Purpose Antiseptic solutions are commonly used in dentistry for a number of sterilization procedures, including harvesting of bone chips, irrigation of extraction sockets, and sterilization of ...osteonecrotic bone. Despite its widespread use, little information is available regarding the effects of various antiseptic solutions on bone cell viability, morphology, and the release of growth factors. Materials and Methods The antiseptic solutions included 1) 0.5% povidone iodine (PI), 2) 0.2% chlorhexidine diguluconate (CHX), 3) 1% hydrogen peroxide (H2 O2 ), and 4) 0.25% sodium hypochlorite (HYP). Bone samples collected from porcine mandibular cortical bone were rinsed in the antiseptic solutions for 10 minutes and assessed for cell viability using an MTS assay and protein release of transforming growth factor (TGF-β1), bone morphogenetic protein 2 (BMP2), vascular endothelial growth factor (VEGF), interleukin (IL)-1β, and receptor activator of nuclear factor κB ligand (RANKL) using an enzyme-linked immunosorbent assay at 15 minutes and 4 hours after rinsing. Results After antiseptic rinsing, changes to the surface protein content showed marked alterations, with an abundant protein layer remaining on CHX-rinsed bone samples. The amount of surface protein content gradually decreased in the following order: CHX, H2 O2 , PI, and HYP. A similar trend was also observed for the relative cell viability from within bone samples after rinsing, with up to 6 times more viable cells found in the CHX-rinsed bone samples than in the HYP- and PI-rinsed samples. An analysis of the growth factors found that both HYP and PI had significantly lower VEGF and TGF-β1 protein release from bone samples at 15 minutes and 4 hours after rinsing compared with CHX and H2 O2 . A similar trend was observed for RANKL and IL-1β protein release, although no change was observed for BMP2. Conclusions The results from the present study have demonstrated that antiseptic solutions present with very different effects on bone samples after 10 minutes of rinsing. Rinsing with CHX maintained significantly higher cell viability and protein release of growth factors potent to the bone remodeling cycle.
Among four closely related members of the FGF receptor family, FGFR 1, 2, and 3 have alternative splicing forms encoded by different exons for the C-terminal half of the third Ig-like domain, but ...FGFR 4 has no such alternative exon. Furthermore, FGFR 1, 2, and 3 have another splice variant of nontransmembrane type; however, such a variant has not been reported for FGFR 4. While searching for a novel receptor-type tyrosine kinase by RT-PCR, we identified a non-transmembrane-type receptor of FGFR 4 in human intestinal epithelial cell lines (Intestine 407 and Caco-2). Sequence analysis of this receptor revealed that exon 9 coding the single transmembrane domain was displaced by intron 9. Consequently, this variant form was 120 bp shorter than the normal form and had no transmembrane portion. Moreover, the signal sequence in exon 2 was maintained, suggesting that this splice variant is a soluble receptor. This soluble receptor was detected in human gastrointestinal epithelial cells and pancreas, and also in gastric, colon, and pancreatic cancer cell lines. Single cell RT-PCR showed that this soluble receptor was expressed simultaneously with the transmembrane-type receptor in the same cell. Western blot analysis revealed that this receptor was secreted from the transfected COS7 cells. Thus, a soluble-form splice variant of FGFR 4 was identified in human gastrointestinal epithelial cells and cancer cells. This is the first report of alternative splicing of FGFR 4.
Background Patients with lung cancer often present with recurrence, even after resection. The identification of risk factors for recurrence after resection is useful. Methods Among 1,338 patients ...with lung cancer who underwent a complete resection, 277 developed recurrences post surgery. Data regarding the TNM factors, histologic subtype, and presence/absence of vessel invasion were analyzed retrospectively using the survival tree method to identify groups with a high risk of recurrence after resection. Results The results revealed that the T factor, the N factor, and lymphatic (ly) and blood (v) vessel invasion were related to the risk of recurrence, and six combinations of these factors were identified using the survival tree method: group A: v = 0, T ≤ 1b, ly = 0; group B: v = 0, T ≤ 1b, ly ≥ 1; group C: v = 0, T ≥ 2a; group D: v ≥ 1, N ≤ 1, T ≤ 2b; group E: v ≥ 1, N ≤ 1, T ≥ 3; and group F: v ≥ 1, N ≥ 2. The six groups were then further classified into three groups: a low-risk group (group A), a moderate-risk group (groups B, C, and D), and a high-risk group (groups E and F). The 5-year recurrence-free survival rate was approximately 98% for the low-risk group, 75% for the moderate-risk group, and 30% for the high-risk group. Conclusions Combining the T, N, v, and ly factors allowed the precise identification of a group with a high risk of recurrence after resection.
Correction to: Oncogene (2000) 19, 3508–3520. A mistake occurred during the preparation of this manuscript, such that the top panels from Figure 10b and c used data that had been previously published ...in Cell Death and Differentiation. These data are similar in appearance, but was performed without the transfected neomycin-resistant expression vector.
During apoptosis of human glioma cells induced by anti-Fas antibody, ceramide formation with activation of acid, but not neutral sphingomyelinase (SMase), was observed. A potent inhibitor of acid ...SMase, SR33557, effectively inhibited ceramide formation and apoptosis. Fas-induced apoptosis and ceramide formation proceeded regardless of p53 status. The agents, which modify intracellular levels of reactive oxygen species (ROS) and reduced glutathione (GSH), failed to modulate Fas-induced acid SMase activation and apoptosis. Moreover, expression of functional p53 protein using a temperature-sensitive human p53val138 induced ceramide generation by activation of neutral SMase but not acid SMase through ROS formation. Peptide inhibitors for caspases-8 (z-IETD-fmk) and -3 (z-DEVD-fmk) suppressed Fas-induced apoptosis. However, activation of acid SMase was inhibited only by z-IETD-fmk. Thus, ceramide generated by acid SMase may take a part in Fas-induced apoptosis of human glioma cells and acid SMase activation may be dependent on caspase-8 activation, but not on p53 nor ROS.
PII-64 Kumagai, Y.; Fujita, T.; Ozaki, M. ...
Clinical pharmacology and therapeutics,
02/2006, Letnik:
79, Številka:
2
Journal Article
Recenzirano
BACKGROUND
TAS‐108 is a novel steroidal antiestrogen, expected for the treatment of breast cancer. We investigated the safety and pharmacokinetics of single oral dose of TAS‐108 in 12 postmenopausal ...women and effect of food on pharmacokinetics.
METHODS
A single dose of 40mg (step 1) and 120 mg (step 3) of TAS‐108 was administered to six subjects. Another six subjects were administered 80mg (step 2) in fast or fed condition. Plasma concentrations of TAS‐108 and its metabolites (deEt‐TAS‐108 and TAS‐108‐COOH) were measured.
RESULTS
After the oral administration, TAS‐108 was absorbed rapidly at all dose levels. Plasma level of TAS‐108‐COOH was higher than TAS‐108, and that of deEt‐TAS‐108 was the lowest. Cmax and AUC of TAS‐108 and its metabolites increased proportionally to the doses. TAS‐108 disappeared from plasma with elimination half‐lives of 16.9 to 20.3h. AUC and Cmax of TAS‐108 were higher in fed condition by approximately 1.5 times. Adverse events such as edema, hot flush and so on were found in 8 subjects (33.3%) and all of them were of mild severity and transient symptoms that resolved without therapeutic intervention.
CONCLUSIONS
TAS‐108 was well tolerated up to 120 mg in healthy subjects.
Clinical Pharmacology & Therapeutics (2005) 79, P53–P53; doi: 10.1016/j.clpt.2005.12.189
Impaired right ventricular systolic function (RVSF) may complicate the treatment of constrictive pericarditis (CP) by pericardiectomy, which is a procedure that remains with significant morbidity and ...mortality. We evaluated RVSF in patients with CP who underwent pericardiectomy to determine the prognostic value of RVSF. RVSF was assessed by measuring Tricuspid Annular Plane Systolic Excursion (TAPSE) in 35 patients (mean age 52 ± 15.4 years) who underwent pericardiectomy. Thirty-one patients (88.6%) had reduced RVSF (TAPSE ≤1.8 cm). Eight patients (23%) had postoperative events (heart failure 3 and hospital mortality 5). Logistic regression showed that concomitant coronary artery bypass grafting (CABG) (p = 0.052), left ventricular ejection fraction (p = 0.059), left atrial diameter (p = 0.028), and TAPSE (p = 0.016) were borderline or significant univariate predictors of events. TAPSE (p = 0.018, odds ratio = 0.605 0.40 to 0.92) and CABG (p = 0.033, odds ratio = 20 1.26 to 315) were independent predictors of events on multivariate analysis. Stepwise analysis showed that TAPSE provided incremental prognostic value (p = 0.029, chi-square increase 11.6 to 16.3) to the combination of CABG, ejection fraction, and left atrial diameter. Receiver-operating characteristic curve analysis showed an area under the curve of 0.815 for TAPSE. TAPSE of 1.38 cm had a sensitivity of 88% and specificity of 67% for identifying patients with events. TAPSE was also inversely related to the length of hospital stay after pericardiectomy (p = 0.02, R = −0.424). Hence, our study showed that RVSF is frequently reduced in patients with CP who underwent pericardiectomy. In conclusion, TAPSE is an independent predictor of events and provides incremental prognostic value to other clinical and echocardiographic variables.
Inhibitors of thymidine phosphorylase (dThdPase) are expected to suppress the growth and metastasis of tumor cells by inhibition of angiogenesis and were designed by utilizing the three dimensional ...structure of the enzyme. 5-Substituted 6-aminouracils (5) and 7-substituted pyrrolo2,3-dpyrimidine-2,4-diones (6) were synthesized and tested for inhibition of human placenta thymidine phosphorylase. 5-Bromo-6-aminouracil (5d), 5-cyano-6-3-(methylamino)propyl-uracil (5e), and 7-(2-aminoethyl)-pyrrolo2,3-dpyrimidine-2,4-dione (6c) inhibited dThdPase with IC50s of 7.6, 3.8 and 44.0 microM, respectively.
A 43-year-old man was admitted because of gingival bleeding. A diagnosis of acute promyelocytic leukemia (APL) was made. He was given combination chemotherapy including all-trans retinoic acid ...(ATRA). During the myelosuppression stage, the patient developed Fournier's gangrene of the scrotum. He achieved complete remission and underwent a hemicastration procedure. Seven months later, bilateral external ear tumors developed. Biopsy specimens of the tumors revealed infiltration of APL cells. A second remission was obtained by chemotherapy including ATRA. However, bilateral ear tumors developed again 5 months later despite indications of normal marrow without proliferation of leukemic blasts. Irradiation successfully reduced the ear tumors, but the patient died of cerebral hemorrhage from a left frontal extramedullary tumor. This was a rare case of APL accompanied by Fournier's gangrene of the scrotum during ATRA treatment, and by extramedullary tumors of the external ear and brain during leukemic relapse.
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