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81.
Gao CL Dean RC Pinto A Mooneyhan R Connelly RR McLeod DG Srivastava S Moul JW 《The Journal of urology》1999,161(4):1070-1076
82.
Faaij RA Srivastava N van Griensven JM Schoemaker RC Kluft C Burggraaf J Cohen AF 《European journal of clinical pharmacology》1999,54(12):929-935
Objective: Pentosan polysulphate sodium (PPS), a heparin-like drug, is supposed to be orally applicable. The objective of the present
study was to assess the oral bioavailability of PPS. However, since specific assays for PPS do not exist, this was done by
using primary and secondary effect parameters.
Methods: The study was carried out using a three-way randomized crossover design with 18 healthy young male volunteers. The subjects
received three treatments: PPS i.v. (50 mg), PPS orally (1500 mg) and placebo (orally). Blood sampling was done for activated
partial thromboplastin time (APTT), anti-Xa activity, hepatic triglyceride lipase, lipoprotein lipase, tissue plasminogen
activator (t-PA) activity, fibrin plate lysis, total triglyceride, total cholesterol, HDL and LDL.
Results: Intravenously administered PPS significantly increased APTT, anti-Xa activity, hepatic triglyceride lipase and lipoprotein
lipase compared with placebo in a magnitude comparable to other i.v. heparin-like compounds. Orally administered PPS did not
significantly influence any of the parameters when compared with placebo. Point estimates for the oral bioavailability of
PPS were in the range of 0% with small confidence intervals (CIs).
Conclusion: The oral bioavailability of PPS is negligible in young healthy males.
Received: 8 June 1998 / Accepted in revised form: 19 October 1998 相似文献
83.
Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT), which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes. 相似文献
84.
85.
E. D. Srivastava M. A. H. Russell C. Feyerabend J. G. Masterson J. Rhodes 《Psychopharmacology》1991,105(1):63-68
We studied the responses of smokers and life-long non-smokers to transdermal nicotine patches over 24 h in three groups of
subjects: non-smokers on a 15 mg patch (n=8), non-smokers on a 30 mg patch (n=8) and smokers on a 30 mg patch (n=8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations
of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD=3.7), 10.9 (SD=4.2)
and 4.1 (SD=2.7) ng/ml in the three groups, respectively (P<0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (
Cmax 13.9 ng/ml, SD=4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P<0.01) within the first hour, and seven dropped out (P<0.01) at 3–8 h due mainly to severe nausea, vomiting or headache (
Cmax 18.4 ng/ml, SD=4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (
Cmax 7.9 ng/ml, SD=3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether
this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires
replication. 相似文献
86.
In vitro binding of gibberellin A(4) to extracts of cucumber measured by using DEAE-cellulose filters 总被引:1,自引:0,他引:1
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Keith B Brown S Srivastava LM 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(5):1515-1519
A rapid method for assaying [3H]gibberellin A4 bound to a soluble protein from cucumber hypocotyls by using DEAE-cellulose filter discs is described. The binding is saturable, reversible with unlabeled gibberellin A4, and has a half-life of association under nonequilibrium conditions at 0-4°C of 6-7 min. By using this assay, the dissociation constant (Kd) was estimated to be 70 nM and the number of binding sites, 0.4 pmol mg-1 of soluble protein or 0.69 pmol g-1 (fresh weight) of hypocotyls. The speed and reliability of the assay make it invaluable for kinetic studies involving competitors. Thus, it has been possible to show that gibberellins that are biologically active in a cucumber bioassay compete for binding to the same protein and their calculated affinity constants bear a direct relationship to their known activities in the cucumber bioassay. Gibberellins that are inactive in this bioassay and other plant hormones, such as indoleacetic acid, abscisic acid, and kinetin, show a noncompetitive interaction. 相似文献
87.
B I Srivastava 《Cancer research》1976,36(5):1825-1830
All 5 thymus-dependent cell (T-cell) lines (Molt-3; Molt-4; RPMI-8402; CCRF-CEM; CCRF-HSB-2) and 7 thymus-independent cell (B-cell) lines (RPMI-8382, RPMI-8392, RPMI-8412, RPMI-8422, RPMI-8432, RPMI-8442, CCRF-SB) established so far from acute lymphoblastic leukemia patients were examined for deoxynucleotide polymerizing enzymes. All T- and B-cells had DNA polymerase gamma, DNA polymerase beta, and terminal deoxynucleotidyl transferase both in the soluble (the latter 2 enzymes only in small amounts) and chromatin fraction, whereas DNA polymerase alpha was found only in the soluble fraction. With respect to their sedimentation and chromatographic behavior, template-primer requirements, Km for deoxythymidine triphosphate or deoxyguanosine triphosphate divalent cation preference, effect of NaCI and inhibitors, the enzymes from T- and B-cells resembled each other and those from other mammalian cells. DNA polymerase alpha, beta, and gamma from T-cells like those from "fresh" acute lymphoblastic leukemia cells, were more thermolabile than those from B-cells or phytohemagglutinin-stimulated normal lymphocytes. In addition, the terminal deoxynucleotidyl transferase from the above cells was completely inactivated in 5 to 6 min at 50 degrees, whereas the DNA polymerase alpha, beta, and gamma retained considerable activity even after heating for 25 min at 50 degrees. DNA polymerase activity of the soluble fraction from T-cells was of the same magnitude as in B-cells when expressed on a DNA basis but twice that of B-cells when expressed on a protein basis. High terminal deoxynucleotidyl transferase activity, equivalent to that observed in acute lymphoblastic leukemia cells, was found in all T-cell lines that, when expressed on a DNA basis, was 30 to 100 times higher than the B-cell lines tested. These results support the suggestion of earlier investigators that T-cell lines examined here may have originated from leukemic cells. 相似文献
88.
Heidenreich B Heidenreich A Sesterhenn A Srivastava S Moul JW Sesterhenn IA 《European urology》2000,38(4):475-482
INTRODUCTION AND OBJECTIVES: The linked p16(INK4)/MTS1 and p15(INK4B)/MTS2 genes on chromosome 9p21 encode proteins that inhibit the cyclinD dependent kinases CDK4/6. Biallelic homozygous deletions involving this locus have been identified in a wide range of tumor cell lines, but in a lower frequency of primary tumors. As PCR based approaches analyzing for homozygous deletions could be confounded by unavoidable contributions of normal cells in microdissected tissue, we performed in situ hybridization (ISH) on primary prostate carcinomas to accurately evaluate p16 and p15 copy numbers on a cell-by-cell basis. MATERIAL AND METHODS: p16 and p15 loci were evaluated in 28 pT3N0M0 prostate cancer specimens. Of 28 patients, 15 (53%) were ascertained showing no recurrence (mean follow-up 61+/-17 months), 13 (47%) developed recurrences within 27+/-19 months. Tissues were provided for ISH analysis in a blinded fashion. Isolated DNA derived from P1 clone 1063 compromising p16 and p15 as well as a centromeric probe for chromosome 9 were used for hybridization. Signals were enumerated within 300 interphase nuclei per tumor specimen, and in 100 nuclei derived from 18 benign prostate tissues and 7 adjacent PIN regions. RESULTS: ISH detected aneuploid tumors in 12/13 (92%) patients with recurrence and in 5/15 (33%) without recurrence (p<0.0014). Whereas 3/7 PIN specimens associated with nonrecurrent PCA demonstrated euploidy, all 4/7 PIN associated with recurrent disease demonstrated the same aneuploidy for chr9 as the primary tumor. All benign tissues evaluated exhibited euploidy for chr9, p16 and p15. None of the PCA and PIN samples revealed homozygous deletions for p16(INK4)/MTS1/p15(INK4B)/MTS2; 2/28 (7.1%) PCA exhibited partial deletion for p16(INK4)/MTS1/p15(INK4B)/MTS2 and aneuploidy for chr9; both PCA derived from the recurrent group. CONCLUSIONS: Deletion of 9p21 was rare and therefore such genetic alterations may not play an important role in the pathogenesis of PCA. Analysis of the limited number of PCA examined suggest a strong association between chr9 aneuploidy and recurrenct disease. Aneuploidy in both PIN and PCA suggests that the clinical outcome of PCA might already be determined in the preinvasive PIN. 相似文献
89.
Preeti Sharma Subha Rastogi Sunita Bhatnagar Janmejya K. Srivastava Anuradha Dube Purushottam Y. Guru Dinesh K. Kulshrestha Bishan N. Mehrotra Bhola N. Dhawan 《Drug development research》2003,60(4):285-293
Tephrosia purpurea (family: Fabaceae), which is used in traditional remedies for the treatment of febrile attacks, enlargement and obstruction of liver, spleen, and kidney, was found to have significant antileishmanial activity, and has been extensively fractionated to locate the abode of activity. A fraction (F062) obtained from N‐butanol extract of T. purpurea showed consistent antileishmanial activity at 50 mg/ kg × 5 days by oral route against Leishmania donovani infection in hamsters. Activity was further confirmed in a secondary model, i.e., Indian langur monkeys (Presbytis entellus). Thus, the fraction F062 from this plant possesses potential to produce significant antileishmanial activity by oral route without producing any toxic side effects. Drug. Dev. Res. 60:285–293, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
90.
Development and Application of a Serum C-Telopeptide and Osteocalcin Assay to Measure Bone Turnover in an Ovariectomized Rat Model 总被引:2,自引:0,他引:2
Srivastava AK Bhattacharyya S Castillo G Wergedal J Mohan S Baylink DJ 《Calcified tissue international》2000,66(6):435-442
Biochemical markers applicable to the ovariectomized rat model can provide important tools for studying the bone remodeling
process in this animal model of postmenopausal osteoporosis. We describe the development and application of two biochemical
markers, a C-telopeptide (of type-I collagen) enzyme-linked immunosorbent assay (ELISA) for measuring bone resorption and
an osteocalcin radioimmunoassay (RIA) for measuring bone formation in rat serum. The C-telopeptide ELISA is based on an affinity
purified polyclonal antibody generated against human sequence DFSFLPQPPQEKAHDGGR. The antibody epitope involves amino acid
sequence, which is similar in rat and human carboxyl terminal peptide of type-I (alpha 1) collagen. Sensitivity of the ELISA
was 0.3 ng/ml. The averaged intra- and interassay variation was CV <7%. Averaged dilution and spiked recoveries were 91% and
105%, respectively. The second marker developed is a synthetic peptide-based osteocalcin RIA, which does not require isolation
and purification of intact osteocalcin from rat bone. Osteocalcin antiserum used in the RIA was generated in rabbits against
a synthetic peptide comprising amino acids 33–49 of the rat osteocalcin sequence. The sensitivity of the RIA was 0.15 ng/ml
of peptide. The averaged intra (n = 10) and interassay variations for two controls were CV <9% and 12%, respectively. The
averaged dilution and spiked recoveries were 99.6%. In vivo validation of the C-telopeptide ELISA and osteocalcin RIA was performed in an ovariectomized (OVX) rat model. In 12-week-old
OVX Sprague Dawley rats, the C-telopeptide and osteocalcin concentrations were approximately 65% and 40%, respectively, higher
than the sham group. Estradiol repletion significantly lowered the C-telopeptide and osteocalcin concentration to the levels
of the sham group. In addition, changes in serum C-telopeptide concentration correlated negatively with trabecular BMD measured
by pQCT (r =−0.51, P < 0.001). In conclusion, the C-telopeptide ELISA and osteocalcin RIA exhibited required sensitivity, accuracy, and adequate
discriminatory power to be used for measuring bone resorption and bone formation in the ovariectomized rat model.
Received: 20 August 1999 / Accepted: 5 January 2000 相似文献