Biomedical subjects

Jie Zhang

Publications and source records attributed to Jie Zhang.

At least 55 records · Page 3Linked to original sources

PubMed2006

Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors.

A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the l-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC(50)=5.2-9.7nM) and could be used as lead compounds in the future.

Caffeic Acids↗

PubMed2006

Proton acceleration from microdroplet spray by weakly relativistic femtosecond laser pulses.

Angular distribution of protons is measured from ethanol droplet spray irradiated by linearly polarized 150 fs laser pulses at an intensity of 1.1 x 10(16)W/cm2. Fast protons (with energies >16 keV ) with an anisotropic distribution can be observed only in or near the polarization plane of the laser fields, while the slow protons (with energies <or=16 keV ) emit with nearly an isotropic distribution. Two-dimensional particle-in-cell simulations suggest that three groups of protons originate from different acceleration regimes in the laser-droplet interaction. The first group with the highest energies is accelerated backwards by the anisotropic charge-separation field near the front surface (laser-droplet interaction side) due to the resonance absorption; the second group (forward emission) is generated by the target-normal sheath acceleration mechanism; and the third group, with the lowest energies, is accelerated by the hydrodynamic expansion of the droplet plasmas.

Journal Article↗

PubMed2006

Novel agonist monoclonal antibodies activate TrkB receptors and demonstrate potent neurotrophic activities.

Tyrosine kinase receptor B (TrkB) mediates neurotrophic effects of brain-derived neurotrophic factor (BDNF) to increase neuronal survival, differentiation, synaptic plasticity, and neurogenesis. The therapeutic potential of TrkB activation using BDNF has been demonstrated well in several preclinical models of CNS diseases, validating TrkB as a promising drug target. Therefore, we aimed to develop TrkB-specific receptor agonists by using a monoclonal antibody approach. After generation of hybridoma clones and assessment of their binding and functional activity, we identified five mouse monoclonal antibodies that show highly selective binding to TrkB and that induce robust activation of TrkB signaling. Epitope mapping studies using competition analysis showed that each of the monoclonal antibodies recognizes a unique binding site on TrkB, some of which are distinct from BDNF docking sites. These antibodies behave as true agonists based on their ability to both activate proximal and secondary signaling molecules downstream of TrkB receptors and promote neuronal survival and neurite outgrowth. The binding affinities and the functional efficacy of these antibodies are comparable to those of BDNF, whereas they do not bind to the p75 low-affinity neurotrophin receptor at all. Therefore, they could represent novel reagents to explore the pathophysiological roles of TrkB and its potential therapeutic utility in treating CNS disorders.

Animals↗

PubMed2006

Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells.

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.

Abietanes↗

PubMed2006

Non-viral delivery of nuclear factor-kappaB decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key transcriptional regulator of inflammatory bowel disease (IBD). AIM: To investigate the therapeutic potential of a locally administered "non-viral" nuclear factor-kappaB decoy (NFkappaBD) in multiple experimental models of IBD. METHODS: A fully phosphorothioated decoy oligonucleotide with improved stability that specifically binds NF-kappaB and blocks inflammatory mediators regulated by this transcription factor without the help of viral envelope-assisted delivery was developed. The therapeutic effects of NFkappaBD were studied in the trinitrobenzene sulphonic acid, oxazolone and dextran sodium sulphate induced colitis models. RESULTS: Intracolonic administration of NFkappaBD results in the delivery of NFkappaBD to inflammatory cells and a reduction of NF-kappaB heterodimers. In the T helper cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice receiving NFkappaBD treatment exhibit a dose-dependent reduction in disease severity and a more rapid recovery to normal body weight, similar to a clinically relevant dose of budesonide. Clinical efficacy was corroborated by considerable reductions in colitis pathology and tissue levels of several pro-inflammatory markers, including tumour necrosis factor alpha, interleukin 6, interleukin 1beta and monocyte chemotactic protein 1. NFkappaBD also mitigates disease activity in the T helper cell 2-like oxazolone colitis and epithelial injury-related acute dextran sodium sulphate colitis models. Interestingly, restoration of tissue homeostasis is observed in NFkappaBD-treated animals with the rapid re-emergence of functional goblet cells and a return to normal patterns of cell proliferation in the mucosal epithelium and smooth muscle cell layers. CONCLUSIONS: These data support the potential use of "naked" NFkappaBD as a cross-functional therapeutic in IBD, and show for the first time that it can facilitate the restoration of colon homeostasis and function.

Animals↗

PubMed2006

Diverse CD81 proteins support hepatitis C virus infection.

Hepatitis C virus (HCV) entry is dependent on CD81. To investigate whether the CD81 sequence is a determinant of HCV host range, we expressed a panel of diverse CD81 proteins and tested their ability to interact with HCV. CD81 large extracellular loop (LEL) sequences were expressed as recombinant proteins; the human and, to a low level, the African green monkey sequences bound soluble HCV E2 (sE2) and inhibited infection by retrovirus pseudotype particles bearing HCV glycoproteins (HCVpp). In contrast, mouse or rat CD81 proteins failed to bind sE2 or to inhibit HCVpp infection. However, CD81 proteins from all species, when expressed in HepG2 cells, conferred susceptibility to infection by HCVpp and cell culture-grown HCV to various levels, with the rat sequence being the least efficient. Recombinant human CD81 LEL inhibited HCVpp infectivity only if present during the virus-cell incubation, consistent with a role for CD81 after virus attachment. Amino acid changes that abrogate sE2 binding (I182F, N184Y, and F186S, alone or in combination) were introduced into human CD81. All three amino acid changes in human CD81 resulted in a molecule that still supported HCVpp infection, albeit with reduced efficiency. In summary, there is a remarkable plasticity in the range of CD81 sequences that can support HCV entry, suggesting that CD81 polymorphism may contribute to, but alone does not define, the HCV susceptibility of a species. In addition, the capacity to support viral entry is only partially reflected by assays measuring sE2 interaction with recombinant or full-length CD81 proteins.

Amino Acid Sequence↗

PubMed2006

Ganglioside GM2 modulates the erythrocyte Ca2+-ATPase through its binding to the calmodulin-binding domain and its 'receptor'.

We have previously demonstrated that gangliosides were able to modulate the plasma membrane Ca2+-ATPase (PMCA) from porcine brain synaptosomes and porcine erythrocytes [Y. Zhao, X. Fan, F. Yang, X. Zhang, Arch. Biochem. Biophys. 427 (2004) 204-212 and J. Zhang, Y. Zhao, J. Duan, F. Yang, X. Zhang, Arch. Biochem. Biophys. 444 (2005) 1-6]. The results indicated that the PMCA from porcine erythrocytes responded to gangliosides was different from that from synaptosomes, suggesting that the effects of gangliosides on the PMCA are isoform specific. Most interestingly, GM2 activated the PMCA from porcine erythrocytes at lower concentrations, but inhibited it at higher concentrations. In the present study, we found that GD1b, GM1 and GM3 did not affect the calpain digested PMCA from porcine erythrocytes or the intact enzyme in the presence of calmodulin, while GM2 inhibited it. Moreover, a synthetic peptide of 17 amino acid residues corresponding to the 'receptor' of the calmodulin-binding domain of the enzyme interfered with the inhibition of the enzyme by GM2 in competition assays. Taken together, our results suggested that gangliosides GD1b, GM1, GM2 (lower concentrations) and GM3 stimulated the PMCA by the interaction with calmodulin-binding domain, while the interaction of GM2 with the 'receptor' of the calmodulin-binding domain of the enzyme led to the inhibition of the enzyme.

Animals↗

PubMed2006

Two cobalt(II) 5-aminoisophthalate complexes and their stable supramolecular microporous frameworks.

Two stable supramolecular microporous cobalt(II) polymers, namely [Co(HAIP)2]n.3nH2O (1) and [Co(AIP)(H2O)]n (2), AIP = 5-aminoisophthalate, were hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, thermogravimetric analyses, and variable-temperature magnetic susceptibility measurements. The two complexes are constructed from the same Co2(CO2)2 SBU, which is extended into a 1D chain in 1 and a 2D layer in 2. As a result, 1 and 2 are 2D and 3D coordination polymers, respectively. The 3D supramolecular network of complex 1 is held up by strong hydrogen bonds formed between carboxylate groups and shows very high stability when the free H2O molecules are removed, indicating an extraordinarily stable H-bonding system. Upon water ligands being liberated, complex 2 becomes a stable microporous solid with coordination-unsaturated Co centers. The behavior of the susceptibility curve of 1 suggests the occurrence of an interesting intrachain antiferromagnetic coupling between the Co(II) ions and the presence of a significant orbital contribution, whereas the features of 2 indicate an antiferromagnetic coupling with T(N) = 3.5 K and a long-range antiferromagnetic order with a field-induced magnetic transition.

Cobalt↗

PubMed2006

Separation and identification of compounds in Adinandra nitida by comprehensive two-dimensional liquid chromatography coupled to atmospheric pressure chemical ionization source ion trap tandem mass spectrometry.

A comprehensive two-dimensional liquid chromatographic (2D-LC) separation system based on the combination of a CN column and a Merck Chromolith Flash reversed-phase column was developed for the separation of components in Adinandra nitida, one type of traditional Chinese medicine (TCM). The two dimensions were connected by a ten-port, dual-position valve controlled automatically by software written in-house. The effluents were detected by both ultraviolet and atmospheric pressure chemical ionization source ion trap tandem mass spectrometry (MS). The calculated peak capacity of the 2D-LC-MS/MS system was above 1240. More than 57 components were resolved in the methanol extract from Adinandra nitida leaves, and five of these were identified based on their relative retention times, molecular weights and MS/MS spectra.

Chromatography, High Pressure Liquid↗

PubMed2006

Prolonged mild hypoxia alters fetal sheep electrocorticogram activity.

OBJECTIVE: To assess the effects of prolonged mild hypoxemia on fetal brain electrocorticogram (ECoG) in late gestation. STUDY DESIGN: Fetal and maternal catheters were placed under general anesthesia and animals allocated at random to receive intratracheal maternal administration of either nitrogen (n = 8) or compressed air (n = 8). Five days after surgery (125 days' gestational age), nitrogen infusion was adjusted to reduce fetal brachial artery PO2 by 25%. The targeted decrease in fetal oxygenation was maintained for 5 days while fetal ECoG activity and fetal and maternal cardiovascular variables were continuously recorded. Data are presented as mean +/- SEM and were analyzed by two-way analysis of variance (ANOVA) or two-sample t test. RESULTS: Nitrogen infusion decreased fetal Po2 by 26% (20.5 +/- 1.7 versus 14.3 +/- 0.8) without changing fetal PCO2 or pH. Mild fetal hypoxemia was associated with fetal tachycardia and increased fetal blood pressure (P < .05). Fetal ECoG in hypoxic fetuses showed a significant decrease in the time spent in high voltage (HV) (P < .05) and an increase in the time spent in low voltage (LV) and in the number of low voltage events (P < .05). Also, a significant decrease in the proportion of 1-4 Hz and an increase in the proportion of 13-20 Hz frequencies was observed in LV events without a significant change in the frequency profile of HV events (P < .05). CONCLUSION: Prolonged mild hypoxemia significantly altered fetal homeostasis as reflected by the sustained tachycardia and increased blood pressure. Fetal ECoG activity was affected significantly in a qualitatively and quantitative manner by mild prolonged hypoxemia.

Animals↗

PubMed2006

Reactivity of lanthanocene hydroxides toward ketene, isocyanate, lanthanocene alkyl, and triscyclopentadienyllanthanide complexes.

The reactivity of [Cp(2)Ln(mu-OH)(THF)]2 (Ln = Y (1), Er (2), Yb (3)) toward PhEtCCO, PhNCO, Cp3Ln, [Cp2Ln(mu-CH3)]2, and the LiCl adduct of Cp2Ln(n)Bu(THF)x was examined. In all cases, OH-centered reactivity is observed: complexes 1-3 react with PhEtCCO to form the O-H addition products [Cp2Ln(mu-eta1:eta2-O2CCHEtPh)]2 (Ln = Yb (5), Er (6), Y (7), respectively, for 1-3), whereas treatment of 1 with PhNCO affords the addition/CpH-elimination/rearrangement product [{Cp2Y(THF)}2(mu-eta2:eta2-O2CNPh)] (8), which contains an unusual PhNCO(2) dianionic ligand. Analogous compound [Cp2Ln(THF)]2(mu-eta2:eta2-O2CNPh) (Ln = Yb (9), Er (10)) and 8 can be obtained in a higher yield by treatment of [Cp2Ln(mu-OH)(THF)]2 with PhNCO followed by reaction with the corresponding Cp3Ln. However, attempts to prepare the corresponding heterobimetallic complex by reacting stoichiometric amounts of [Cp2Y(mu-OH)(THF)]2 with PhNCO followed by treating it with Cp3Yb are unsuccessful. Instead, only rearrangement products 8 and 9 are obtained. Furthermore, the reaction of 3 with [Cp2Yb(mu-CH3)]2 or Cp3Yb forms oxo-bridged compound [Cp2Yb(THF)]2(mu-O) (11), whereas the reaction of [Cp2ErCl]2 with Li(n)Bu followed by treatment with 2 affords unexpected mu-oxo lanthanocene cluster (Cp2Er)3(mu-OH)(mu3-O)(mu-Cl)Li(THF)4 (12). In contrast to 1 and 2, 3 shows a strong tendency to undergo the intermolecular elimination of CpH at room temperature, giving trinuclear species [Cp2Yb(mu-OH)]2[CpYb(THF)](mu3-O) (4). The single-crystal X-ray diffraction structures of 1, 2, and 4-12 are described. All the results offer an interesting contrast to transition- and main-metal hydroxide complexes.

Journal Article↗

PubMed2006

Molecular reorganization of rod-coil diblock copolymers at the air-water interface.

Amphiphilic rod-coil diblock copolymers consisting of flexible poly(ethylene oxide) (PEO) and rodlike poly{(+)-2,5-bis[4'-((S)-2-methylbutoxy)phenyl]styrene} (PMBPS) with predominant hydrophobic contents formed ordered monolayers at the air-water interface. The structures of monolayers transferred to a mica substrate at different surface pressures by the Langmuir-Blodgett method were investigated by atom force microscopy (AFM). For PEO(104)-b-PMBPS(17) copolymer (the subscripts denote the number-averaged polymerization degree of each block), a complete spectrum of molecular reorganization at variable surface pressures was observed. Spherical surface aggregates of LB monolayers were spontaneously formed during the solvent evaporation after the deposition of polymer solution. Continuous compression led to the pancake-to-brush conformation transition of the copolymer that PEO chains desorbed from the air-water interface and went into the water subphase. The effective content of the rod block changed continuously from 61% at zero pressure to 93% at the start of the monolayer collapse, igniting the molecular reorganization. As a result, coalescence of individual spherical aggregates into long cylindrical aggregates with an increase of the surface pressure was observed. For a series of block copolymers PEO(104)-b-PMBPS(m)() (m = 17, 30, 45, 53), as the rod contents increased from 61% to 83%, the morphological transition from spherical aggregates to long cylindrical aggregates in orientational order developed at zero pressure, which showed a similar dependence on the effective contents of the rod block to PEO(104)-b-PMBPS(17) at different pressures. In comparison to coil-coil block copolymers PEO-b-PS, the rod-coil block copolymers PEO-b-PMBPS exhibited distinct structure reorganization behavior, in which the orientation of rod block might play an important role.

Journal Article↗

PubMed2006

Conformational identification of tryptamine embedded in superfluid helium droplets using electronic polarization spectroscopy.

We report electronic polarization spectroscopy of tryptamine embedded in superfluid helium droplets. In a dc electric field, dependence of laser induced fluorescence from tryptamine on the polarization direction of the excitation laser is measured. Among the three observed major conformers A, D, and E, conformers D and E display preference for perpendicular excitation relative to the orientation field, while conformer A is insensitive to the polarization direction of the excitation laser. We attribute the behavior of conformer A to the fact that the angle between the permanent dipole and the transition dipole is close to the magic angle. Using a linear variation method, we can reproduce the polarization preference of the three conformers and determine the angle between the transition dipole and the permanent dipole. Since the side chain exerts small effect on the direction of the transition dipole in the frame of the indole chromophore, all three conformers have a common transition dipole more or less in the indole plane at an angle of approximately 60 degrees relative to the long axis of the chromophore. The orientation of the side chain, on the other hand, determines the size and direction of the permanent dipole, thereby affecting the angle between the permanent dipole and the transition dipole. For conformer D in the droplet, our results agree with the Anti(ph) structure, rather than the Anti(py) structure. Our work demonstrates that polarization spectroscopy is effective in conformational identification for molecules that contain a known chromophore. Although coupling of the electronic transition with the helium matrix is not negligible, it does not affect the direction of the transition dipole.

Journal Article↗

PubMed2006

Poly(ADP-ribose) glycohydrolase activity mediates post-traumatic inflammatory reaction after experimental spinal cord trauma.

The aim of the present study was to examine the role of poly-(ADP-ribose) glycohydrolase (PARG) on the modulation of the inflammatory response and tissue injury associated with neurotrauma. Spinal cord trauma was induced in wild-type (WT) mice by the application of vascular clips (force of 24 g) to the dura via a two-level T(6) to T(7) laminectomy. Spinal cord injury in WT mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, apoptosis, and disease. The genetic disruption of the PARG gene in mice or the pharmacological inhibition of PARG with GPI 16552 [N-bis-(3-phenyl-propyl)9-oxo-fluorene-2,7-diamide] (40 mg/kg i.p. bolus), a novel and potent PARG inhibitor, significantly reduced the degree of spinal cord inflammation and tissue injury (histological score), neutrophil infiltration, cytokine production (tumor necrosis factor-alpha and interleukin-1beta), and apoptosis. In a separate experiment, we have clearly demonstrated that PARG inhibition significantly ameliorated the recovery of limb function. Taken together, our results indicate that PARG activity modulates the inflammatory response and tissue injury events associated with spinal cord trauma and participate in target organ damage under these conditions.

Animals↗

PubMed2006

Cyclic-AMP response element-based signaling assays for characterization of Trk family tyrosine kinases modulators.

Neurotrophins (NTs) induce gene transcription by binding their high-affinity tropomyosin-related kinase (Trk) receptors and initiating intracellular signal transduction cascades. In particular, activation of the cyclic AMP response element (CRE) in the promoters of target genes serves as surrogate markers for Trk receptor activation as demonstrated in both in vivo and in vitro systems. We used a HEK293 cell line stably expressing a CRE-luciferase reporter gene to develop an assay for monitoring Trk activation in response to their cognate ligands. Using TrkB, we showed that the assay was sensitive to physiological concentrations of brain-derived neurotrophic factor (BDNF) and that the signal was sufficiently robust to be suitable for implementation in high-throughput format. Further characterization of the TrkB expressing stable cell lines showed high-affinity binding for BDNF, a high density of receptor expression, and supported BDNF-mediated phosphorylation signaling. Consistent with this, inhibitors of phosphatidylinositol 3-kinase and the phospholipase C-gamma pathways led to reduction of BDNF-mediated luciferase responses. In contrast, inhibitors of mitogen-activated protein kinase pathways further potentiated BDNF responses. This assay was NT-Trk receptor pair-selective and shown to be further applicable to other Trk family members. This assay may be useful in screening compound libraries to identify Trk agonists, which may be applied towards discriminating between the activities of the different Trk receptor family members and the development of pharmacological drugs.

Blotting, Western↗

PubMed2006

Effect of operating parameters and reactor structure on moderate temperature dry desulfurization.

A moderate temperature dry desulfurization process at 600-800 degrees C was studied in a pilot-scale circulating fluidized bed flue gas desulfurization (CFB-FGD) experimental facility. The desulfurization efficiency was investigated for various operating parameters, such as bed temperature, CO2 concentration, and solids concentration. In addition, structural improvements in key parts of the CFB-FGD system, i.e., the cyclone separator and the distributor, were made to improve the desulfurization efficiency and flow resistance. The experimental results show that the desulfurization efficiency increased rapidly with increasing temperature above 600 degrees C due to enhanced gas diffusion and the shift of the equilibrium for the carbonate reaction. The sorbent sulfated gradually after quick carbonation of the sorbent with a long particle residence time necessary to realize a high desulfurization ratio. A reduced solids concentration in the bed reduced the particle residence time and the desulfurization efficiency. A single-stage cyclone separator produced no improvement in the desulfurization efficiency compared with a two-stage cyclone separator. Compared with a wind cap distributor, a large hole distributor reduced the flow resistance which reduced the desulfurization efficiency due to the reduced bed pressure drop and worsened bed fluidization. The desulfurization efficiency can be improved by increasing the collection efficiency of fine particles to prolong their residence time and by improving the solids concentration distribution to increase the gas-solid contact surface area.

Air Pollution↗

PubMed2006

Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma.

Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the antitumor activity of the topoisomerase I inhibitor irinotecan (CPT-11), which is used to treat advanced colorectal carcinoma. Since PARP inhibitors sensitize tumor cells also to the methylating agent temozolomide (TMZ) and clinical trials are evaluating CPT-11 in combination with TMZ, we tested whether the PARP inhibitor GPI 15427 (10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one) increases the efficacy of CPT-11 + TMZ against colon cancer. Moreover, due to the ability of PARP inhibitors to avoid cell death consequent to PARP-1 overactivation, we evaluated whether oral administration of GPI 15427 provides protection from the dose-limiting intestinal toxicity of CPT-11. The results of colony formation assay indicated that GPI 15427 increased the antiproliferative effects (combination index <1) of TMZ + SN-38 (the active metabolite of CPT-11) against colon cancer cells. Accordingly, GPI 15427 (40 mg/kg/dayx5 days per os) in combination with TMZ (10 mg/kg/dayx5 days) + CPT-11 (4 mg/kg/dayx5 days) significantly reduced the growth of tumor xenografts. Oral administration of GPI 15427 (40 mg/kg/q2x3 days) prevented intestinal injury and diarrhea induced by CPT-11 (30 mg/kg/day x 3 days) reducing inflammation and PARP-1 overactivation, as evidenced by immunohistochemical staining of intestinal tissue with antipoly(ADP-ribose) antibody (Ab). In conclusion, the PARP inhibitor represents a novel strategy to enhance the antitumor efficacy and reduce toxicity of chemotherapy in colon cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Effects of midazolam on muscarinic receptor of brain in healthy and scopolamine-treated rats].

OBJECTIVE: To investigate the recent and permanent effects of pretreatment with midazolam on muscarinic receptor of brain in healthy and scopolamine-treated rats. METHODS: (1) In recent effect group, thirty-eight male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=10), midazolam+scopolamine group (Mid+sco, n=10). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco groups were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 4th, 5th, and 6th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while same voluminal physiological saline was administered in Con group and Mid group. (2) In permanent effect group, thirty-six male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=9), midazolam+scopolamine group (Mid+sco, n=9). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco group were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 10th, 11th, and 12th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while the same voluminal physiological saline was administered in Con group and Mid group. (3)Then the rats was decapitated and the cerebra cortex and hippocampus were removed. The binding capacity of muscarinic receptor with [3H] QNB were determined. Bmax and Kd of muscarinic receptor in hippocampus were determined by Scatchard analysis in recent effect group. RESULTS: (1) In recent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group, Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group (P<0.05) and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.01). Kd of muscarinic receptor in hippocampus in Sco group and Mid group were higher than in Con group and Mid+sco group (P<0.01). Bmax of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group (P<0.05), Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.05). There was no significant difference of the binding capacity of muscarinic receptor in cortex. (2) In permanent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group and Mid group than in Sco group and Mid+sco group (P<0.01). There was no significant difference of the binding capacity of muscarinic receptor in cortex. CONCLUSION: Pretreatment with intraperitoneal injection of 50 mg/kg midazolam for three days had no effect on muscarinic receptor of cortex, but could induce the binding capacity of muscarinic receptor with [3H] QNB and change the density and affinity of muscarinic receptor in hippocampus in healthy and scopolamine-treated rats, yet the changes were not permanent.

Animals↗