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1.
Summary The antimitotic activity of nimbidin, a drug from the plantMelia azadirecta indica, was assessed by its effect on the meristematic cells of onion root tips. The effect was almost similar to those of colchicine and vinca alkaloids. Recovery trials showed that the drug induces lethal damage in a considerable proportion of treated cells and may hence have applications in cancer chemotherapy. 相似文献
2.
Molecular determinants of antimalarial drug resistance are useful and informative tools that complement phenotypic assays
for drug resistance. They also guide the design of strategies to circumvent such resistance once it has reached levels of
clinical significance. Established resistance to arylaminoalcohols such as mefloquine and lumefantrine in SE Asia is mediated
primarily by gene amplification of the P. falciparum drug transporter, pfmdr1. Single nucleotide polymorphisms in pfmdr1, whether assessed in field isolates or transfection experiments, are associated with changes in IC50 values (to arylaminoalcohols and chloroquine), but not of such magnitude as to influence clinical treatment outcomes. Recently
described emerging in vitro resistance to artemisinins in certain areas correlates with mutations in the SERCA-like sequence PfATP6 and supports PfATP6 as a key target for artemisinins.
Received 13 February 2006; revised after revision 7 March 2006; accepted 29 March 2006 相似文献
3.
Summary The strainT. foetus KV 1/M 100, a sub-strain ofT. foetus Kv 1, was made highly resistant to metronidazole by several passages in mice under increasing drug pressure. This drug resistance was accompained by a remarkable cross-resistance to all 5-nitroimidazole-derivatives tested in vitro and in vivo. 相似文献
4.
Bromelain: biochemistry, pharmacology and medical use 总被引:10,自引:0,他引:10
Maurer HR 《Cellular and molecular life sciences : CMLS》2001,58(9):1234-1245
Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases,
demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active
factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and
lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical
drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation,
angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs,
particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic
activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological
studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator
by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of
distinct cytokines such as tumor necrosis factor-α, interleukin (Il)-1β, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially
promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet
aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not
depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential
to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits
platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further
clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time.
Received 25 August 2000; received after revision 29 March 2001; accepted 30 March 2001 相似文献
5.
The bacterial LexA transcriptional repressor 总被引:2,自引:0,他引:2
Bacteria respond to DNA damage by mounting a coordinated cellular response, governed by the RecA and LexA proteins. In Escherichia coli, RecA stimulates cleavage of the LexA repressor, inducing more than 40 genes that comprise the SOS global regulatory network.
The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation. In some
well-characterised pathogens, induction of the SOS response modulates the evolution and dissemination of drug resistance,
as well as synthesis, secretion and dissemination of the virulence. In this review, we discuss the structure of LexA protein,
particularly with respect to distinct conformations that enable repression of SOS genes via specific DNA binding or repressor
cleavage during the response to DNA damage. These may provide new starting points in the battle against the emergence of bacterial
pathogens and the spread of drug resistance among them. 相似文献
6.
Increasing evidence implies altered signaling through the neurotrophic receptor tyrosine kinase TrkB in promoting tumor formation
and metastasis. TrkB, sometimes in conjunction with its primary ligand BDNF, is often overexpressed in a variety of human
cancers, ranging from neuroblastomas to pancreatic ductal adenocarcinomas, in which it may allow tumor expansion and contribute
to resistance to anti-tumor agents. In vitro, TrkB acts as a potent suppressor of anoikis (detachment-induced apoptosis), which is associated with the acquisition of
an aggressive tumorigenic and metastatic phenotype in vivo. In view of its predicted contribution to tumorigenicity and metastasis in humans, TrkB corresponds to a potential drug target,
and preclinical models have already been established. The encouraging results of pharmacological Trk inhibitors in tumor xenograft
models suggest that TrkB inhibition may represent a promising novel anti-tumor therapeutic strategy. This hypothesis is currently
being evaluated in clinical trials. Here, we will discuss the latest developments on TrkB in these contexts as well as highlight
some critical questions that remain to be addressed for evaluating TrkB as a therapeutic target in cancer.
Received 12 October 2005; received after revision 19 December 2005; accepted 11 January 2006 相似文献
7.
D. Stürchler 《Cellular and molecular life sciences : CMLS》1984,40(12):1357-1362
Summary Malaria prevention is a main challenge for physicians, nurses, health officers and tour operators. The attack rate of malaria in travellers is 1–10/10,000 departures, and the case fatality rate of imported malaria is around 0.5/100. Travellers should be informed about the risk they are going to take, how to protect against mosquito bites, about the antimalarials they will have to take and about what to do when a malaria breakthrough should occur.The 4-aminoquinolines (chloroquine, amodiaquine) remain the drug of choice for the prevention ofPlasmodium vivax and of sensitiveP. falciparum infections. The problem is to find an effective and safe drug combination for travellers to areas whereP. falciparum is either resistant to chloroquine, to Fansidar (the combination of pyrimethamine plus sulfadoxine) or to both. These travellers will probably best be protected by an individually tailored drug combination, which includes amodiaquine or mefloquine as baseline drugs, and a supplementation with Fansidar, Maloprim (the combination of pyrimethamine with dapsone), paludrine or an antibiotic. 相似文献
8.
The present study identified aloe-emodin (AE, a hydroxyanthraquinone from Aloe vera and other plants) as a new anti-angiogenic compound with inhibitory effects in an in vivo angiogenesis assay and evaluates its effects on specific key steps of the angiogenic process. AE inhibits endothelial cell
proliferation, but this effect is not cell specific, since AE also inhibits tumor cell proliferation. Cell migration and invasion
are not remarkably affected by AE. On the other hand, AE has different effects on endothelial and tumor cell gelatinases.
Two main targets of the pharmacological action of AE as an anti-angiogenic compound seem to be urokinase secretion and tubule
formation of endothelial cells. Finally, AE produces a remarkable photocytotoxic effect on tumor cells. Taken together, our
data indicate that AE can behave both as an anti-tumor and an anti-angiogenic compound and suggest that AE could be a candidate
drug for photodynamic therapy.
Received 7 September 2006; received after revision 17 October 2006; accepted 31 October 2006 相似文献
9.
The prolyl oligopeptidase family 总被引:6,自引:0,他引:6
Polgár L 《Cellular and molecular life sciences : CMLS》2002,59(2):349-362
A group of serine peptidases, the prolyl oligopeptidase family, cannot hydrolyze peptides containing more than about 30 residues.
This group is unrelated to the classical trypsin and subtilisin families, and includes dipeptidyl peptidase IV, acylaminoacyl
peptidase and oligopeptidase B, in addition to the prototype prolyl oligopeptidase. The recent crystal structure determination
of prolyl oligopeptidase (80 kDa) has shown that the enzyme contains a peptidase domain with an α/β hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed β-propeller. This domain operates as a gating filter, excluding large, structured peptides from the active site. The binding
mode of substrates and the catalytic mechanism differ from that of the classical serine peptidases in several features. The
members of the family are important targets of drug design. Prolyl oligopeptidase is involved in amnesia, depression and blood
pressure control, dipeptidyl peptidase IV in type 2 diabetes and oligopeptidase B in trypanosomiasis.
Received 8 August 2001; received after revision 19 September 2001; accepted 21 September 2001 相似文献
10.
Francesca Cherubino Andreea Miszner Maria Daniela Renna Rachele Sangaletti Stefano Giovannardi Elena Bossi 《Cellular and molecular life sciences : CMLS》2009,66(23):3797-3808
The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied
with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (γ-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated
current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially
unaffected. The efficacy of desipramine, but not of the other drugs, is strongly increased in the lysine-glutamate or -aspartate
mutants K448E and K448D. Comparison of I
max and K
0.5GABA in the absence and presence of desipramine showed that both parameters are reduced by the drug in the wild-type and in the
K448E mutant. This suggests an uncompetitive inhibition, in which the drug can bind only after the substrate, an explanation
in agreement with the lack of effects on the pre-steady-state and leak currents, and with the known structural data. 相似文献
11.
H. E. Enesco M. A. Enesco E. Aloj Totaro F. A. Pisanti 《Cellular and molecular life sciences : CMLS》1988,44(8):712-713
Summary Treatment with acetylhomocysteine thiolactone significantly reduces the cellular level of lipofuscin in neurons of the electric lobe ofTorpedo marmorata. At the same time, this drug produces a 45% decrease in nucleolar volume in these neurons, reflecting decreased cellular synthetic activity. 相似文献
12.
This review describes the structure and function of prolyl endopeptidase (PEP) enzymes and how they are being evaluated as
drug targets and therapeutic agents. The most well studied PEP family has a two-domain structure whose unique seven-blade
β-propeller domain works with the catalytic domain to hydrolyze the peptide bond on the carboxyl side of internal proline
residues of an oligopeptide substrate. Structural and functional studies on this protease family have elucidated the mechanism
for peptide entry between the two domains. Other structurally unrelated PEPs have been identified, but have not been studied
in detail. Human PEP has been evaluated as a pharmacological target for neurological diseases due to its high brain concentration
and ability to cleave neuropeptides in vitro. Recently, microbial PEPs have been studied as potential therapeutics for celiac sprue, an inflammatory disease of the small
intestine triggered by proline-rich gluten.
Received 6 July 2006; received after revision 17 August 2006; accepted 1 November 2006 相似文献
13.
Summary This is the first report of induction of haploidization inAspergillus nidulans by chloral hydrate, which is an efficient polyploidizing agent for higher plants and a psychotropic drug for man. A new procedure has been described to isolate haploids from diploids with a very high frequency, as compared top-fluorophenylalanine, which is generally used for this purpose. 相似文献
14.
J. T. A. Leuschner D. R. Wing Dr. D. J. Harvey G. A. Brent C. E. Dempsey A. Watts W. D. M. Paton 《Cellular and molecular life sciences : CMLS》1984,40(8):866-868
Summary
1-Tetrahydrocannabinol (
1-THC) has been quantified directly in erythrocyte membranes from drug-treated mice using gas chromatography/mass spectrometry. Concentrations of approximately 6 ng
1-THC/mg membrane protein (10–5 M) were found when effects of the drug on behavior were prevalent. At these concentrations the drug produced a decrease in membrane order as measured by ESR.This work was supported by grants from the Medical Research Council, the Wellcome Trust and the E. P. Abraham Cephalosporin Trust 相似文献
15.
S. G. Goijman J. F. Turrens G. B. Marini-Bettolo A. O. M. Stoppani 《Cellular and molecular life sciences : CMLS》1985,41(5):646-648
Summary Tingenone and horminone, two natural quinonoid substances, inhibited the in vitro growth ofTrypanosoma cruzi, 30 M drug concentration producing total inhibition of growth. Tingenone inhibited total uptake and incorporation of [3H]thymidine, [3H]uridine, L-[3H]leucine into parasite macromolecules. Other quinonoids assayed were either less effective (abruquinone A) or even quite inactive (visminone B and ferruginin B). Investigation of several mechanisms for the cytotoxic action of tingenone pointed to the interaction with DNA as the most likely factor involved. Tingenone also inhibited the growth ofCrithidia fasciculata, but the drug was significantly less active on this organism than onT. cruzi.This work was supported by grants of UNDP/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, Organization of American States (Multinational Programme of Biochemistry) and Programa Nacional de Enfermedades Endémicas (SECYT), República Argentina. A preliminary account was given at the Workshop on Oxidative Damage and Related Enzymes, Frascatti (Italy), 1983. 相似文献
16.
Summary The influence of Desipramin on ERG and optic nerve activity (42 single neurons) was studied in 8 cats. The drug strongly suppressed the spontaneous activity of the neurons, leaving the response to illumination practically uninfluenced. Thec-wave of the ERG was increased. There is little doubt about a pure retinal origin of the effects. 相似文献
17.
A. Jearnpipatkul P. Govitrapong Y. Yuthavong P. Wilairat B. Panijpan 《Cellular and molecular life sciences : CMLS》1980,36(9):1063-1064
Summary Chloroquine, quinacrine and mefloquine bind toPlasmodium berghei hemozoin, hemin, heme, protoporphyrin IX and protease digested methemoglobin. This binding may be the basis for drug accumulation and action in the parasite.Acknowledgments. We thank the World Health Organization, the National Research Council of Thailand and Mahidol University for financial support. Dr Prapin Wilairat's suggestions are appreciated. 相似文献
18.
E. J. Burden S. G. Carvajal P. F. Fabio T. L. Fields Yang-I Lin K. C. Murdock S. A. Lang Jr 《Cellular and molecular life sciences : CMLS》1979,35(1):33-35
Summary Bisamidines of 2,6-diaminoanthraquinone have demonstrated potent activity against cecal and hepaticEntamoeba histolytica infections in rats and hamsters, respectively. A number of these compounds compared favorably, in overall drug efficacy, with metronidazole and other standard agents.Acknowledgements. The authors wish to thank Dr B. Jackson and co-workers for the results in the Dominant-Lethal test and N.A. Kuck for the results in the Ames test. 相似文献
19.
Summary Methallibure treatment is as effective as hypophysectomy in reducing thyroid activity inH. fossilis. Sex steroids (TP and EB) administration restored thyroid activity in methallibure-treated females to normal level, but failed to elicit any response in males. This drug seems to block TSH secretion and thyroid hormone synthesis inH. fossilis.Financial assistance in the form of SRF from ICAR, New Delhi to one of us (R.B.R.), gift of methallibure from ICI Ltd., UK and TSH from NIH, USA, to T.P.S. are gratefully acknowledged. 相似文献
20.
J. L. Lacuara S. R. de Barioglio P. P. de Oliva A. S. Bernacchi A. F. de Culasso J. A. Castro B. M. Franke de Cazzulo J. J. Cazzulo 《Cellular and molecular life sciences : CMLS》1991,47(6):612-616
Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100 M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 M TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug. 相似文献