GD Treatment Research Articles

The influence of La and Gd on prostate cancer DU145 cell-induced osteoblast and osteoclast differentiation

To assess the potential effect of lanthanides(Ln)on the prevention of prostate cancer(PCa)bone metastasis,in this study we report the influence of Ln on PCa cells induced osteoblasts and osteoclasts differentiation.We cultured osteoblast-like MC3T3-e1 cells with conditioned medium(CM)from lanthanum(La)or gadolinium(Gd)treated DU145 cells.MC3T3-e1 differentiation increased in the presence of DU145 CM treated with La,whereas Gd treatment had no effect on MC3T3-e1 differentiation.Using RT-PCR arrays,we observed an increase in the expression of BMP6 genes in DU145 cells treated with La.Western blot analysis demonstrated that LaCl3 treatment increased phosphorylation of c-Jun NH(2)-terminal kinase(JNK).In addition,La reduced the expression of osteoclastogenesis-associated genes RANKL while increasing OPG expression in DU145 cells.Furthermore,La inhibited DU145 cells induced osteoclast formation in an in vitro coculture model of prostate cancer cells with osteoclast precursors generated from mouse bone marrow cells,while Gd failed to show the similar phenomenon in osteoclast differentiation.

Randomized Phase II Trial of Cisplatin, Etoposide, and Radiation Followed by Gemcitabine Alone or by Combined Gemcitabine and Docetaxel in Stage III A/B Unresectable Non-small Cell Lung Cancer

Southwest Oncology Group 9504 demonstrated the feasibility and potential benefit of docetaxel consolidation after etoposide, cisplatin, and radiotherapy in patients with locally advanced non-small cell lung cancer. Our study assessed consolidation with either gemcitabine alone or with docetaxel after identical chemoradiation as used in Southwest Oncology Group 9504. Patients with stage III non-small cell lung cancer and good performance status were included. Treatment consisted of concurrent cisplatin 50 mg/m on days 1 and 8 plus etoposide 50 mg/m on days 1 to 5 for two 28-day cycles plus radiotherapy (62 Gy, 2 Gy daily in 31 fractions over 7 weeks), followed by randomization to either gemcitabine 1000 mg/m on days 1 and 8 (G) or gemcitabine 1000 mg/m on days 1 and 8 plus docetaxel 75 mg/m on day 1 (GD) every 21 days for three cycles. Eighty-three patients were entered, 81 received induction therapy, and 64 were randomized (32 in each arm). Grade 3 or four events, including neutropenia (56.3% vs. 28.1%, p = 0.03), anemia (18.8% vs. 3.1%, p = 0.05), and fatigue (15.6% vs. 6.3%, p = NS), were more frequent with GD compared with G. Among all patients, median survival from registration was 20.8 months (95% confidence interval: 16.4-33.8), and 2-year survival was 46.7% (95% confidence interval: 35.6-57.1). From randomization, median progression-free survival was 5.4 months for G and 13.4 months for GD, and median survival was 16.1 months for G and 29.5 months for GD. Two-year survival rates were 40.6% for G and 55.7% for GD. The doublet, as expected, resulted in more toxicity, particularly myelosuppression and fatigue. Survival associated with the GD treatment arm of this trial exceeds that of previously reported trials.

Yield and soil nutrient balance of a sugarcane plant–ratoon system with conventional and organic nutrient management in sub-tropical India

A 3-year field trial of sugarcane, comprising 11 treatment combinations of different organic manures with and without Gluconacetobacter diazotrophicus (Gd), NPK and an absolute control, on an inceptisol was conducted to assess the effect of these treatments on sugarcane total and economic yield, the benefit:cost ratio, nutrient balance and soil quality in a sugarcane plant–ratoon system. The highest cane yield (78.6 t ha−1) was recorded in the plant crop given vermicompost + Gd, whereas ratoon yields (first and second) were highest (80.8 and 74.9 t/ha−1, respectively) with sulphitation press mud cake (SPMC) + Gd. In both plant and ratoon crops, a number of different organic manures produced the highest cane yield that was also statistically similar to those obtained with using the recommended NPK levels (76.1, 78.2 and 71.7 t/ha for plant crop and subsequent two ratoons, respectively). The highest benefit:cost (B:C) ratio in the plant and two ratoon crops (1.28, 2.36, 2.03 respectively) were obtained with the addition of SPMC + Gd. The nutrient balance for NPK in the soil was highest in the SPMC + Gd treatment. The highest increase in organic C (94%) and total N (87%), in comparison to the initial level, and soil microbial biomass C (113%) and soil microbial biomass N (229%), in comparison to the control treatment, was recorded with the addition of SPMC + Gd. The maximum decrease in soil bulk density (BD) (12%) with an increase in soil aggregate (17%) and water infiltration rate (35%) was obtained with the addition of SPMC. Overall, the sugarcane crop responded well to different organic manures in a multiple ratooning system with a better economic output and improved soil quality. Strategic planning in terms of an integrated application of these manures with inorganic chemicals will not only sustain our soils but will also be beneficial for our farmers in terms of reducing their dependence and expenditure on chemical fertilizers.

Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver

To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.

Photoemission study of (PbEuGd)Te layers under Gd or Te atoms treatment

Substitution of Gd 3+ for Eu 2+ ions in EuTe leads to the introduction of Gd 5d electrons to the conduction band and antiferromagnetic order of EuTe (Heisenberg magnetic semiconductor) can be replaced by ferromagnetic state due to RKKY interaction. The layers were grown by MBE method on BaF 2 (1 1 1) substrate. Layer of Te deposited on top of (EuGd)Te protects surface of oxidation. Heating in 320 °C leads to Te atoms desorption and to improvement of the layer electronic structure. Additional Gd atoms were sequentially deposited on the layer of (PbGd)Te and set of Fano resonance curves were observed for ions of Gd. The Fano type photoemission resonance corresponding to the 4d–4f transitions were studied for Eu and Gd.

Ion-channel Regulation of Chondrocyte Matrix Synthesis in 3D Culture Under Static and Dynamic Compression

Inhibition of various ion channels alters chondrocyte mechanotransduction in monolayer, but the mechanisms involved in chondrocyte mechanotransduction in three- dimensional culture remain unclear. The objective of this study was to investigate the effects of inhibiting putative ion-channel influenced mechanotransduction mechanisms on the chondrocyte responses to static and dynamic compression in three-dimensional culture. Bovine articular cartilage explants were used to investigate the dose-dependent inhibition and recovery of protein and sulfated glycosaminoglycan (sGAG) syntheses by four ion-channel inhibitors: 4-Aminopyridine (4AP), a K(+) channel blocker; Nifedipine (Nf), a Ca(2+) channel blocker; Gadolinium (Gd), a stretch-activated channel blocker; and Thapsigargin (Tg), which releases intracellular Ca(2+) stores by inhibiting ATP-dependent Ca(2+) pumps. Chondrocyte-seeded agarose gels were used to examine the influence of 20 h of static and dynamic loading in the presence of each of the inhibitors. Overall, treatment with the ion-channel inhibitors had a greater effect on sGAG synthesis, with the exception of Nf, which more substantially affected protein synthesis. Treatment with Tg significantly impaired both overall protein and sGAG synthesis, with a drastic reduction in sGAG synthesis. The inhibitors differentially influenced the responses to mechanical stimuli. Dynamic compression significantly upregulated protein synthesis but did not significantly affect sGAG synthesis with Nf or Tg treatment. Dynamic compression significantly upregulated both protein and sGAG synthesis rates with Gd treatment. There was no significant stimulation of either protein or sGAG synthesis by dynamic compression with 4AP treatment. Interruption of many ion-channel signaling mechanisms affected sGAG synthesis, suggesting a complicated, multi-pathway signaling process. Also, Ca(2+) signaling may be critical for the transduction of mechanical stimulus in regulating sGAG synthesis. This modulation potentially occurs through direct interactions with the extracellular matrix.

54-Year-Old Man With Hip Pain

54-Year-Old Man With Hip Pain

54-Year-Old Man With Hip Pain

54-Year-Old Man With Hip Pain

Effect of GRP75/mthsp70/PBP74/mortalin overexpression on intracellular ATP level, mitochondrial membrane potential and ROS accumulation following glucose deprivation in PC12 cells

Glucose regulated protein 75 (GRP75) is an important molecular chaperon belonged to the heat shock protein (HSP) family. To evaluate the effect of GRP75 overexpression on PC12 cells under glucose deprivation, cell viability and mitochondrial function of GRP75-overexpressing PC12 cells and the vector transfected control PC12 cells were monitored during glucose deprivation. Upon exposure to glucose deprivation, GRP75-overexpressing PC12 cells exhibited more moderate cell damage than control PC12 cells. Both of the two groups of cells showed a decreased ATP level following an early increase in the condition of glucose deprivation, and the mitochondrial potential were also reduced in the similar manner in the two groups of cells. Control PC12 cells showed an immediate and rapid increase in ROS accumulation after the onset of GD treatment, and this accumulation was slowed and reduced in GRP75-overexpressing PC12 cells. These findings suggested that GRP75 could inhibit the ROS accumulation, and it may be associated with the cytoprotective effect of GRP75 overexpression upon glucose deprivation.

Effects of phosphoric acid and glutaraldehyde-HEMA on dentin collagen.

The purpose of this study was to evaluate the effects of phosphoric acid (PA) and a proprietary glutaraldehyde-HEMA aqueous solution (Gluma Desensitizer; GD) on dentin collagen. Specimens of demineralized bovine dentin collagen were treated with either 37% or 50% PA for 1 or 5 min. An additional set of specimens was treated with 37% PA for 1 min followed by GD for 1 min. All specimens were washed with distilled water, lyophilized. reduced with standardized NaB3H4, hydrolyzed with 6 M HCl and subjected to amino acid and cross-link analyses. The results demonstrated that the treatment of demineralized dentin with PA under the conditions tested did not significantly alter the collagen cross-links. The GD-treated samples showed reduction of free lysine (Lys) and hydroxylysine (Hyl) residues, as well as a decrease in the levels of collagen reducible cross-links. In addition, unidentified reducible compounds were detected by high-performance liquid chromatography (HPLC) analysis. These compounds may be derived from cross-links formed between GD-derived aldehyde and Lys/Hyl of collagen. The findings indicate that PA treatment does not significantly affect dentin collagen amino acid and cross-link composition, and that GD treatment affects dentin collagen amino acid and cross-link composition.

Prevention of endotoxin-induced mortality is associated with blockade of both PGE2 synthesis and calcium flux in Kupffer cells

Hepatic Kupffer cells (KC) comprise a major macrophage population responsible for synthesis of the mediators, TNF-a and PGE 2, implicated in septic mortality. The rare earth metal, Gadolinium chloride (Gd), when internalized by KC, inhibits KC phagocytosis and is known to alter Ca ++ flux in other cell types. We examined the effect of Gd on a lethal LPS challenge and the associated effects on PGE 2, [Ca++] i, and TNF-a production by KC. Methods: Rats were injected with either Gd (7mg/kg i.v.) or vehicle for the two days prior to a lethal LPS dose (30mg/kg i.v.) or prior to isolation of KC by collagenase digestion and plastic adherence. Supematants from cultured LPS-stimulated KC were assayed for TNF-a using the L929 bioassay and for PGE 2 by RIA. To determine Ca ++ flux in fura-2-AM-loaded KC, fluorescence changes were measured [using a spectrofluorimeter] after exposure to CaC12, PAF or innomycin in the presence or absence of Gd (1.0 mM). Ca ++dependent (innomycin) or Ca ++ independent (TPA) PGE 2 synthesis by KC were stimulated in the presence or absence of Gd (10 mM).Results: Two doses of Gd in vivo completely protected against the lethal dose of LPS (0% vs. 100% mortality for vehicle control, p<0.001). Gd-treated KC released PGE 2 in response to in vitro LPS (0.025 mg/ml) and exhibited impaired Ca ++ flux when exposed to innomycin. Passive and receptor-mediated influx of Ca ++ after PAF stimulation into Ca++-depleted KC were inhibited by in vitro Gd. Gd treatment reduced the iunomycinmediated, Ca++-dependent pathway of PGE 2 synthesis but did not affect the TPA-mediated, Ca++-independent pathway. In vivo GD treatment significantly (p<0.05) increased TNF-a response (vs decreased PGE 2) to in vitro LPS when compared to control KC. The associated increase of TNF-a by Gd reflects the decrease of autocoid inhibition of TNF-a by PGE 2 and suggests that TNF-a is not directly responsible for septic death.