Inhibitory effects of ginseng total saponins on hypoxia-induced dysfunction and injuries of cultured astrocytes

The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% N(2)/5% CO(2) for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by [(3)H]O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxiain vitro.     

Synthesized TGF-beta s in RPE regulates cellular proliferation

Retinal pigment epithelial (RPE) cells transdifferentiate in culture, a transition which is accompanied by a shift in biological activity. The present study investigates whether transforming growth factor (TGF)-beta has the same effects on morphologically transformed RPE cells that it has on primary RPE cells. It also evaluates the autocrine and paracrine activities of TGF-beta s synthesized by RPE cells as well as the anti-TGF-beta effect of mannose-6-phosphate (M-6-P). RPE cells were subcultured at the sixth passage to induce morphological change. The effect of second passaged RPE-conditioned medium (CM) on DNA synthesis was evaluated by the incorporation of 3H-thymidine in rabbit subconjunctival fibroblasts (SCFs) and primary RPE cells. The presence of TGF-beta in RPE-CM was determined using immunoblotting analysis. And the inhibitory effect of M-6-P on cell proliferation mediated by RPE-CM was also analyzed using 3H-thymidine incorporation into DNA. TGF-beta 1, TGF-beta 2, and TGF-beta 3 inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, but the spindle-shaped sixth passaged RPE cells were not inhibited by these growth factors. The medium conditioned by RPE cells stimulated the proliferation of SCFs and inhibited the proliferation of primary RPE cells, in a manner similar to TGF-beta. When this medium was precipitated with either anti-TGF-beta 1, anti-TGF-beta 2, or anti-TGF-beta 3 antibodies, all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected. Mannose-6-phosphate significantly blocked the effect of RPE-CM on cell proliferation. These findings indicate that RPE cells produce biologically functional TGF-beta s and that M-6-P can block the inhibitory effect of RPE-CM on cell proliferation.     

Bioisosterism: Interchange of 4-OH to 4-NH2 in vanillin or homovanillin ring of capsaicinoids

A series of 4-amino Capsaicin analogs 15, 17 and 19 were prepared to investigate the bioisosteric effect of 4-amino group, and all these compounds exhibited moderate or weak potency from their analgesic test. From our previous results and others, 4-hydroxyl group as well as 3-methoxy substituent could be crucial for high analgesic activity. This biological result also shows that the activity is sensitive to alkyl chain length in hydrophobic region and the phenylacetic amides 19 are more active than the corresponding urea derivatives 17.     

Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on immobilization stress-induced antinociception in the mouse.

The effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) 3-isobutyl-1-methylxanthine (IBMX), cholera toxin (CTX) and pertussis toxin (PTX) administration on immobilization-induced antinociception were studied in ICR mice. Antinociception was assessed by the tail-flick assay. Immobilization of the mouse increased inhibition of the tail-flick response for at least 1 h. The pretreatment with i.t. IBMX (0.01-1 ng), but not i.c.v. IBMX, significantly attenuated immobilization-induced inhibition of the tail-flick response. The pretreatments with i.c.v. PTX (0.05-0.5 microg) as well as i.t. CTX, but neither i.c.v. CTX (0.05-0.5 microg) nor i.t. PTX, potentiated the inhibition of the tail-flick response induced by immobilization stress. Our results suggest that spinally located phosphodiesterase appears to be involved in the production of immobilization stress-induced antinociception. In addition, inactivation of supraspinally located PTX-sensitive G-proteins and spinally located CTX-sensitive G-proteins may modulate immobilization stress-induced antinociception.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.