AIMTo determine the effect of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uteri in ovariectomized rats.

METHODSFemale Sprague-Dawley rats were ovariectomized (OVX) or sham operated (sham) at the age of 3 months and treated with estrone (E) at 0.75 mg.kg-1.d-1, or with piperazinyl estrone (P-E) at 1 or 10 mg.kg-1.d-1, orally, for 3 months. At the time of death, the uterine weight was measured. Bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections.

RESULTSBone histomorphometric data showed that the percent trabecular area (% Tb.Ar) of OVX rats with bone high turnover was significantly decreased. The uteri were atrophied. The percent trabecular area (% Tb.Ar) of estrone treated group was increased in decreasing bone turnover manner. But the size and weight of uteri in this group were increased vs OVX group. The bone loss induced by OVX was preserved by P-E treatment, but the mechanism of maintaining bone is different from that of E-treated rats. P-E treatment in low dose did not decrease any bone formation indices, such as percent labeling perimeter, bone formation rate per bone volume (BFR/BV), except bone mineral apposition rate (MAR) compared with E-treated group, and maintained them at OVX level. The uteri were found to be in atrophy compared with the match dose (0.75 mg) of E-treated OVX rats. But rats treated with high dose of P-E showed the same change like E-treated group.

CONCLUSIONThe finding of this study shows that lower dosage of piperazinyl estrone has effect on preventing the bone losses in OVX rats, while the bone formation and the uterus are not affected, thus supporting the hypothesis that piperazinyl estrone has the potential to prevent postmenopausal bone loss in women with less side effects.

Animals ; Atrophy ; prevention & control ; Bone Density ; Estradiol Congeners ; pharmacology ; therapeutic use ; Estrone ; analogs & derivatives ; pharmacology ; therapeutic use ; Female ; Organ Size ; drug effects ; Osteogenesis ; drug effects ; Osteoporosis ; prevention & control ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Uterus ; pathology

Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

OBJECTIVETo develop a three-dimensional (3D) finite element model of the human ankle with fine details and analyze the stress distribution on the talus during different gait phases.

METHODSMimics13.0 and Geomagic10.0 software were used for geometric reconstruction of the ankle based on the 3D CT data of the foot. The model was meshed and assigned with the material properties in Hypermesh10.0 software. The model was then imported to Abaqus6.9, and the stress condition of the talus during the 3 phases (heel-strike, midstance, push-off) of normal gait was simulated to calculate the stress distribution within the bone.

RESULTSThe three-dimensional finite element model of the ankle established consisted of 21 865 nodes and 73 440 elements. The stress distribution within the bone in 3 phases of normal gait differed significantly. The peak von Mises stress on the talus dome, from the heel-strike to push-off phases, was 3.0 MPa, 4.3 MPa and 4.8 MPa, as compared to 1.3 MPa, 1.9 MPa and 2.8 MPa on the talar neck, 2.8 MPa, 3.0 MPa, and 3.4 MPa on the talonavicular joint surface, and 2.2 MPa, 1.8 MPa and 1.5 MPa on the subtalar joint, respectively.

CONCLUSIONThe finite element model of the talus shows a good response against the experimental data and can be used to simulate the biomechanic experiment of the talus.

Adult ; Biomechanical Phenomena ; Finite Element Analysis ; Gait ; physiology ; Humans ; Male ; Models, Theoretical ; Software ; Stress, Mechanical ; Talus ; anatomy & histology ; physiology

OBJECTIVETo study the drug resistance changes in Tca8113 cell lines by exposing to carboplatin.

METHODSThe concentration of carboplatin added to Tca8113 cells was increased gradually and continually, which was to induce the carhoplatin-resistance in Tca8113 cells. The sensibility to drugs of the cells was analyzed by MTT method. Immunocytochemistry and RT-PCR were utilized to examine the expression of multidrug resistance proteins and genes.

RESULTSAfter exposing to carboplatin, the Tca8113/CBP cells had higher drug-resistance to CBP, MTX, PYM, VCR and higher expression of MRP, GST-pi than Tca8113 cells.

CONCLUSIONMultidrug resistance of Tca8113/CBP is associated with over expression of MRP, GST-pi and MDR. Tca8113/CBP can provide an ideal model for multidrug resistance research.

Antineoplastic Agents ; Cell Line ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans

OBJECTIVETo clone and identify MF-1 gene which responded to extremely low frequency magnetic fields(ELF MF) in Daudi cells, and explore the response universality of MF-1 gene in several MF-sensitive cell lines, so as to provide experimental basis for revealing the mechanism of biological effects induced by magnetic field.

METHODSThe DNA fragment of MF-1 was cloned and sequenced; the mRNA level of MF-1 gene were analysed in MF-sensitive cell lines(HL-60, L1210 and CHL) by Northern blot after these cells being treated with 0.1 mT and 0.8 mT MF for 20 minutes and 24 hours, respectively.

RESULTSThe MF-1 cDNA sequence had 100% homology with cytochrome oxidase subunit 1 gene(CO1) by searching Gene Bank database; the transcription of CO1 in HL-60, L1210 and CHL cell lines which exposed to 0.1 mT and 0.8 mT MF for 20 minutes were significantly lower(0.38 +/- 0.12 and 0.37 +/- 0.04) than that of control(0.58 +/- 0.12) and so did for 24 hours exposure(0.46 +/- 0.09 and 0.45 +/- 0.09 vs 0.65 +/- 0.06) (P < 0.05).

CONCLUSIONCO1 is a MF-responsive gene. Cytochrome oxidase activity may be affected through low level of CO1 transcription by magnetic fields, thus induce bioeffects in organisms.

Animals ; Cricetinae ; Electron Transport Complex IV ; genetics ; metabolism ; radiation effects ; HL-60 Cells ; Humans ; Leukemia L1210 ; Magnetics ; Mice ; Protein Subunits ; RNA, Messenger ; analysis ; Transcription, Genetic ; radiation effects

OBJECTIVETo measure the osteogenesis and adipogenesis potentiality of rat marrow stromal cells (MSCs) derived from 3, 6, 9, 12-month-old doner rats.

METHODSRat MSCs were induced to osteoblast or adipocyte by osteogenic inducer or adipogenic inducer. In different times, 3 and 12-month-old rat MSCs were observed by histochemistry staining; the mRNA level of type I collagen and lipoprotein lipase of 3, 6, 9, 12-month-old rat MSCs were measured by RT-PCR.

RESULTSThe expression of alkaline phosphatase (ALP) of the control group and induced group of 12-month old rat MSCs was less than that of 3-month old rat MSCs after 1-week osteogenic induction. 12 days later, calcification was observed in 3-month old group. Lipid droplets occurred in the cells of 12-month old group after 2-day adipogenic induction, while these droplets occurred after 3-day or 4-day induction in 3-month old group. The mRNA level of type I collagen decreased with the increase of age. The mRNA level of lipoprotein lipase of younger rats was lower than that of older rats. Both of the changes were more significantly with the increase of the induction time.

CONCLUSIONSWith the increase of age, the ability of osteogenesis of rat MSCs decreased, but the ability of adipogenesis increased.

Adipose Tissue ; growth & development ; Aging ; Alkaline Phosphatase ; metabolism ; Animals ; Base Sequence ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Collagen Type I ; biosynthesis ; genetics ; Female ; Lipoprotein Lipase ; biosynthesis ; genetics ; Molecular Sequence Data ; Osteogenesis ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Stromal Cells ; cytology

OBJECTIVETo explore the effect of millimeter wave (MW) at low power density on gap junctional intercellular communication (GJIC) in human keratinocytes (HaCaTs).

METHODSFluorescence recovery after photobleaching (FRAP) technique was employed to determine effect of 30.16 GHz MW exposure at 1.0 and 3.5 mW/cm(2) on GJIC with laser confocal scanning microscope.

RESULTSFRAP analysis revealed that 12-O-tetradecanoylphorbol-13-acetate (TPA) at a dose of 5 microg/L could inhibit GJIC in HaCaTs. Fluorescence recovery rate fell from (55 +/- 17)% in the controls to (34 +/- 13)% after photobleaching, with a very significant difference (P < 0.001). Exposure to MW alone for one hour at either 1.0 mW/cm(2) or 3.5 mW/cm(2) did not affect GJIC, with fluorescence recovery rates of (52 +/- 16)% and (50 +/- 17)%, respectively. GJIC suppression induced by TPA was weakened by MW combined with 5 microg/L TPA treatment for one hour, which could be partially recovered by exposure to 1.0 mW/cm(2) MW with fluorescence recovery rate of (47 +/- 16)%, P < 0.01, and fully recovered by exposure to 3.5 mW/cm(2) MW with fluorescence recovery rate of (50 +/- 16)%, P < 0.001, with a very significant difference.

CONCLUSIONSGJIC suppression induced by TPA could be eliminated or diminished by exposure to millimeter wave in HaCaTs.

Cell Communication ; drug effects ; radiation effects ; Cell Line ; Fluorescence Recovery After Photobleaching ; methods ; Gap Junctions ; drug effects ; physiology ; radiation effects ; Humans ; Keratinocytes ; cytology ; physiology ; Microwaves ; adverse effects ; Tetradecanoylphorbol Acetate ; pharmacology

OBJECTIVETo explore the effect of millimeter wave exposure at low power density on gene expression in human keratinocytes (HaCaT).

METHODSHaCaT keratinocytes were exposed to 30.16 GHz millimeter wave with power densities of 1.0 or 3.5 mW/cm2 for 30 min per day. Gene expression profiles were obtained using the Affymetrix human genome U95A GeneChip. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to confirm the differential expression of genes obtained from Genechip analysis.

RESULTPAR-2 and ERGIC-53 genes in HaCaT cells were up-regulated by 3.5 mW/cm2 millimeter wave exposure for 4 times. ERGIC-53 gene was also up-regulated by 1.0 mW/cm2 millimeter wave exposure for 4 times. However, no significant change for PAR-2 expression was found after the same exposure.

CONCLUSIONMillimeter wave exposure could affect gene expression in human keratinocytes, which might be related to the intensity and the times of exposure.

Cells, Cultured ; Dose-Response Relationship, Radiation ; Electromagnetic Fields ; Gene Expression ; radiation effects ; Humans ; Keratinocytes ; metabolism ; radiation effects ; Mannose-Binding Lectins ; genetics ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Microwaves ; Radiation ; Receptor, PAR-2 ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Skin ; cytology

OBJECTIVETo investigate the relationship among a 50 Hz magnetic field (MF)-induced epidermal growth factor receptor (EGFR) clustering,lipid rafts and acid sphingomyelinase (ASM), and to explore its possible mechanism.

METHODSHuman amnion FL cells were exposed to 50 Hz, 0.4 mT MF for 15 min. EGF treatment was used as positive control. Nystatin was employed to study lipid rafts since it could disrupt lipid rafts structure.The EGF receptors, ASM and lipid rafts were labeled with polyclonal anti-EGFR antibody, anti-ASM antibody and FITC-Cholera toxin B, respectively. The images were observed by laser confocal scanning microscope.

RESULTBoth EGF treatment and 50 Hz MF exposure could induce EGFR clustering; however, nystatin pretreatment disrupted this effect. MF exposure turned ASM (labeled with Cy3) from a diffused state in the sham exposure group to a concentrated state on the cell membrane, which co-localized with lipid rafts (labeled with FITC).

CONCLUSIONThe results suggest that the EGFR clustering induced by 50 Hz MF depends on intact lipid rafts on cellular membrane, and the ASM might participate in the process of EGFR clustering.

Cell Membrane ; radiation effects ; Cells, Cultured ; Electromagnetic Fields ; Epidermal Growth Factor ; metabolism ; Humans ; Membrane Microdomains ; radiation effects ; Receptor, Epidermal Growth Factor ; metabolism ; radiation effects ; Signal Transduction ; physiology ; radiation effects ; Sphingomyelin Phosphodiesterase ; metabolism

Objective To evaluate the availability of tonsillectomy in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) staged as Friedman Ⅰ.Methods Fifty-six patients with OSAHS in Friedman stage Ⅰ who refused uvulopalatopharyngoplasty (UPPP) received tonsillectomy merely from January 2004 to March 2010.There were 20 mild,24 moderate and 12 serious patients respectively in this group.The other 68 OSAHS patients in Friedman stage Ⅰ received UPPP at the same time as matched group,including 26 mild,28 moderate and 14 serious patients.Results There was no significant difference before operation in terms of age,body mass index,apnea hypopnea index ( AHI),the lowest pulse oxygen saturation ( SPO2 ) and average SPO2 between the two groups.There were significant difference in mean length of operation( U =0.000,P ＜0.01 ),hospitalization day( U =458.5,P ＜0.01 ),visual analogue scale after surgery( U =0.000,P ＜ 0.01 ) in these two group.There was no significant difference in surgical effective rate between the two groups ( x2 =0.857,P ＞ 0.05 ).There was also no significant difference in terms of age,body mass index,AHI,the lowest SPO2 and average SPO2 after operation between the two groups (t test P ＞ 0.05).The surgical effective rate for the long term of the two groups was equal ( x2 =0.857,P ＞ 0.05).Even patients with serious OSAHS in Friedman stage Ⅰ,the surgical effective rate of the two groups was equivalent (Fisher's exact test,P ＞ 0.05 ).Conclusions Tonsillectomy is a safe and effective surgery for OSAHS in Friedman stage Ⅰ,whose main structural load lies in the hypertrophic tonsil. It should be the first surgical choice for OSAHS in Friedman stage Ⅰ.