Effect of passive pile on 3D ground deformation and on active pile response.

Using a series of model tests, this study investigated the effect of a passive pile on 3D ground deformation around a laterally loaded pile and on that laterally loaded pile's response in sand. The active pile head was subjected to lateral loads, and the passive pile was arranged in front of the active pile. In the model tests, the distance between the two pile centers was set to zero (i.e., a single pile test), 2.5, 4, and 6 times the pile width (B). The 3D ground surface deformations around the active and passive piles were obtained using a newly developed Stereo-PIV technique. The experimental results showed that the ground surface movements were restrained by the passive pile when the pile spacing was less than 6B. The response of the active pile was affected by the passive pile when the pile spacing was less than 4B. This study combined the response of the active pile and surrounding 3D ground deformation to investigate the effect of the passive pile, which is useful to further understand the pile-soil-pile interactions and to enhance pile foundation design in engineering practice.

I2-catalyzed synthesis of 3-aminopyrrole with homopropargylic amines and nitrosoarenes.

The synthesis of 3-aminopyrrole using the amination reagent nitrosoarenes and homopropargylic amines catalyzed by I2 through cyclization and amination has been developed. This protocol features excellent functional group tolerance and mild reaction conditions, yielding 3-aminopyrroles in moderate to good yields without a metal catalyst. This method realizes the construction and amination of the 3-aminopyrroles in which nitrosoarenes serve as the amine source and oxidant.

Mechanical and microstructural properties of recycling granite residual soil reinforced with glass fiber and liquid-modified polyvinyl alcohol polymer.

Glass fiber and liquid-modified polyvinyl alcohol polymer (SH Polymer) are used to reinforce granite residual soil. In this paper, scanning electron microscopy (SEM) tests and drop-weight tests were used to study the microscopic interaction mechanism and impact resistance of granite residual soil specimens reinforced by glass fiber and SH Polymer. Combined with the equivalent confining pressure theory, Mohr-Coulomb intensity lines were used to quantitatively analyze the reinforcement effect of glass fiber. The SEM results showed that the granite residual soil solidified by a 3.5 % SH polymer had a tighter bond between the flake clay particles. In addition, with the incorporation of glass fiber, these flake clay particles were cemented on the glass fiber along the long axis, forming a cementing system of flake clay particles and glass fiber. When the glass fiber content was 3.0 %, the impact resistance of the specimen reached its maximum, 32.16 kN. Using the equivalent confining pressure theory, the reinforcement effect of glass fiber on soil could be quantified by Δσ3.

[Effect of combination of insulin and selenium on insulin signal transduction in cardiac muscle of STZ-induced diabetic rats].

This study is to investigate the effect of low doses of insulin (1 u x kg(-1)) and selenium (180 microg x kg(-1)) in combination on general physiological parameters and insulin signal molecules in cardiac muscle of STZ-induced diabetic rats. The levels of blood glucose were estimated using One Touch SureStep Blood Glucose meter. HbA1c levels were estimated using microcolumn assay. TG and TC were estimated using enzymatic assay. The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction.

The influence of chirality, physicochemical properties, and permeation enhancers on the transdermal permeation of amlodipine across rat skin.

PURPOSE: This study was aimed at investigating the possible relationship between the physical properties and the permeation of S-amlodipine and RS-amlodipine and studying the possible enantioselectivity of permeation of amlodipine in the presence and absence of enhancers, such as terpene enhancers and ethanol. METHOD: The solubility of S-amlodipine and RS-amlodipine was measured using the shake-flask method. The thermodynamic properties were investigated by differential scanning calorimetry (DSC). The type of racemate amlodipine was investigated by DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of racemate and enantiomers of amlodipine through rat epidermis in vitro was investigated using the modified Franz diffusion cell. RESULTS: The aqueous solubility of S-amlodipine was higher than that of RS-amlodipine. The melting temperature and enthalpy of fusion of S-amlodipine were lower than those of RS-amlodipine. RS-amlodipine was a racemic compound. The permeation of the enantiomers of amlodipine from RS-amlodipine reservoir showed no significant differences in the presence and absence of enhancers, but the permeation of S-amlodipine from S-amlodipine reservoir was significantly higher than that of RS-amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene enhancers could not influence the difference in permeation between S-amlodipine and RS-amlodipine, but 75% ethanol could reduce the difference. CONCLUSION: These results suggested that there was no enantioselectivity of the enantiomers of amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers, but the differences in physical properties between S-amlodipine and RS-amlodipine led to the difference in permeation across rat skins.

Characterization of ion channels in human preadipocytes.

Ion channels participate in regulation of cell proliferation. However, though preadipocyte (the progenitor of fat cell) is a type of highly proliferating cells, ion channel expression and their role in proliferation is not understood in human preadipocytes. The present study was designed to characterize ion channels using whole-cell patch clamp technique, RT-PCR, and Western blotting. It was found that a 4-aminopyridine- (4-AP) sensitive transient outward K(+) current (I(to)) was present in a small population of (32.0%) cells, and an outward "noisy" big conductance Ca(2+)-activated K(+) current (I(KCa)) was present in most (92.7%) preadipocytes. The noisy current was inhibited by the big conductance I(KCa) channel blocker paxilline (1 microM), and enhanced by the Ca(2+) ionophore A23187 (5 microM) and the big conductance I(KCa) channel activator NS1619 (10 microM). RT-PCR and Western blot revealed the molecular identities (i.e., KCa1.1 and Kv4.2) of the functional ionic currents I(KCa) and I(to). Blockade of I(KCa) or I(to) with paxilline or 4-AP reduced preadipocyte proliferation, and similar results were obtained with specific siRNAs targeting to KCa1.1 and Kv4.2. Flow cytometric analysis showed ion channel blockade or knockdown of KCa1.1 or Kv4.2 with specific siRNA increased the cell number of G0/G1 phase. The present study demonstrates for the first time that two types of functional ion channel currents, I(to) and big conductance I(KCa), are present in human preadipocytes and that these two types of ion channels participate in regulating proliferation of human preadipocytes.

Characterization of calcium signaling pathways in human preadipocytes.

Intracellular free Ca2+ (Ca(i)2+) is an important regulator of many cellular activities; however, Ca2+ signaling is not well studied in human preadipocytes. The purpose of the present study was to characterize Ca2+ signal pathways using a confocal scanning technique and RT-PCR. It was found that spontaneous Ca(i)2+ oscillations were observed in 12.1% preadipocytes, and number of cells with Ca2+ oscillations was increased to 47.9% by 1% fetal bovine serum. Ca(i)2+ oscillations were dependent on Ca2+ entry mainly via stored-operated Ca2+ (SOC) entry. They were suppressed by the SOC entry channel blocker La3+, the phospholipase C (PLC) inhibitor U73122, the inositol trisphosphate receptor (IP3R) blocker 2-amino-ethoxydiphenyl borate, or the sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) inhibitors thapsigargin and cyclopiazonic acid, but not by ryanodine. The IP3R activator thimerosal increased Ca(i)2+ oscillations. In addition, the plasma membrane Ca2+ pump (PMCA) inhibitor carboxyeosin and Na+--Ca2+ exchanger (NCX) inhibitor Ni2+ both suppressed Ca2+ oscillations. RT-PCR revealed that the mRNAs for IP3R1-3, SERCA1,2, NCX3 and PMCA1,3,4, Ca(V)1.2, and TRPC1,4,6, STIM1 and Orai1 (for SOC entry channels) were significant in human preadipocytes. The present study demonstrates that multiple Ca2+ signal pathways are present in human preadipocytes, and provides a basis for investigating how Ca2+ signals regulate biological and physiological activities of human preadipocytes.

Influence of sodium dodecyl sulfate on swelling, erosion and release behavior of HPMC matrix tablets containing a poorly water-soluble drug.

The effect of sodium dodecyl sulfate (SDS) on the swelling, erosion and release behavior of HPMC matrix tablets was examined. Swelling and erosion of HPMC matrix tablets were determined by measuring the wet and subsequent dry weights of matrices. The rate of uptake of the dissolution medium by the matrix was quantified using a square root relationship whilst the erosion of the polymer was described using the cube root law. The extent of swelling decreased with increasing SDS concentrations in the dissolution medium but the rate of erosion was found to follow a reverse trend. Such phenomena might have been caused by the attractive hydrophobic interaction between HPMC and SDS as demonstrated by the cloud points of the solutions containing both the surfactant and polymer. Release profiles of nimodipine from HPMC tablets in aqueous media containing different concentrations of SDS were finally studied. Increasing SDS concentrations in the medium was shown to accelerate the release of nimodipine from the tablets, possibly due to increasing nimodipine solubility and increasing rate of erosion by increasing SDS concentrations in the dissolution medium.

Tanshinone IIA downregulates the CD40 expression and decreases MMP-2 activity on atherosclerosis induced by high fatty diet in rabbit.

Tanshinone IIA (Tan IIA) is a member of the major lipophilic components abstracted from the root of Salvia miltiorrhiza Bunge and has the capacity of anti-atherosclerosis. To investigate the potential mechanism, we established an animal model by giving high fatty diet to rabbits and Tan IIA was given in different dose. Then, superoxide dismutase (SOD) activity and the malondialdehyde (MDA) level in serum were detected using spectrophotometry; cluster of differentiation 40 (CD40) expression of cellular membrane fraction of aortas and matrix metalloproteinase-2 (MMP-2) activity of total protein extract of aortas were detected by Western Blotting and Zymography, respectively. Compared with the control group, the level of MDA, the expression of CD40 and the MMP-2 activity were increased while the SOD activity was decreased significantly in model group. After Tan IIA administration, the SOD activity was significantly increased while the level of MDA was decreased; both the expression of CD40 and the activity of MMP-2 were decreased. It is suggested that Tan IIA not only inhibits the oxidation but also suppresses the inflammation in atherosclerotic lesion. Our data suggest that not only anti-oxidation but also anti-inflammation by decrease the expression of CD40 and MMP-2 activity maybe the potential mechanisms by which Tan IIA anti-atherosclerosis.

Cu-Catalyzed Tandem Aerobic Oxidative Cyclization for the Synthesis of 3,3'-Bipyrroles from the Homopropargylic Amines.

A Cu-catalyzed method for the synthesis of 3,3'-bipyrroles from homopropargylic amines through tandem aerobic oxidative cyclization involving the formation of C-C bond has been developed. The features of this reaction are a small number of Cu catalysis and simple starting substrates. Moreover, this procedure exhibits good functional group tolerance and a series of 3,3'-bipyrroles derivatives are obtained in moderate to good yields.

A non-steroidal anti-inflammatory agent provides significant protection during focal ischemic stroke with decreased expression of matrix metalloproteinases.

The present study was designed to investigate whether the neuroprotective effect of nimesulide was mediated by inhibiting expression of matrix metalloproteinase-9 (MMP-9) and/or matrix metalloproteinase-2 (MMP-2) in a rat model of thrombolytic reperfusion after the embolic focal cerebral ischemia (FCI). It was found that nimesulide at therapeutically relevant doses (3, 6 and 12 mg/kg) decreased neurological deficits, infarct volume, brain index and brain water content in a dose-dependent manner. Hemorrhagic transformation was reduced by 64% with treatment of 12 mg/kg nimesulide. Quantitative analysis of immunohistochemical staining of brain slices showed that the neuron number expressing MMP-9 and MMP-2 increased in the model animals treated with vehicle (p<0.01 vs sham group), and significantly decreased in nimesulide-treated animals (p<0.05 or p<0.01 vs vehicle group). Our results demonstrate that nimesulide significantly reduces the degree of neuronal injury and hemorrhage transformation caused by thrombolytic reperfusion after the embolic FCI, and that inhibition of MMP-9 and MMP-2 expression contributes at least in part to the neuroprotection.

Tanshinone IIA inhibits atherosclerotic plaque formation by down-regulating MMP-2 and MMP-9 expression in rabbits fed a high-fat diet.

Tanshinone IIA (Tan IIA) is one of the major lipophilic components of Salvia miltiorrhiza Bunge (SM) and has an anti-atherosclerotic effect. To investigate the potential mechanism of this effect, we established an atherosclerotic animal model by feeding rabbits a high-fat diet, and Tan IIA was given at different doses. Intimal area of the aorta was measured by image analysis, serum levels of vascular adhesion molecule-1 (VCAM-1) and interleukin (IL-1beta) were measured by ELISA, while matrix metalloproteinase-2 and-9 (MMP-2, MMP-9) expression and their activities in atherosclerotic lesions were assessed by Western blotting and zymography respectively. Compared with the control group, the intimal area, serum levels of VCAM-1 and IL-1beta, the expression of MMP-2 and MMP-9 as well as their activities were increased significantly in the high-fat fed rabbit group. After Tan IIA administration, all of these parameters were decreased in a dose-dependent manner. Our results show that Tan IIA can inhibit atherosclerotic lesion formation in aorta and down-regulate protein expression and activities of MMP-2 and MMP-9 as well as serum VCAM-1 and IL-1beta in rabbits fed a high-fat diet.

Enhanced cAMP/PKA pathway by seabuckthorn fatty acids in aged rats.

Seabuckthorn fatty acids were extracted by crushing and centrifuging from china seabuckthorn fruit. We detected cyclic nucleotides concentration in serum of different stages in aged rats (from 16 to 21 months), cyclic nucleotides concentration, PKA activity and PDE activity in hepatic tissue in aged rats by seabuckthorn fatty acids. Our data showed that the serum cAMP concentration decreased, accompany with the cGMP concentration increased and the imbalance of the cAMP/cGMP ratio in aged process. This kind of change equally in the hepatic tissue, the cAMP concentration decreased, PKA activity also decreased, but no change of the cAMP particularity PDE activity. And the SBFAs raised serum cAMP level in different stages, and raised the cAMP concentration and PKA activity of hepatic tissue, but did not effect the cAMP particularity PDE activity. Our study demonstrated that it is imbalance of the cAMP/cGMP ratio in aged process. SBFAs enhanced the cAMP/PKA pathway, regulated cAMP/cGMP ratio in aged rats.

[Experimental study on effect of tiangui gengnian soft capsule on aged female rats with osteoporosis].

OBJECTIVE: To investigate the effect of Tiangui Gengnian soft capsule (TGC), which mainly consists of seabuckthorn fatty acid, on serum estrogen and estrogen receptor (ER) in multiple target tissues as uterus, liver and bone, in aged female rats, in order to explore its mechanism from the aspects of receptor and cytokines. METHODS: Low (0.72 g/kg), middle (1.80 g/kg) and high (4.50 g/kg) dose of TGC were administered by gastrogavage to young and aged (22 months old) female rats with osteoporosis for 45 days, and diethylstilbestrol (0.02 mg/kg) was used as a positive control. The levels of serum estradiol (E2), transforming growth factor beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassay and ELISA method, the protein expression of their receptor in bone, uterus and liver was detected by SABC immunohistochemistry, and the mRNA expression of E2 in uterus and liver detected by in situ hybridization with digoxin probe. RESULTS: Intervention of TGC could cause increase of serum E2, IGF-1 and TGF-beta1 levels, the TGF-beta1 reached 90.63 +/- 18.71 pg/L in the group administered with high dose, which was significantly different to that in the aged group (P < 0.01). There was no obvious effect of the mRNA expression of E2 in uterus and liver, and no effect of TGF-beta1 and IGF-1 in liver in rats. CONCLUSION: TGC could improve the postmenopausal bone metabolism, alleviate and correct the bone loss, it is possibly realized by way of side-secreting/auto-secreting of E2 receptor and cytokines (TGF-beta1 and IGF-1) to improve the osteogenesis and inhibit the destruction of bone.

[Experimental study on the effect of tiangui gengnian capsule on the aged female rats ostepoprosis].

OBJECTIVE: To study the therapeutic action of Seabuckthorn Fatty Acid on the aged female rats osteoporosis, and explore the corresponding mechanism related in hormone and cytokine. METHODS: The change of bone density (BMD), biomechanics and bone morphology were measured and E2, TGF-beta1, IGF-1 level in plasma were determined respectively for the young female rats, aged female rats (Seabuckthorn Fatty Acid 0.72, 1.8, 4.5 g/kg, E2 0.02 g/kg) after they were administrated corresponding drugs for 45 days. RESULTS: The bone density (BMD), bone biomechanics, bone morphology for female rats aged 22-months all decreased. The BMD, bone biomechanics, the number of bone trabeculas and cortical thickness in Seabuckthorn Fatty Acid treated groups (1.8 g/kg, 4.5 g/kg) were upgraded (P < 0.05). The TGF-beta1, IGF-1 level in plasma were increased, too (P < 0.05). CONCLUSION: Seabuckthorn Fatty Acid can meliorate bone metabolism in post-menopause and heighten the bone density. The adjustment mechanism may be based on the function of estrogen and cell cytokine.

AgNO2 as the NO Source for the Synthesis of Substituted Pyrazole N-Oxides from N-Propargylamines.

A straightforward method for synthesizing the pyrazole N-oxides from N-propargylamines and AgNO2 through oxidation/cyclization reaction had been developed. AgNO2 was used as the NO source for the first time to synthesize pyrazole N-oxides. Various substituted groups on N-propargylamines proceeded smoothly, and the desired products were obtained in good yields.

Protamine zinc insulin combined with sodium selenite improves glycometabolism in the diabetic KKAy mice.

Long-term, high dosage protamine zinc insulin (PZI) treatments produce adverse reactions. The trace element selenium (Se) is a candidate for the prevention of diabetes due to anti-oxidative stress activity and the regulation of glycometabolism. In this study, we aimed to investigate the anti-diabetic effects of a combination of PZI and Se on type 2 diabetes. Diabetic KKAy mice were randomized into the following groups: model group and groups that were subcutaneously injected with PZI, Se, high or low dose PZI + Se for 6 weeks. PZI combined with Se decreased the body weight and fasting blood glucose levels. Moreover, this treatment also improved insulin tolerance, as determined by the reduced values from the oral glucose tolerance test and insulin tolerance test, and increased insulin levels and insulin sensitivity index. PZI combined with Se ameliorated skeletal muscle and ß-cell damage and the impaired mitochondrial morphology. Oxidative stress was also reduced. Furthermore, PZI combined with Se upregulated phosphatidylinositol 3-kinase (PI3K) and downregulated protein tyrosine phosphatase 1B (PTP1B). Importantly, the low dosage combination produced effects similar to PZI alone. In conclusion, PZI combined with Se improved glycometabolism and ameliorated the tissue and mitochondrial damage, which might be associated with the PI3K and PTP1B pathways.

Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane.

To improve selectivity and specificity of cell membrane chromatography (CMC), the chromatography affinities of nine ligands of alpha1-adrenergic receptor(AR)to alpha1D-AR subtype were investigated. The human embryonic kidney (HEK) 293 cells expressed by cDNA of alpha1D-AR subtypes were cultured and cell membrane stationary phase (CMSP) was prepared. Then the interactions between ligands and alpha1D-AR in CMSP were investigated using CMC. The affinity rank order to alpha1D-AR subtype obtained from CMC for the nine alpha1-adrenoceceptor ligands is: prazosin, BMY7378, phentolamine, oxymetazoline, 5-methylurapidil, norepinephrine, phenylephrine, methoxamine, RS-17053. The affinity rank order is similar and correlates well with that obtained from others' radioligand binding assays (RBA). CMSP prepared by transfected HEK293 cells with alpha1-D-adrenoceptor cDNA and CMC method could be used to evaluate affinities of -drug-receptor and drug-receptor subtypes and to screen drugs selective to alpha1D-AR.

Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.

Background. Liraglutide (a glucagon-like peptide 1 analog) was used for the treatment of type 2 diabetes (T2DM) which could produce glucose-dependent insulin secretion. Aim. The aim was to investigate whether liraglutide could improve myofibril and mitochondria injury in skeletal muscle and the mechanisms in diabetic KKAy mice. Method. We divided the male KKAy mice into 2 groups: liraglutide group (250 µg/kg/day liraglutide subcutaneous injection) and model group; meanwhile, the male C57BL/6J mice were considered as the control. After 6 weeks, the ultrastructure of skeletal muscle was observed by electron microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), phosphatidylinositol 3-kinase (PI3K), and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and phospho-Akt2 (p-Akt2) were measured by Western blot. Results. Liraglutide significantly ameliorated the injury of mitochondria by increasing the number (+441%) and the area (+113%) of mitochondria and mitochondrial area/100 µm(2) (+396%) in skeletal muscle of KKAy mice. The results of real-time PCR and Western blot showed that liraglutide downregulated PTP1B while it upregulated PI3K and GLUT4 (P < 0.01). The protein level of p-Akt2/Akt2 was also increased (P < 0.01). Conclusion. These results revealed that liraglutide could improve myofibril and mitochondria injury in skeletal muscle against T2DM via PTP1B and PI3K/Akt2 signaling pathway.