Panax quinquefolium saponins protects low density lipoproteins from oxidation

Oxidized low-density lipoprotein (Ox-LDL) is believed to be involved in the pathogenesis of atherosclerosis. Panax quinquefolium saponins (PQS) are extracted from the stems and leaves of the North American form of ginseng, Panax quinquefolium. Earlier studies have suggested that this extract improves the lipid profile of hyperlipidemic rats and has antioxidant properties in cultured rat cardiac myocytes. The aims of the present study were to investigate the potential of PQS in reducing LDL oxidation as well as limiting the ability of Ox-LDL to impair endothelium-dependent relaxation in rat aortic rings. LDL was isolated from the plasma of healthy human donors by sequential ultracentrifugation. Native LDL (0.2 or 0.3 mg/ml) was incubated with PQS (0.25-1 mg/ml) for 30 min at 20 degrees C. For comparison, vitamin C (50 microM) was added in place of PQS. Oxidative modification was initiated with 5 microM CuSO4 at 37 degrees C for 0-24 h. In our hands, PQS concentration-dependently reduced lipid peroxide levels as measured by the amount of thiobarbituric acid reactive substances formed. This range of PQS also retarded the alterations in relative electrophoretic mobility of Ox-LDL in a similar manner. Furthermore, measurement of phospholipid fractions content indicated that PQS could reduce the conversion of phosphatidylcholine to lysophosphatidylcholine in Ox-LDL. Functional studies demonstrated that PQS-pretreated Ox-LDL was less potent than untreated Ox-LDL at impairing endothelium-dependent relaxation in rat aortic rings. In conclusion, our results suggest that PQS has antioxidant properties and that reduction of LDL oxidation by PQS may provide a protective effect against the detrimental actions of Ox-LDL.     

Extending the reach of the heterodigital arterialized flap by vein division and repair

The heterodigital arterialized flap is ideal for nonsensory reconstruction of sizable soft-tissue defects in the proximal fingers, web spaces, and the hand. The inclusion of a dorsal vein augments the venous drainage of this digital island flap and avoids the problem of postoperative venous congestion, which is a common problem in digital island flaps. However, the presence of a dorsal vein pedicle inhibits flap mobility somewhat, and the reach of the flap is mainly limited to adjacent fingers. In situations that demand a transfer from a nonadjacent donor finger or when the reach from the adjacent donor finger is inadequate, the dorsal vein pedicle can be temporarily divided and then anastomosed microsurgically after flap transfer is performed. This enables the reach of the flap to be extended up to two fingers from the donor finger. The authors performed this "partially free" heterodigital arterialized flap in 11 consecutive patients between 1991 and 2001. The average size of the defects was 4.4 x 2.3 cm. All of the flaps survived completely, without any evidence of postoperative flap congestion. Healing of all of the flaps was primary and did not result in any scarring. All of the donor fingers had "normal" two-point discrimination of 3 to 5 mm. All of the donor fingers retained excellent or good total active motion, as graded by the criteria of Strickland and Glogovac.     

Ku86 variant expression and function in multiple myeloma cells is associated with increased sensitivity to DNA damage

Ku is a heterodimer of Ku70 and Ku86 that binds to double-stranded DNA breaks (DSBs), activates the catalytic subunit (DNA-PKcs) when DNA is bound, and is essential in DSB repair and V(D)J recombination. Given that abnormalities in Ig gene rearrangement and DNA damage repair are hallmarks of multiple myeloma (MM) cells, we have characterized Ku expression and function in human MM cells. Tumor cells (CD38(+)CD45RA(-)) from 12 of 14 (86%) patients preferentially express a 69-kDa variant of Ku86 (Ku86v). Immunoblotting of whole cell extracts (WCE) from MM patients shows reactivity with Abs targeting Ku86 N terminus (S10B1) but no reactivity with Abs targeting Ku86 C terminus (111), suggesting that Ku86v has a truncated C terminus. EMSA confirmed a truncated C terminus in Ku86v and further demonstrated that Ku86v in MM cells had decreased Ku-DNA end binding activity. Ku86 forms complexes with DNA-PKcs and activates kinase activity, but Ku86v neither binds DNA-PKcs nor activates kinase activity. Furthermore, MM cells with Ku86v have increased sensitivity to irradiation, mitomycin C, and bleomycin compared with patient MM cells or normal bone marrow donor cells with Ku86. Therefore, this study suggests that Ku86v in MM cells may account for decreased DNA repair and increased sensitivity to radiation and chemotherapeutic agents, whereas Ku86 in MM cells confers resistance to DNA damaging agents. Coupled with a recent report that Ku86 activity correlates with resistance to radiation and chemotherapy, these results have implications for the potential role of Ku86 as a novel therapeutic target.     

Giardia lamblia rearranges F-actin and alpha-actinin in human colonic and duodenal monolayers and reduces transepithelial electrical resistance

The mechanisms of epithelial injury in giardiasis remain unknown. The effects of live Giardia lamblia on cellular G-actin, F-actin, alpha-actinin, and electrical resistance of human intestinal epithelial monolayers were investigated using SCBN and Caco2 cell lines grown on chamber slides or Transwell filter membranes. In separate experiments, some monolayers were also exposed to sonicated trophozoites, some to supernatant from live G. lamblia cultures, and some with or without the Ca2+ channel blocker verapamil. After 2, 24, or 48 hr of coincubation with G. lamblia, monolayers were assessed for cytoskeletal arrangement under fluorescence and confocal laser microscopy, and transepithelial electrical resistance was measured. Exposure to live G. lamblia trophozoites induced localized condensation of F-actin and loss of perijunctional alpha-actinin while G-actin remained unchanged. Confocal laser microscopy indicated that F-actin rearrangement was not affected by verapamil and was localized within the terminal web area. Coincubation of monolayers with G. lamblia lysates or with spent medium alone similarly rearranged F-actin. Verapamil alone did not alter F-actin. Electrical resistance of SCBN and Caco2 monolayers exposed to G. lamblia was significantly decreased versus controls regardless of whether live or lysed trophozoite samples were used. The results indicate that G. lamblia-induced epithelial injury is associated with F-actin and alpha-actinin rearrangements in the terminal web area via mechanisms independent of extracellular Ca2+. These alterations are associated with reduced transepithelial electrical resistance and are due at least in part to trophozoite products.     

Permeability study of vertebral cancellous bone using micro-computational fluid dynamics

Understanding of cancellous bone permeability is lacking despite its importance in designing tissue engineering scaffolds for bone regeneration and orthopaedic surgery that relies on infiltration of bone cement into porous cancellous bone. We employed micro-computational fluid dynamics to investigate permeability for 37 cancellous bone specimens, eliminating stringent technical requirements of bench-top testing. Microarchitectural parameters were also determined for the specimens and correlated, using uni-variate and multi-variate regression analyses, against permeability. We determined that bone surface density, trabecular pattern factor, structure model index and trabecular number are other possible predictors of permeability (with R values of 0.47, 0.44, 0.40 and 0.33), in addition to the commonly used porosity parameter (R value of 0.38). Pooling these parameters and performing multi-variate linear regression analysis improved yield the R-value of 0.50, indicating that porosity alone is a poor predictor of cancellous bone permeability and, therefore, other parameters should be included for a better and improved linear model.     

Overexpression of Df4CL1 from Dryopteris fragrans Enhances Flavonoids and Lignin Production in Transgenic Tobacco

Russian Journal of Plant Physiology - Dryopteris fragrans (L.) Schott is a fern in the family Dryopteridaceae that shows a good curative efficacy against several skin diseases, such as psoriasis...     

Does structural change in the zooplankton community affect larval fish feeding in anthropogenically disturbed tropical waters?

Environmental Biology of Fishes - Anthropogenic perturbations and climate change have altered the zooplankton community structure in the Klang Strait during the past 30 years, in that the...     

Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality

Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.