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41.
42.
Transition metal complexes containing vanadium IV have been shown to
modulate the cellular redox potential and catalyse the generation of
reactive oxygen intermediates (ROI). Since sperm function is exquisitely
susceptible to ROI, we examined the effects of stable chelate complexes of
vanadocenes on human sperm motility. We synthesized seven structurally
distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with
bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac),
vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene
N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato
monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino
ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)],
and evaluated their spermicidal activity using computer-assisted sperm
analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene
elicited potent spermicidal activity at micromolar concentrations (EC50
values: 3.9-106 microM) without affecting the sperm acrosome integrity. The
catecholate and acetylacetonate complexes of vanadocene were the most
active and the bipyridyl complex the least active with an order of efficacy
VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY.
The spermicidal activity of chelate complexes of vanadocenes was rapid and
irreversible since the treated spermatozoa underwent apoptosis, as
determined by the flow cytometric analysis of mitochondrial membrane
potential, surface annexin V binding assay, in-situ nick-end labelling of
sperm nuclei, and confocal laser scanning microscopy. These results provide
unprecedented evidence that chelate complexes of vanadocene with bidentate
ligands have spermicidal and apoptosis inducing properties. These
vanadocene complexes, especially VDacac, may be useful as contraceptive
agents.
相似文献
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Oberyszyn TM; Conti CJ; Ross MS; Oberyszyn AS; Tober KL; Rackoff AI; Robertson FM 《Carcinogenesis》1998,19(3):445-455
The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate
adherence of leukocytes to vascular endothelium and the associated ligand,
intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2
integrin proteins to allow transendothelial migration of leukocytes into
sites of inflammation. The present study examines the function of these
proteins in a murine model of acute cutaneous inflammation induced
following topical application of 12-O- tetradecanoylphorbol-13-acetate
(TPA) to the dorsal epidermis of SENCAR mice and in a model of skin
multistage carcinogenesis. At 24 h following topical application of TPA to
the dorsal epidermis of mice, dermal leukocytes expressed higher levels of
beta2 integrin protein compared with the lower levels of beta2 integrin
protein expression by peripheral blood leukocytes. ICAM-1 protein was
localized to epidermal keratinocytes and vascular endothelium in
TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.)
injection of either 50 microg anti-beta2 integrin antibody alone or in
combination with anti-ICAM-1 antibody significantly inhibited both
TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and
myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P
< 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but
had no effect on TPA-induced epidermal hyperplasia. In addition, injection
of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in
combination with anti-beta2 integrin antibody (P < 0.001) significantly
inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8-
OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2
integrin/ICAM-1 adhesion molecules work in concert to regulate migration,
retention and functional activation of leukocytes within the dermis during
TPA-induced skin inflammation and within stromal tissue of papillomas that
form during multi-stage carcinogenesis. Agents that inhibit these
receptor/ligand interactions may be useful in defining the roles of
specific cell populations in cutaneous inflammation and multistage
carcinogenesis and may also have potential as anti-promoting and
anti-progression agents.
相似文献
46.
运用Ca2+指示剂Fura-2作为细胞内钙离子的荧光探针,利用AR—CM—MIC阳离子测定系统,检测了分离的神经细胞内游离钙及其变化,并观测了DGAVP和Org2766对蛋白质合成抑制剂茴香霉素(ANI)引起细胞内钙离子浓度([Ca2+]i)变化的影响。结果表明茴香霉素可使[Ca2+]i显著升高,且有量效关系;DGAVP本身并不引起[Ca2+]i发生显著变化,但适当剂量的DGAVP可显著对抗一定剂量范围内ANI升高[Ca2+]i的作用,提示DGAVP对抗ANI的蛋白质合成抑制效应可能是通过拮抗ANI升高[Ca2+]i这一途径实现的,另一神经肽Org2766则可能不是通过这一机制发生作用。从细胞内Ca2+的角度看,这两种肽的作用机理显然是不同的。 相似文献
47.
Robertson RT; Gallardo KA; Claytor KJ; Ha DH; Ku KH; Yu BP; Lauterborn JC; Wiley RG; Yu J; Gall CM; Leslie FM 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(2):142-155
The role of basal forebrain-derived cholinergic afferents in the
development of neocortex was studied in postnatal rats. Newborn rat pups
received intraventricular injections of 192 IgG-saporin. Following survival
periods ranging from 2 days to 6 months, the brains were processed to
document the cholinergic lesion and to examine morphological consequences.
Immunocytochemistry for choline acetyltransferase (ChAT) and in situ
hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the
cholinergic neurons in the medial septum and nucleus of the diagonal band
of Broca in the basal forebrain. In situ hybridization for glutamic acid
decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons.
Acetylcholinesterase histochemistry demonstrates a marked reduction of the
cholinergic axons in neocortex. Cholinergic axons are reduced throughout
the cortical layers; this reduction is more marked in medial than in
lateral cortical areas. The thickness of neocortex is reduced by
approximately 10%. Retrograde labeling of layer V cortico-collicular
pyramidal cells reveals a reduction in cell body size and also a reduction
in numbers of branches of apical dendrites. Spine densities on apical
dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated
cases; no change was detected in number of spines on basal dendrites. These
results indicate a developmental or maintenance role for cholinergic
afferents to cerebral cortical neurons.
相似文献
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Capsular visualization in lipohemarthrosis of the knee 总被引:1,自引:0,他引:1