cancer cells have yet to be elucidated. Anoikis, or detachment-induced apoptosis, may prevent cancer progression and metastasis by blocking signals necessary for survival of localized cancer cells. Resistance to anoikis is regarded as a prerequisite for metastasis; however, little is known about the role of berberine in anoikis-resistance. We established anoikis-resistant cells from the breast cancer cell lines MCF-7 and MDA-MB-231 by culturing them on a Poly-Hema substratum. We then investigated the effects of berberine on the growth of these cells. The anoikis-resistant cells had a reduced growth rate and were more invasive than their respective adherent cell lines. The effect of berberine on growth was compared to that of doxorubicine, which is a drug commonly used to treat breast cancer, in both the adherent and anoikis-resistant cell lines. Berberine promoted the growth inhibition of anoikis-resistant cells to a greater extent than doxorubicine treatment. Treatment with berberine-induced cell cycle arrest at G0/G1 in the anoikis-resistant MCF-7 and MDA-MB-231 cells as compared to untreated control cells. In summary, these results revealed that berberine can efficiently inhibit growth by inducing cell cycle arrest in anoikis-resistant MCF-7 and MDA-MB-231 cells. Further analysis of these phenotypes is essential for understanding the effect of berberine on anoikis-resistant breast cancer cells, which would be relevant for the therapeutic targeting of breast cancer metastasis.

Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort.

BACKGROUND: Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. METHODS: This case-control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status. RESULTS: The median excretion of daidzein was 0.173 nmol mg(-1) creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31-0.98, P(trend)=0.03) and seemed to apply to localized (P(trend)=0.08) as well as advanced or high-grade cancer (P(trend)=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk. CONCLUSION: Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.

Physicochemical properties, and antioxidant and antimicrobial effects of garlic and onion powder in fresh pork belly and loin during refrigerated storage.

Pork loin and belly cuts were pumped to 110% of their original weight with solutions containing 5% of various ingredients (sodium ascorbate, garlic, and onion powder), and evaluated the physicochemical properties, and antioxidant and antimicrobial activities during refrigerated storage at 8 degrees C. The addition of garlic and onion powder tended to increase redness (a) and yellowness (b) in both the belly lean and loin with the exception of a few cases. Free fatty acid values in both pork belly and loin cuts were reduced with the addition of these ingredients, as compared to the control. Significant differences in peroxide values were observed in sodium ascorbate and garlic-injected belly, and in sodium ascorbate and onion-injected loin, as compared to the control. Thiobarbituric acid reactive substance values in the pork belly with garlic or onion powder were significantly lower than in the belly without these ingredients or with sodium ascorbate (P < 0.05). Total plate counts were lower in both the belly and loin containing garlic and onion powder, as compared to the control. In both the belly and loin cuts, the content of oxidative products (volatile compounds) was reduced with the addition of garlic and onion powder, particularly the aldehydes (hexanal). Overall, garlic and onion in enhanced meats showed an antioxidant activity as effective as that of sodium ascorbate and also an antimicrobial effect to inhibit the growth of total bacteria and Enterobacteriaceae.

Environmental risk assessment of genetically engineered herbicide-tolerant Zoysia japonica.

Herbicide-tolerant Zoysia grass (Zoysia japonica Steud.) has been generated previously through Agrobacterium tumefaciens-mediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1.2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.

The effects of apigenin-7-O-beta-D-glucuronopyranoside on reflux oesophagitis and gastritis in rats.

1. This study evaluated the inhibitory action of apigenin-7-O-beta-D-glucuronopyranoside (AGC), apigenin, and omeprazole on reflux oesophagitis and gastritis in rats. AGC was isolated from Clerodendron trichotomum leaves. 2. Oesophagitis and gastritis were induced by surgical procedure and the administration of indomethacin, respectively. The intraduodenal (i.d.) administration of AGC decreased the volume of gastric juice and increased the gastric pH compared with apigenin and omeprazole. The acid output was more inhibited by AGC in a dose-dependent manner than by apigenin and omeprazole. Compared with apigenin and omeprazole, AGC significantly decreased the size of gastric lesions, which were induced by exposure of the gastric mucosa to indomethacin. 3. Malondialdehyde (MDA) content, which is the end product of lipid peroxidation, was increased significantly after the induction of reflux oesophagitis. The MDA content was decreased by AGC (i.d. 3 mg kg(-1)), but not by either apigenin or omeprazole. This suggests that AGC has an antioxidative effect. In the oesophagitis group, the mucosal levels of glutathione (GSH) were significantly lower than that in the normal group. However, the GSH levels were preserved after administering the AGC, suggesting that AGC possesses scavenging activity. 4. In summary, AGC is more potent than apigenin and omeprazole at inhibiting reflux oesophagitis and gastritis and may therefore be a promising drug for their treatment.

Review on the role of dietary zinc in poultry nutrition, immunity, and reproduction.

Zinc is an important nutrient in animal metabolism. In poultry, zinc serves not only as a nutrient but can also be used as a dietary supplement to manipulate the reproductive system of the bird. This article summarizes the general biochemistry, physiology, and nutritional aspects of zinc metabolism to provide a brief overview on what is known regarding zinc. The potential role of zinc in poultry immune response, Salmonella infection, and molting are emphasized.

Using a feed-grade zinc propionate to achieve molt induction in laying hens and retain postmolt egg production and quality.

A commercial-feed-grade form of zinc propionate was examined as a potential feed amendment at a concentration of 1% zinc to induce molt in 90-wk-old hens. Dietary treatments consisted of 4 treatment groups of 28 birds each randomly assigned to either (1) molted conventionally by feed withdrawal, (2) 1% zinc as Zn acetate, (3) 1% zinc as Zn propionate, or (4) nonmolted control for 9 d. Ovary weights of hens fed Zn acetate or Zn propionate were not significantly different from each other, but hens fed Zn acetate or Zn propionate were significantly (p<0.05) lighter than the ovary weight of nonmolted control hens. Zinc concentrations in the kidney and liver were significantly (p<0.05) increased in both Zn acetate- and Zn propionate-molted hens when compared to either nonmolted control-fed hens or feed-withdrawal molted hens. Over the entire 3-mo postmolt period, there were no significant differences in interior or exterior egg qualities among the four treatments. Egg production of hens fed Zn acetate was significantly lower than feed-withdrawal hens, Zn propionate-fed hens, or nonmolted control hens (p<0.05). The data of the current study demonstrated that feeding a feed grade of Zn propionate (1% Zn)-supplemented diet can induce molt and retain postmolt egg quality and production comparable to hens molted by feed withdrawal.

Mesenchymal progenitor cells in the human umbilical cord.

Mesenchymal progenitor or stem cells (MPCs) isolated from fetal blood, liver, and bone marrow are a population of multipotential cells that can proliferate and differentiate into multiple mesodermal tissues including bone, cartilage, muscle, ligament, tendon, fat, and stroma. The objective of this study was to isolate and characterize MPCs in the human umbilical cord. The suspensions of endothelial and subendothelial cells in cord vein were collected and cultured in M199 supplemented with 10% fetal bovine serum (FBS). Of 50 umbilical cord samples, 3 had numerous fibroblastoid cells morphologically distinguishable from endothelial cells. Fibroblastic cells displayed lack of expression of vWF, Flk-1, and PECAM-1, indicating the endothelial cell-specific marker. To investigate the differentiation potentials, the cells were cultured in adipogenic or osteogenic medium for 2 weeks. Fibroblast-like cells treated with adipogenic supplementation showed Oil red O-positive staining and expressed adipsin, FABP4, LPL, and PPARgamma2 genes by reverse transcriptase polymerase chain reaction (RT-PCR). In osteogenic differentiation, alkaline phosphatase activity and calcium accumulation were detected. RT-PCR studies determined that Cx43, osteopontin, and Runx2 genes were expressed in the osteogenic cultures. Among three cell lines cultured continuously for passage 10, two had normal karyotypes; however, one retained a karyotype of mos 46,XY[19]/47,XY,+mar[3]. These observations suggest that MPCs are present in human umbilical cord and possess several typical traits of MPCs.

Effects of high zinc diets using zinc propionate on molt induction, organs, and postmolt egg production and quality in laying hens.

This study was conducted to determine the ability of an alternative salt form of 1% Zn, Zn propionate, to induce molt in 66-wk-old hens. The hens were randomly assigned to 4 treatment groups of 27 or 28 birds each: a) molted conventionally by feed withdrawal, b) 1% Zn as Zn acetate, c) 1% Zn as Zn propionate, or d) nonmolted control for 9 d. Feed intake was (P < 0.05) depressed in Zn acetate and Zn propionate hens when compared with nonmolted control hens during the 9 d. Ovary weights of hens undergoing feed withdrawal, Zn acetate, or Zn propionate were not (P > 0.05) different from each other, but all were (P < 0.05) lighter than the ovary weights of nonmolted control hens. Zinc concentrations in the kidney and liver were (P < 0.05) increased in Zn acetate and Zn propionate molted hens when compared with nonmolted hens on the control diet or hens molted by feed withdrawal. Bone ash values were (P < 0.05) increased for Zn acetate and Zn propionate molted hens or nonmolted control hens as compared with molted hens on feed withdrawal. Over the entire 3-mo postmolt period, there were no significant differences in interior egg qualities, but egg weights from hens fed Zn propionate were (P < 0.05) heavier than those from hens on feed withdrawal. The data of the current study demonstrated that feeding a Zn propionate (1% zinc)-supplemented diet can induce molt.

Molecular cloning of a cytosolic ascorbate peroxidase cDNA from cell cultures of sweet potato and its expression in response to stress.

A cDNA encoding a cytosolic ascorbate peroxidase (APX), swAPX1, was isolated from cell cultures of sweet potato ( Ipomoea batatas) by cDNA library screening, and its expression in the context of various environmental stresses was investigated. swAPX1 contains an ORF of 250 amino acids (27.5 kDa) encoding a protein with a pI value of 5.32. The swAPX1 ORF does not code for a transit peptide, suggesting that the product is a cytosolic isoform. RNA blot analysis showed that swAPX1 gene is expressed in cultured cells and mature leaves, but not in stems, non-storage or storage roots of sweet potato. The level of swAPX1 RNA progressively increased during cell growth in suspension cultures. In leaf tissues, the gene responded differentially to various abiotic stresses, as revealed by RT-PCR analysis. swAPX1 was highly induced in leaves by wounding, and treatment with methyl viologen (50 microM), hydrogen peroxide (440 mM), abscisic acid (ABA; 100 microM) or exposure to high temperature (37 degrees C). In addition, the gene was strongly induced in the leaves following inoculation with a bacterial pathogen ( Pectobacterium chrysanthemi). These results indicate that swAPX1 may be involved in hydrogen peroxide-detoxification and thus help to overcome the oxidative stress induced by abiotic and biotic stresses.

Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats.

Externally visible growth of the body is the result of proliferation of chondrocytes and longitudinal bone growth. The effects of the Korean herbal medicine, Jaoga-Yukmiwon((R)), on the growth of adolescent rats were investigated in the present study. The proliferation ratio of chondrocytes was calculated from 5-bromo-2'-deoxyuridine incorporation during DNA synthesis. The 5-bromo-2'-deoxyuridine incorporation ratio of the control group was 21.1 +/- 3.5%, and Jaoga-Yukmiwon((R)) administration markedly increased the ratio to 34.5 +/- 4.6% (p < 0.05). The bone formation rate of longitudinal bone was estimated by labelling with tetracycline, which binds to newly formed bone. The bone formation rate in the tibia of Jaoga-Yukmiwon((R))-administered rats was increased to 405.1 +/- 4.3 micro m (p < 0.05) from 292.2 +/- 11.8 micrometer (control value). The height of the growth plate in the administrated rats was increased to 614.6 +/- 10.0 micro m (p < 0.05) from 552.3 +/- 17.1 micro m. The bone morphogenetic protein-2 immunostaining in the growth plate was also increased. These results suggest that Jaoga-Yukmiwon((R)) may promote longitudinal bone growth during the developmental period.

RAFTK/Pyk2 involvement in platelet activation is mediated by phosphoinositide 3-kinase.

Platelet activation by different agonists initiates a signalling cascade involving the phosphorylation of several protein kinases, which control key regulatory events. Previously, we demonstrated that the related adhesion focal tyrosine kinase (RAFTK, Pyk2) was involved in an early phase of platelet activation, independent of integrin and glycoprotein IIb-IIIa activation. In this study, we demonstrate that RAFTK is co-immunoprecipitated with phosphoinositide 3-kinase (PI3K) upon platelet activation, and that thrombin, ADP and collagen induced the phosphorylation of both PI3K and RAFTK. A low dose of thrombin (0.015 U/ml) induced RAFTK phosphorylation and platelet aggregation in a PI3K activity-dependent manner, whereas a high dose of thrombin (0.1 U/ml) induced these events in a PI3K activity-independent manner. ADP and collagen also induced RAFTK phosphorylation and platelet aggregation in a PI3K activity-dependent manner, similar to that of the low-dose thrombin. Furthermore, protein tyrosine phosphatase activity was associated with RAFTK in response to platelet activation, and was found to be that of protein tyrosine phosphatase-2 (SHP-2). The association of SHP-2 with RAFTK was PI3K-dependent and was increased upon RAFTK phosphorylation. Taken together, our results strongly suggest that the involvement of RAFTK in platelet activation is mediated via the PI3K pathway.