Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs.

RATIONALE: Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination. OBJECTIVES: We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR). METHODS: We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats. RESULTS: SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs. CONCLUSIONS: SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

2-Methoxystypandrone represses RANKL-mediated osteoclastogenesis by down-regulating formation of TRAF6-TAK1 signalling complexes.

BACKGROUND AND PURPOSE: 2-Methoxystypandrone (2-MS) is a naphthoquinone isolated from Polygonum cuspidatum, a Chinese herb used to treat bone diseases. Here we have determined whether 2-MS antagonised osteoclast development and bone resorption. EXPERIMENTAL APPROACH: RAW264.7 cells were treated with receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) to induce differentiation into osteoclasts. RT-PCR and Western blot were used to analyse osteoclast-associated gene expression and signalling pathways. KEY RESULTS: The number of multinuclear osteoclasts, actin rings and resorption pit formation were markedly inhibited by 2-MS, targeting osteoclast differentiation at an early stage and without significant cytotoxicity. The anti-resorption effect of 2-MS was accompanied by decreasing dendritic cell-specific transmembrane protein and matrix metalloproteinase-9 (MMP-9) mRNA expression. RANKL-increased MMP-9 gelatinolytic activity was also attenuated by concurrent, but not by subsequent addition of 2-MS. 2-MS markedly inhibited not only the RANKL-triggered nuclear translocations of NF-kappaB, c-Fos and nuclear factor of activated T cells c1 (NFATc1), but also the subsequent NFATc1 induction. Degradation of IkappaB and phosphorylation of mitogen-activated protein kinases were also suppressed. RANKL facilitated the formation of signaling complexes of tumour necrosis factor receptor-associated factor 6 and transforming growth factor beta-activated kinase 1 (TRAF6-TAK1), important for osteoclastogenesis and formation of such signalling complexes was prevented by 2-MS. CONCLUSIONS AND IMPLICATIONS: The anti-osteoclastogenic effects of 2-MS could reflect the block of RANKL-induced association of TRAF6-TAK1 complexes with consequent decrease of IkappaB-mediated NF-kappaB and mitogen-activated protein kinases-mediated c-Fos activation pathways and suppression of NFATc1 and other gene expression, essential for bone resorption.

Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats.

Silymarin, a standardized extract of the milk thistle (Silybum marianum), has a long tradition as a herbal remedy, and was introduced as a hepatoprotective agent a few years ago. However, the therapeutic effects of silymarin remain undefined. Carbon tetrachloride (CCl4) is a xenobiotic used extensively to induce oxidative stress and is one of the most widely used hepatic toxins for experimental induction of liver fibrosis in the laboratory. In this study, we investigated the restoration of the CCl4-induced hepatic fibrosis by high dose of silymarin in rats. After treatment with oil (as normal group; n = 6) or CCl4 [as model (n = 7) and therapeutic (n = 7) groups] by intragastric delivery for 8 weeks for the induction of liver fibrosis, the rats in the normal and model group were administered orally normal saline four times a week for 3 weeks whilst the therapeutic group received silymarin (200 mg/kg). The histopathological changes were observed with Masson staining. The results showed that the restoration of the CCl4-induced damage of liver fibrosis in the therapeutic group was significantly increased as compared to that in the model group. Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue. Therefore, these findings indicated that silymarin may have the potential to increase the resolution of the CCl4-induced liver fibrosis in rats.

Fast repair of the poly G hydroxyl radical adduct by two phenylpropanoid glycosides.

The repair activities and the reaction mechanisms of two phenylpropanoid glycosides (PPGs), isolated from a herb used in Chinese folk medicine, towards the oxidizing hydroxyl radical adduct of poly G were studied with a pulse radiolytic technique. On pulse irradiation of a nitrous oxide saturated 4 mM aqueous solution of poly G containing one of the tested compounds, the transient absorption spectrum of the hydroxyl radical adduct of poly G decays with the formation of that of the phenoxyl radical of the tested compound within several tens microseconds after the electron pulse irradiation. The results indicated that there was a repair reaction between the hydroxyl radical adduct of poly G and the compounds tested. The rate constants for the repair reactions of poly G hydroxyl radical adducts by verbasicoside and cistanoside C were determined to be 1.4 and 1.0 x 10(9) M(-1) x s(-1), respectively.

Microbial response to bensulfuron-methyl treatment in soil.

A laboratory incubation study was conducted to evaluate the effect of bensulfuron-methyl treatment on soil microbial biomass and N-mineralization of a loamy sand soil. The herbicide was applied at 0 (control), 0.01 (field rate), 0.1, and 1.0 microg g(-1), and soil microbial biomass carbon (C(mb)), soil microbial biomass nitrogen (N(mb)), and N-mineralization rate (k) were measured at different times after herbicide treatment. Compared to the untreated soil, C(mb) and N(mb) decreased significantly (p < or = 0.05) within the first 7 days after herbicide treatment at 0.1 and 1.0 microg g(-1), and the impact was greater for N(mb) than for C(mb). Nitrogen mineralization was significantly suppressed during the first 5 days of incubation when the soil was treated with bensulfuron-methyl at 0.1 and 1.0 microg g(-1). The overall impact of bensulfuron-methyl to the soil microbial communities was closely related to the application rate in the range of 0.01-1.0 microg g(-1). This effect, however, was found to be transitory, and significant impact occurred only at high application rates.

Effects of spinach powder fat-soluble extract on proliferation of human gastric adenocarcinoma cells.

Four kinds of assays were used to study the effect of a fat-soluble extract of spinach powder (SPFE) on the proliferation of human gastric adenocarcinoma cell line (SGC-7901) in vitro. These studies included: (i) cell growth assay, (ii) colony forming assay, (iii) MTT colorimetric assay, and (iv) 3H-TdR incorporation assay. The concentrations of SPFE expressed as the level of beta-carotene in the medium were 2 x 10(-8), 2 x 10(-7) and 2 x 10(-6) mol/L beta-carotene in assay (i)-(iii), but 4 x 10(-8), 4 x 10(-7) and 4 x 10(-6) mol/L beta-carotene in assay (iv) respectively. The results indicated that SPFE inhibited the proliferation and colony forming ability of SGC-7901 cells. And in MTT assay, SPFE inhibited the viability of SGC-7901 cells, but no inhibitory effect of SPFE was observed on the viability of lymphocytes in peripheral blood of healthy people. Finally, in the 3H-TdR incorporation test, both SPFE and beta-carotene showed significant inhibitory effects on DNA synthesis in SGC-7901 cells, but SPFE was more effective than beta-carotene.

In vivo and in vitro studies on the antitumor activities of MCP (Malva crispa L. Powder).

Four short-term in vivo and in vitro tests were used to further confirm the antitumor activities of MCP, a vegetable powder, prepared from Malva crispa L. (i) In the H22 hepatoma-transplanting test, MCP had antitumor action, but MCP residue did not show such action; 5-FU appeared to have more potent antitumor activities and more harmful effects than MCP. (ii) In the micronucleus (MN) test, MCP significantly decreased MN frequency. (iii) In the cancer cell culture systems, the MCP fat-soluble extract revealed inhibitory effects on the growth and proliferation of the human hepatoma and the gastric cancer cells in a dose-response manner. (iv) In the colony formation test, MCP also altered the morphology of human gastric cancer cells. It was suggested that MCP could be consumed not only by healthy subjects for cancer prevention but also by patients with cancer as supplementary treatment in combination with anticarcinogenic drug such as 5-FU, cyclophosphamide (CP).

Determination of cinnamic acid and paeoniflorin in traditional Chinese medicinal preparations by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of cinnamic acid in Cinnamomi ramulus and paeoniflorin in Paeoniae radix was established. The samples were separated by a LiChrospher RP-18 column with water-acetonitrile-methanolacetic acid (61:34:5:0.1 or 80:15:5:0.1, v/v) as the mobile phase at a flow-rate of 1.0 ml/min. Cinnamic acid and paeoniflorin were determined by UV detection at 280 and 250 nm, respectively. The method was applied to determine the optimum conditions for the extraction of the traditional Chinese medicinal preparation Huang Chi Chien Chung Tong, which contains Cinnamomi ramulus and Paeoniae radix. The results indicate that the best extraction conditions involved the use of an ultrasonic bath at 60 degrees C for 30 min. In this experiment, butyl paraben and methyl paraben were used as the internal standards for cinnamic acid and paeoniflorin, respectively. A good and reproducible separation of cinnamic acid and paeoniflorin was obtained within 15 min. The method was also applicable to other preparations that contain Cinnamomi ramulus and Paeoniae radix such as Guey Chi Chia Long Ku Muu Li Tong, Kuei Chi Chien Chung Tong and Tang Kuei Chien Chung Tong.

Amnesia following right thalamic haemorrhage.

A 52 year old patient with a right thalamic haemorrhage is described. She suffered from anterograde amnesia and memory impairment for both visual and verbal material. At follow-up after 3 months, despite being fully oriented and having good concentration, her memory impairment was still evident. Reassessment 3 years afterwards showed persistent deficits and no further improvement.

Cerebral haemorrhage in a urban Chinese population.

A prospective study of Chinese patients aged 20-70 years reveals that at least 30.5% of all strokes are due to cerebral haemorrhage. Compared to previous studies in Caucasians, there is both a proportional and absolute increase in cerebral haemorrhage amongst all strokes, alert strokes, or those who presented with just a lacunar syndrome. The cause for this increase is unclear but genetic, dietary, and other environmental factors may be involved.