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Phosphonate esters were synthesized and investigated by positive ion electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). It was found that for the sodiated adduct there were two novel rearrangement reactions, in which the phosphoryl oxygen atom migrated to the carbonyl carbon and a cleavage occurred at the amide bond, or a benzylamine fragment was lost and the phosphorus was reduced. However, when the methyl group substituted for the isopropyl group, these migrations were inhibited. A possible mechanism was proposed, and high-resolution mass spectrometry was applied to identify the formula of these novel ions. These results showed that ESI-MS is a useful tool for the structural determination of phosphonate esters., (Copyright 2007 John Wiley & Sons, Ltd.)

Reactions of 1,4,7-triazacyclononane-1,4,7-triyl-tris(methylenephosphonic acid) [notpH(6), C(9)H(18)N(3)(PO(3)H(2))3] with different lanthanide salts result in four types of Ln-notp compounds: [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(NO(3))(H(2)O)].4H2O (1), [Ln = Eu (1 Eu), Gd (1 Gd), Tb (1 Tb)], [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]Cl.3H2O (2) [Ln = Eu (2 Eu), Gd (2 Gd), Tb (2 Tb)], [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]ClO4.8H2O, (3) [Ln = Eu (3 Eu), Gd (3 Gd)], and [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]ClO4.3H2O (4), [Ln = Gd (4 Gd), Tb (4 Tb)]. Compounds within each type are isostructural. In compounds 1, dimers of {Ln2(notpH4)2(NO3)2(H2O)2} are found, in which the two lanthanide atoms are connected by two pairs of O-P-O and one pair of mu-O bridges. The NO3- ion serves as a bidentate terminal ligand. Compounds 2 contain similar dimeric units of {Ln2(notpH4)2(H2O)2} that are further connected by a pair of O-P-O bridges into an alternating chain. The Cl- ions are involved in the interchain hydrogen-bonding networks. A similar chain structure is also found in compounds 3; in this case, however, the chains are linked by ClO4- counterions through hydrogen-bonding interactions, forming an undulating layer in the (011) plane. These layers are fused through hydrogen-bonding interactions, leading to a three-dimensional supramolecular network with large channels in the [100] direction. Compounds 4 show an interesting brick-wall-like layer structure in which the neighboring lanthanide atoms are connected by a pair of O-P-O bridges. The ClO4- counterions and the lattice water molecules are between the layers. In all compounds the triazamacrocyclic nitrogen atoms are not coordinated to the Ln(III) ions. The anions and the pH are believed to play key roles in directing the formation of a particular structure. The fluorescence spectroscopic properties of the Eu and Tb compounds, magnetic properties of the Gd compounds, and the catalytic properties of 4 Gd were also studied.

Nine typical phytoplankton species were chosen and cultivated under two temperatures (20 and 15 degrees C) and two illumi- nations (7000 and 1100 lux), and their absorption spectra at different growth period were measured. Firstly, singular value decomposition was used on the matrix, which is composed of the autoscaled spectra data. The S1/msigma(i=1)Si was used to compare the similarities of spectra. Twenty-five representative spectra were obtained for the nine species of phytoplankton. Among them, there are one spectrum for each of Isochrysis galbana and Chaetoceros Debilis, two for each of Platymonas helgolanidica and Chaetoceros curvisetus, three for Gymnodinium sp., and four for each of Alexandrium tamarense, Prorocentrum dentatum, Skeletonema costatuma and Synechococcus sp. Then, feature extraction was processed to obtain the characteristic spectra, including seven incontinuous wavelengths that have great ability to differentiate species. They are 340. 5-420. 5 nm, 423. 5-431 nm, 440.5-525.5 nm, 760.5, 763.5, 769.5 and 856.5 nm. Consequently, they form characteristic spectra. The discriminant result is 80%.

The present study investigates the roles of the spinal phosphoinositide 3-kinase (PI3K) signaling pathway in naloxone-precipitated withdrawal in acute and chronic morphine-dependent mice. There are two principal findings: (1) intrathecal pretreatment with wortmannin or LY294002, two structurally unrelated PI3K inhibitors, produced a dose-dependent increase of naloxone-precipitated withdrawal jumping, which was accompanied by an increased expression of spinal Fos protein in acute and chronic morphine-dependent mice; and (2) the expression of spinal p110gamma, the catalytic subunit PI3K, in the membrane fraction was significantly down-regulated by naloxone-precipitated withdrawal in acute and chronic morphine-dependent mice. This study provides new evidence showing that inactivation of the PI3K signaling pathway in the spinal cord may be involved in the expression of morphine withdrawal.

The growth-inhibiting effects of Gemini1231 surfactant on Prorocentrum donghaiense, Alexandrium tamarense, Gymnodinium sp., Heterosigma akashiwo, Skeletonema costatum , Platymonas helgolanidica and Platymonas subcordiforus were investigated. The results demonstrate that the growth of P. donghaiense, A. tamarense and H. akashiwo was strongly inhibited in medium containing Gemini1231 from 0.2 to 0.5 mg x L(-1), and the S. costatum was also inhibited at concentrations above 0.5 mg x L(-1). However, the effects of this surfactant on the growth of Gymnodinium sp. and two beneficial green microalgae tested were negligible under the same treatment, indicating the potential for the selective control of red tide organisms. In addition, the analysis of the correlation between the inhibitory effect of the Gemini1231 on the algae tested and fatty acid composition of the algae implied that the differences in the fatty acid composition, especially the proportion of PUFAs, were responsible for the species-specific responses to biquaternary ammonium salt.

The discrimination of phytoplankton classes using the characteristic fluorescence spectra extracted from three-dimensional fluorescence spectra was investigated. Single species cultures of 11 phytoplankton species, representing 5 major phytoplankton divisions, were used. The 3D fluorescence spectra of the cultures grown at different temperatures (20 and 15 degrees C) and illumination intensities (140, 80 and 30 microM m(-2) s(-1)) were measured and their feature extraction methods were explored. Ordering Rayleigh and Raman scattering data as zero, the obtained excitation-emission matrices were processed by both singular value decomposition (SVD) and trilinear decomposition methods. The resulting first principal component can be regarded as the characteristic spectrum of the original 3D fluorescence spectrum. The analysis shows that such characteristic spectra have a discriminatory capability. At different temperatures, the characteristic spectra of Isochrysis galbana, Platymonas helgolanidica and Skeletonema costatuma have high degrees of similarity to their own species samples, while the spectra similarities of Alexandrium tamarense, Prorocentrum dentatum, Pseudo-nitzschia pungens, Chaetoceros curvisetus, Ch. Debilis, Ch. Didymus and Synechococcus sp. are not as significant as the other three species. C. curvisetus, Ch. Debilis and Ch. Didymus, belonging to genus Chaetoceros, have identical spectra and cannot be discriminated at all. Regarding all six diatom species as one class, the average discriminant error rate is below 9%. It is worth mentioning that the diatom class can be distinguished from A. tamarense and P. dentatum, which belong to Dinophyta.

The purified terephthalic acid (PTA) petrochemical wastewater molecular toxicity detected by use of Mouse Genome 430A 2.0 GeneChip was conducted in this research. The toxic dose to male mice was 0.03 g/(kg x d) of PTA in the wastewater. The mice liver total RNA was isolated as the temple for synthesis of cDNA and then the cDNA as the temple for synthesis of cRNA. Hybridizing the cRNA with the target genes on the gene chip, there were 232 genes expression levels up-regulated and 74 genes down-regulated discovered obviously. The foremost 40 genes for both the highest and the lowest expression levels involved endogenetic steroid and hormone metabolism, immune system, the leukocyte activity and inflammation, detoxification in liver, reproduction and growth hormone, regulation immune factors of anti-tumor and anti-infection and cancer to the mice sampled. The data suggest the PTA wastewater contained over 5 aromatics and their toxicities integrated were much higher than the pure chemical PTA. And the pure chemical PTA toxicities data cannot be used to evaluate the toxicity of the PTA wastewater instead.

A new complex [Cu (Thr)(Phen)H2O] SO4 . HO2 x CH3 OH (Thr = DL-Threonine, Phen = o-Phenanthroline), which has not been published, was synthesized and characterized by elemental analysis, IR spectroscopy, and TG-DTA. The interaction of the complex and sperm DNA was studied by electronic absorption and ethidium bromide (EB) fluorescence spectroscopy. The result indicates that the maximal absorption peaks of this complex are red-shifted and the intensity is weakened; At the same time, it can to some extent quench the emission intensity of EB-DNA system. Therefore, the authors come to a conclusion that the interaction of this complex and sperm DNA is intercalation.

We obtain synchronized 45-fs and 0.848-ps pulses by achieving cross-mode locking in a double-cavity dual-wavelength femtosecond Ti:sapphire laser. Autocorrelation and cross correlation show that the femtosecond and picosecond pulses are well synchronized, with a timing jitter of 41 fs. Cross-phase modulation dominates the processes of cross-mode locking and synchronization.

The biodegradation and toxicity of the purified terephthalic acid (PTA) processing wastewater was researched at NJYZ pilot with the fusant strain Fhhh in the carrier activated sludge process (CASP). Sludge loading rate (SLR) for Fhhh to COD of the wastewater was 1.09 d(-1) and to PTA in the wastewater was 0.29 d(-1). The results of bioassay at the pilot and calculation with software Ebis3 showed that the 48h-LC50 (median lethal concentration) to Daphnia magna for the PTA concentration in the wastewater was only 1/10 of that for the chemical PTA. There were 5 kinds of benzoate pollutants and their toxicities existing in the wastewater at least. The toxicity parameter value of the pure chemical PTA cannot be used to predicate the PTA wastewater toxicity. The toxicity of the NJYZ PTA wastewater will be discussed in detail in this paper.

In the pilot study of treating the purified terephthalic acid (PTA) wastewater with the functional Strain Fhhh in the carrier activated sludge process (CASP), the ratio of COD: TN: TP and the concentrations of Cu, Mn, Se and Zn were controlled to improve the manganese peroxidase (MnP) levels for increasing the treatment efficiency. When the ratio of COD: TN: TP was 100: 0.36: 0.15 and the concentrations of Cu, Mn, Se and Zn were 0.54, 5.07, 0.00 and 0.08 mg/L, the MnP specific activity (MnP-SA) reached 689 U/L, and the sludge loading rate to COD(SLRC) was 1.09 d(-l), which was 4--7 fold of that in other processes reported. The data indicated that improving MnP level could enhance the degradability of Fhhh. And the potentials of Fhhh and CASP will be also discussed in this paper.

The effectiveness for the XZEH medicine wastewater treatment biotechnology was conducted. The results show that it needs to increase 28% of the aeration tank volume in order to meet the effluent COD concentration at the first grade wastewater discharge standard level in China. If the engineered strain Xhhh and informatics software (Ebis) were used, the specific degradation rate of Xhhh strain may be higher 128% than that of the natural bacterium XZ strain and the aeration tank needed may be 51% decreased. This should be a potential technical patch for improving the biotechnological effectiveness and making the effluent at the first grade discharge standard.

Aims: The aim of this study is to investigate whether angiotensin-converting enzyme inhibitor (ACEI) therapy with ramipril could augment circulating endothelial progenitor cells (EPCs) with enhanced functional activity in patients with stable coronary artery diseases., Methods and Results: 20 patients with angiographically documented stable coronary artery disease (CAD) were prospectively treated with 5 mg of ramipril per day for 4 weeks. Before and weekly after the initiation of ramipril therapy, EPCs were isolated from peripheral blood and counted. Ramipril treatment of patients with stable CAD was associated with an approximately 1.5-fold increase in the number of circulating EPCs by 1 week after initiation of treatment; this was followed by sustained increased levels to approximately 2.5-fold throughout the 4-week study period. In addition, ramipril treatmen was associated with increases in the functional activity of EPCs, as assessed by their proliferation, migration, adhesion and in vitro vasculogenesis capacity., Conclusion: The results of the present study define a novel mechanism of action of ACEI treatment in patients with stable CAD: the augmentation of circulating EPCs with enhanced functional activity. Given the well-established role of EPCs of participating in repair after ischemic injury, stimulation of EPCs by ACEI may contribute to the clinical benefit of ACEI therapy in patients with CAD.

Current treatment of malignant glioma brain tumors is unsatisfactory. Gene therapy has much promise, but target-specific vectors are needed. Endothelial progenitor cells (EPCs) have in vivo homing specificity to angiogenic sites and are thus potential vehicles for site-specific gene therapy. However, reports of EPCs "homing" to intracranial solid tumors are lacking. We investigated EPCs' "homing" specificity using a murine intracranial glioma model. EPCs, derived from human cord blood, were labeled with a fluorogenic agent CFSE and intravenously injected into SCID mice bearing orthotopic gliomas. At 7-14 days after EPC injection, mouse brains and other vital organs were examined for distribution of transplanted EPCs. As controls, CFSE-labeled human umbilical vein endothelial cells (HUVECs) and EPCs were intravenously injected into matched glioma SCID mice (HUVEC control groups) and nontumor SCID mice (nontumor-bearing control groups), respectively. Fluorescence image analysis revealed that systemically transplanted EPCs 'homed' to brain tumors with significantly higher specificity as compared to other organs within the experimental group (P<0.001) and to anatomically matched brain sections from the control groups (P<0.001). Our study demonstrates EPCs' in vivo tropism for intracranial gliomas, with potential for cell delivery of brain tumor spatial-specific gene therapy.

A "cW (pollutant concentration in water) Balance Method" was proposed, and the kinetic parameters for bioconcentration of No. 0 diesel water-accommodated fraction by phytoplankton was measured and calculated by a modified bioconcentration model with non-linear fitting software. The data and parameters obtained by "cW Balance Method" showed well correlationship with those by the extraction of ultrasonication bath with the equilibrium method. The technique proposed in the present study is particularly well suited for the study on the bioconcentration of organic pollution toxins in the field for its convenience, simplicity, veracity and reliability.

Aim: To investigate effects of (-), (+)-7-hydroxy-clausenamide (7-OH-Clau) on basal synaptic transmission in the dentate gyrus of anesthetized rats., Methods: Extracellular recording of the population spike (PS) of hippocampal dentate gyrus following application of low-frequency stimulation (1/30 Hz, 1.0 mA)., Results: Fifteen, thirty and sixty minutes after intracerebroventricular (icv) administration of an estimated final brain concentration of 2 x 10(-6) mol.L-1, (-)-7-OH-Clau caused over 30% increase relative to basal PS amplitude before administration, and 27%-41% increase relative to vehicle control (P < 0.05), while (+)-7-OH-Clau exhibited 18%-25% and 11%-20% decrease in the PS amplitude when compared with basal PS amplitude and vehicle control (P < 0.05), respectively., Conclusion: The basal synaptic transmission in the dentate gyrus of the rat hippocampus can be potentiated by (-)-7-OH-Clau and attenuated by (+)-7-OH-Clau, indicating that there was a stereoselective difference between the two enantiomers in the modulation of synaptic responses and plasticity.

Objective: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft., Methods: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E1), experimental group 2 (group E2), and experimental group 3 (group E3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E1: 5-minute ischemia and 10-minute reperfusion; Group E2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-alpha and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion., Results: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-alpha in the experimental groups E1, E2, and E3 were significantly lower than in the control group (P<0.05), and the levels in group E2 were significantly lower than in groups E1 and E3 (P<0.05). At 24 hours, the levels of TNF-alpha in group E2 were significantly lower than in groups C, E1 and E3 (P<0.05). At 2 and 6 hours, apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05). Apoptosis index in group E2 was significantly less than groups E1 and E3 (P<0.05). At 24 hours apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05)., Conclusions: Ischemic preconditioning could attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-alpha. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a better way to protect liver graft from ischemia-reperfusion injury.

Bcl-2 is a key antiapoptotic protein, and it confers survival advantages on many types of tumors by inhibiting apoptotic cell death. Malignant gliomas are the most common primary central nervous system tumors, but the role of bcl-2 in these tumors has not been defined. We investigated the impact of bcl-2 on malignant gliomas by suppressing its expression. Antisense human bcl-2 cDNA was transfected into human malignant glioma cells. The effects of bcl-2 protein down-regulation on glioma cell morphology, in vitro tumor growth, and tumorigenicity in nude mice, as well as chemosensitivity to cisplatin, were studied. Expression of antisense bcl-2 cDNA decreased bcl-2 protein by more than sixfold. Antisense bcl-2 stable transfectants (AS-bcl-2) showed profound morphological change and markedly retarded cell growth in vitro. Transplantation of AS-bcl-2 cells resulted in no tumor formation, whereas backbone plasmid transfectant control formed tumors in each mouse transplanted. Expression of antisense bcl-2 in glioma cells resulted in significantly increased cytotoxicity of cisplatin. In conclusion, antisense bcl-2 expression can effectively reduce glioma survival, including retarding in vitro growth, complete loss of tumorigenicity, and significantly enhanced cisplatin cytotoxicity. These results suggest that bcl-2 plays an important role in glioma malignancy and chemoresistance. Development of strategies targeted at bcl-2 has the potential to advance treatment for malignant gliomas., (Copyright 2003 Wiley-Liss, Inc.)

The pharmacokinetics of clausenamide (CLA) enantiomers and their metabolites were investigated in Wistar rat. After intravenous and oral administration at a dose of 80 and 160 mg/kg each enantiomer, plasma concentrations of (-)- or (+)-CLA and its major metabolites were simultaneously determined by reverse-phase HPLC with UV detection. Notably, stereoselective differences in pharmacokinetics were found. The mean plasma levels of (+)-CLA were higher at almost all time points than those of (-)-CLA. (+)-CLA also exhibited greater t(max), C(max), t(1/2beta), AUC(0-12h), and AUC(0--> infinity) and smaller CL (or CL/F) and V(d) (or V(d)/F), than its antipode. The (+)/(-) isomer ratios for t(1/2beta), t(max), AUC(0-12 h), and AUC(0--> infinity), which ranged from 1.26 to 2.08. The ratio for CL (or CL/F) was about 0.5, and there were significant differences in these values between CLA enantiomers (P < 0.05), implying that the absorption, distribution, and elimination of (-)-CLA were more rapid than those of (+)-CLA. Similar findings for (-)-7-OH-CLA, the major metabolite of (-)-CLA, and (+)-4-OH-CLA, the major metabolite of (+)-CLA, can be also seen in rat plasma. The contributing factors for the differences in stereoselective pharmacokinetics of CLA enantiomers appeared to be involved in their different plasma protein binding, first-pass metabolism and interaction with CYP enzymes, especially with their metabolizing enzyme CYP 3A isoforms., (Copyright 2003 Wiley-Liss, Inc.)

Aim: To investigate the enzyme kinetics of (-)3S,4R,5R,6S-clausenamide[(-)-Clau] and (+)-3R,4S,5S,6R-clausenamide[(+)-Clau] catalyzed by rat liver microsomes and compare their stereoselective differences., Methods: An in vitro metabolic system was built by using rat liver microsomes and NADPH-generating system. Clau and its metabolites were determined simultaneously by a reversed-phase high performance liquid chromatography. The kinetic parameters, K(m), Vmax, and metabolic rate, Vmax/K(m), were calculated by Eadie-Hofstee plot., Results: In the metabolic system, (-)-Clau was found to be mainly metabolized to 7-hydroxy-, 5-hydoxy- and 4-hydroxy-Clau, and 7-hydroxylation was a preferential pathway which exhibited higher Vmax/K(m) value (0.135 microL.min-1.mg-1) than those of 5- and 4-hydroxylation (0.063 and 0.068 microL.min-1.mg-1, respectively). For (+)-Clau, it was mainly metabolized to 4-hydroxy-Clau, whereas 7-hydroxy- and 4-hydroxy-Clau were so small that they could not be detected systematically. 4-Hydroxylation of (+)-Clau showed highest Vmam/K(m) value (0.547 microL.min-1.mg-1) among all the metabolites tested, which was 8.0 times higher than that of 4-hydroxylation of its antipode., Conclusion: The data indicated that there were obvious substrate stereoselective differences in the hydroxylation metabolism of (+)- and (-)-Clau, which provided an explanation of the difference of pharmacokinetic characteristics of Clau enantiomers in rats.

To identify which cytochrome P450 (CYP) isoform(s) are responsible for the metabolism of clausenamide (CLA) enantiomers in rats, effects of various CYP isoform inducers and inhibitors on the formation of CLA metabolites were investigated in liver microsomes. In incubations with rat liver microsomes, CLA enantiomers were mainly converted to 4-hydroxy, 5-hydroxy, and 7-hydroxy-metabolites. 4-OH-CLA was the major metabolite of (+)-3R, 4S, 5S, 6R-CLA [(+)-CLA], while 7-OH-CLA was the major one of (-)-3S, 4R, 5R, 6S-CLA [(-)-CLA]. In induction studies, enzymatic parameters were used to assess the role of different CYP forms in CLA hydroxylation reactions. A marked increase in the rate of metabolism of CLA enantiomers was observed in microsomes of dexamethasone treated rats, V(max)/K(m) values for 4-OH-(+)-CLA, 7-OH-, 5-OH-, and 4-OH-(-)-CLA were 5.3, 6.5, 3.0, and 5.9 times higher than those in control microsomes, respectively. Rifampicin treatment caused corresponding 1.7-, 2.6-, 3.1-, and 2.8-fold increases. Dex and Rif also increased in the amount of (+)-5- and (+)-7-OH-CLA that were not detectable in the control group. These results suggested that inducible CYP3A1 was involved in the hydroxylation of CLA enantiomers. In inhibition studies, ketoconazone (6.25 microM) completely inhibited the production of main metabolites of (-)-CLA (100%) and (+)-CLA (97%). Triacetyloleandomycin (12.5 microM) strongly inhibited the corresponding metabolites by 34-85%. These findings also indicated that institutive CYP3A2 shared a major role in the hydroxylation of CLA enantiomers with CYP3A1 in untreated rats. Together, the data suggested that CYP3A was the predominant isoform responsible for the metabolism of CLA enantiomers., (Copyright 2003 Wiley-Liss, Inc.)

In this paper, combustion characterization of pyrotechnic composition is investigated using a remote sensing Fourier transform infrared spectrometry. The emission spectra have been recorded between 4,700 and 740 cm-1 with a spectral resolution of 4 cm-1. The combustion temperature can be determined remotely from spectral line intensity distribution of the fine structure of the emission fundamental band of gaseous products such as HF. The relationship between combustion temperature and combustion time has been given. Results show that there is a violent mutative temperature field with bigger temperature gradient near combustion surface. It reveals that the method of temperature measurement using remote sensing FTIR for flame temperature of unstable, violent and short time combustion on real time is a rapid, accurate and sensitive technique without interference the flame temperature field. Potential prospects of temperature measurement, gas product concentration measurement and combustion mechanism are also revealed.

Access to each C=C face of adamantylideneadamantane (AA) and sesquihomoadamantene (SA) is hindered by the hydrogenic canopy consisting of four beta-hydrogens; otherwise, these olefins have quite normal environments. X-ray crystallography and density functional (DFT) calculations show a 0.5 A larger annular opening in the protective cover of AA than that in SA. This contributes to the remarkable differences in reactivity toward various reagents, not only by limiting access to the olefin site in SA but also by inhibiting reactions which force these hydrogens closer together. Thus, AA is subject to typical olefin-addition reactions with bromine, sulfuryl chloride, m-chloroperbenzoic acid, dioxygen, and so forth, albeit sometimes at attenuated rates. On the other hand, SA is singularly unreactive under identical reaction conditions, except for the notable exceptions that include Brønsted (protonic) acids, a nitrosonium cation, and dichlorine. The exceptions are characterized as three sterically limited (electrophilic) reagents whose unique reactivity patterns are shown to be strongly influenced by steric access to the C=C center. As such, the different degrees of steric encumbrance in the isomeric donors AA and SA shed considerable light on the diverse nature of olefinic reactions. In particular, they evoke mechanistic features in electrophilic addition versus electron transfer, which are otherwise not readily discernible with other less hindered olefinic donors. Transient structures of the olefinic-reaction intermediates such as the protonated carbocations AA-H+ and SA-H+ as well as the cation radicals AA*+ and SA*+ are probed by the combination of X-ray crystallographic analyses and density functional theoretical computations.

Subjects, Material and Methods: According to a randomized two-period crossover design, 12 Chinese male volunteers were treated with 2 sertraline tablet formulations, one was made in China as test tablet, the other was made in England as reference tablet. Each volunteer received each sertraline in a single dose of 150 mg. The 2 medications were carried out by a wash-out phase of 23 days. Blood samples were obtained just before dosing and at 10 time points until 96 hours after administration, and plasma sertraline concentrations were determined by a sensitive gas-chromagraphy electron-capture method with a lower limit of quantification of 0.625 ng/ml. The bioequivalence of 2 formulations was evaluated by the shortest 90% confidence interval method which corresponds to the two one-sided test method., Results: The point estimate (90% confidence interval) of the mean ratio (test/reference) for AUC(0-96) was 97.19% (82.66% to 122.33%), for Cmax 96.27% (83.64% to 121.36%), and for t(l/2) 96.31% (85.43% to 119.57%). Regarding Tmax (test-reference), the 90% confidence interval ranged from -4 to +4 hours, but the difference between the Tmax values of 2 products is clinically of minor importance., Conclusion: Therefore, it can be concluded that 2 sertraline tablet formulations are bioequivalent. administration, sertraline is slowly absorbed with peak plasma concentrations at 6 - 8 h, and has a terminal elimination half-life of approximately 26 h, indicating once-daily dosing is available. Clinically, it can be taken either in the morning or in the evening, with or without food [Ronfeld et al. 1997b]. In addition, it also exhibits higher plasma protein binding up to 97% and extensive first-pass metabolism. By demethylation, sertraline is metabolized primarily to N-demethylsertraline, and then eliminated by hydroxylation arid conjugation [Tremaine et al. 1989]. This study aimed at assessing of bioequivalence of two sertraline formulations (produced in China and England, respectively) in healthy male volunteers after a single dose administration.

Aim: To develop a method for measurement of biological activity of recombinant DNA-derived somatotropin (rhGH)., Methods: The effects of varying the route, frequency and period of administration of GH, the sex of test animals on the biological responses, body weight gain (BWG), and tibial epiphyseal width (TEW), of hypophysectomized (Hypox) rats were compared, respectively. 4-d BWG, 6-d BWG, and 6-d TEW tests were carried out simultaneously in the same group of Hypox rats to determine the biopotency of GH preparations according to a parallel line bioassay (6-point assay). The final result was chosen from the test which had smaller values for the index of precision (lambda) and the average rate of fiducial limits (ARFL) than other tests., Results: No significant differences in the responses between male and female rats, between sc and im, once daily and twice daily injections of bGH were found. But the BWG and TEW of Hypox rats injected with 0.045 and 0.135 IU.d-1 of bGH for 6 d were significantly greater than that for 4 d. Both 4-d BWG test and 6-d BWG test in the range from 0.020 to 0.500 IU.d-1 had values for lambda = 0.0660 and 0.1747, and for r = 0.9000 and 0.9237, respectively. Three estimates of rhGH preparation compared with the International Standard for somatotropin (IShGH), 4.6132, 3.9829, and 4.8023 IU/ampoule, were obtained separately from 4-d BWG test, 6-d BWG test and 6-d TEW test. And the result from 6-d BWG test was reported finally because it had smaller values for lambda and ARFL (0.0608 and 37.907%) than other two tests., Conclusion: Both BWG test and TEW test can be carried out simultaneously in the same group of Hypox rats. 6-d BWG test seemed to be more suitable for potency determination of GH preparations than 4-d BWG test and 6-d TEW test.

Seventeen tracheotomy patients were given gentamicin (Gen) into trachea at the dosage of 2 and 4 mg.kg-1. Gen concentration in serum was determined by fluorescence polarization immunoassay. Pharmacokinetic parameters were calculated by micro-computer pharmacokinetic program (MCPKP). T1/2Ka, Tp, and Cmax were 0.6 +/- 0.3 h, 1.7 +/- 0.7 h, and 4.6 +/- 1.8 micrograms.ml-1, respectively in 4 mg.kg-1 group and 0.3 +/- 0.3 h, 0.9 +/- 0.5 h, and 0.4 +/- 0.2 microgram.ml-1, respectively in 2 mg.kg-1 group (P < 0.05). T1/2Kel was 30 +/- 11 h in patients of serum creatine (Cr) > 2 mg% and 6 +/- 5 h in patients of Cr < 2 mg% (P < 0.01). No significant difference could be found between Cmax of different renal function patients (P > 0.05).

Seventeen patients after renal transplantation were infused iv cyclosporin A (CsA) 0.65 +/- 0.13 mg.kg-1.h-1. Blood CsA was determined by fluorescence polarization immunoassay (FPIA). Pharmacokinetic parameters were calculated from micro-computer pharmacokinetic programme T1/2 beta = 8.6 +/- 3.4 h, Vd = 3.2 +/- 1.3 L.kg-1. No significant difference was found between sexes and between age groups.