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Biomedical subjects

Z Gu

Publications and source records attributed to Z Gu.

210 records · Page 12Linked to original sources
PubMed1982

Studies on gossypol. I. Toxicity, antifertility, and endocrine analyses in male rats.

Toxicity, antifertility, and endocrine effects of gossypol have been studied in male rats. The animals grew nearly normally when administered a daily dose of 7.5 mg/kg orally for 12 wk. At 15 and 30 mg/kg/d doses growth rates were significantly reduced. Infertility occurred at all dose levels, but mating behavior was maintained throughout the period of treatment. Examination of the cauda epididymis after 6 wk at the 30-mg/kg/d dose and after 12 wk at the lower doses showed reductions in sperm numbers as compared with controls. All of the sperm from the groups receiving the 15- and 30-mg/kg/d doses were immotile; and at the 7.5-mg/kg/d dose level most sperm were immotile. Many of nonmotile sperm showed sharply bent tails or lacked tails. There was no significant change in the serum levels of testosterone, LH, or FSH in animals receiving 7.5 and 15 mg/kg/d of gossypol for 12 wk. However, at a dose of 30 mg/kg/d for 6 wk, the serum testosterone and LH concentrations were significantly reduced. FSH concentrations remained normal in all groups. A group of 5 animals receiving 15 mg/kg/d were allowed a recovery period of 6 wk after 12 wk of therapy and they evidenced complete recovery of fertility.

Animals↗
PubMed1981

The effect of intrauterine injection of concanavalin A on implantation in mice and rats.

Concanavalin A (Con A) binding sites are present on the surface of blastocysts. When Con A was injected into one uterine horn of the mouse on Day 3 or 5 of pregnancy at 50 or 100 micrograms/horn, or given to the rat on Day 6 or 7 at 200 micrograms/horn, implantation and pregnancy was not affected when compared to the contralateral horn treated with vehicle alone. However, when the same amount of Con A was administered to the mouse on Day 4 or to the rat on Day 5, implantation was significantly decreased, all accompanied by the incidence of deciduomata. The deciduogenicity of Con A is dose-dependent. Also Con A did not affect the development of mouse embryos as a normal number of blastocysts was recovered up to the time of implantation. Thus the inhibition of implantation by Con A could be due to (a) the earlier occurrence of decidual cell response and its subsequent interference with implantation and (b) the involvement of specific sugar groups in implantation.

Animals↗
PubMed1981

The uptake and release of benzo[a]pyrene and benzo[e]pyrene in vitro by Syrian hamster embryo cells as a function of serum concentration.

A quantitative study on the in vitro uptake of benzo[a]pyrene (B[a]P) and benzo[e]pyrene (B[e]P) by Syrian hamster embryo cells and the induction of sister chromatid exchange (SCE) has been carried out. The amounts of B[a]P and B[e]P taken up by the cells decreases as does the induction of SCEs by B[a]P when the concentration of serum in the culture medium increases. It appears that serum prevents (B[a]P or B[e]P uptake. We have observed no significant differences between the two hydrocarbons regarding uptake by cells; chromatographic results show however that B[a]P is metabolized by these cells, while B[e]P is not. Our results suggest that serum inhibits B[a]P and B[e]P uptake and hence decreases the number of SCEs.

Animals↗
PubMed1980

Effects of Gossypol on the fertility of male rats, hamsters and rabbits.

Oral administration of Gossypol acetic acid induced sterility in male hamsters and rats when given at a dose level of 5 or 10 mg/kg daily for 12 weeks. This was shown by the appearance of dead and abnormal sperm in the male tract and the failure of pregnancy or decrease in implantation sites in the females mated to the Gossypol-treated males. Similar treatment of male rabbits at dose levels varying from 1.25 to 10 mg/kg and given for 5 to 14 weeks did not affect the average number of sperm per ejaculate, although the motility of sperm was poor during treatment in some bucks. The pregnancy rates and the proportion of implantation sites were also not affected by insemination of female rabbits with sperm from males during treatment with Gossypol.

Animals↗
PubMedDate not supplied

NGF-mediated alteration of NF-kappaB binding activity after partial immunolesions to rat cholinergic basal forebrain neurons.

There are age-associated cognitive and cholinergic deficits in the neurotrophin-dependent cholinergic basal forebrain neurons (CBFNs). There are also increases in the activity of the transcription factor NF-kappaB in the aged rodent brain that may reflect chronic enhancement of stress response signaling. We used partial immunolesions (PIL) to CBFN to examine the role of endogenous NGF on choline acetyltransferase (ChAT) activity and NGF-mediated NF-kappaB alteration after cholinergic deafferentation. We injected 192 IgG-saporin, an immunotoxin selectively taken up by neurotrophin receptor p75(NTR)-bearing neurons, into lateral ventricles, followed by infusions of anti-NGF to assess NF-kappaB, ChAT and NGF responses to PIL after anti-NGF infusion. Treatment with anti-NGF decreased ChAT activity by 17-34% in the cortex, hippocampus, and olfactory bulb and PIL decreased ChAT activity by 47-73%. Changes in AChE activity levels paralleled those observed for ChAT after PIL. NGF protein levels in the olfactory bulb, but not the cortex or hippocampus, increased significantly after PIL treatment. Infusion of anti-NGF abolished the PIL-induced eight-fold NGF increase in CNS. NF-kappaB binding activity to the IgG-kappaB and ChAT specific NF-kappaB consensus sequences, increased in the cortex but not hippocampus after PIL followed by anti-NGF infusion. It is likely that immunolesion-induced changes in ambient NGF levels may perturb NF-kappaB activity.

Acetylcholinesterase↗
PubMedDate not supplied

Repeated immunolesions display diminished stress response signal.

Cholinergic basal forebrain neurons (CBFNs) retrogradely transport neurotrophins released in the hippocampus and cortex as part of a general response to injury in a process that is impaired in the aged rodent and can be spared by the exogenous addition of pharmacological doses of nerve growth factor (NGF). This observation suggests that components of stress response signal transduction pathways in the aged CNS can be exogenously activated. The extent and mechanism of the endogenous stimulation of NGF in response to injury can be mimicked via treatment with 192 IgG-saporin of rat CNS, an immunolesion model. Here we report on the use of a conditioning lesion paradigm to determine if repeated partial immunolesions have a conditioning effect on the immunolesion-induced increases in NGF protein or decreases in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. We report that chronic repeated immunolesions, as used here, were not as effective as a one time equivalent immunolesion in terms of induced NGF protein increases or decreasing ChAT and AChE activity in the hippocampus and cortex. Thus, chronic lesions resulting in cholinergic impairment typical of the aged CNS may differ from acute toxic models as a result of desensitization due to a conditioning effect of chronic subthreshold lesioning events in the CNS.

Acetylcholinesterase↗
PubMedDate not supplied

Differential alterations of NF-kappaB to oxidative stress in primary basal forebrain cultures.

Oxidative stress has been linked to neuronal cell death resulting from either acute insults due to ischemia, trauma, excitotoxicity, or chronic neurodegenerative diseases. Cholinergic basal forebrain neurons (CBFNs) compete for nerve growth factor (NGF) synthesized in the hippocampus and cortex via retrograde transport. NGF affects CBFN survival and cholinergic function via activation of the NF-kappaB transcription factor and this signaling pathway appears to be impaired in aged rats. Here, we demonstrate that activation of NF-kappaB in basal forebrain primary culture via treatment with hydrogen peroxide or TNF-alpha is predominantly restricted to CBFNs, and that NF-kappaB activation appears to mostly affect p65 translocation to the nucleus, but not the p50 subunit. These results are consistent with NF-kappaB activation being a part of recovery processes after acute oxidative stress. Since p50 or p49 (also called p52) binding to promoter sites does not stimulate transcription - both p50 and p49 lack an activating domain - and p65 does contain an activating domain and thus can act as a transcription enhancer, differential translocation of different NF-kappaB dimers can act as repressors of constitutive activity or enhancers. These results are in agreement with the hypothesis that p50/p65 is the active trans-activating species of NF-kappaB, as compared to p50/p50 homodimers which bind to NF-kappaB binding sites but do not trans-activate promoters. Our results also suggest that selective activation of different NF-kappaB dimer species may have regulatory significance in neuronal responses to acute or chronic insults to CNS. Thus, increased p65 translocation could have enhancing effects while increased p50 translocation could have a repressor role. Manipulation of the types of NF-kappaB species being translocated could provide a basis for therapeutic strategies.

Acetylcholinesterase↗
PubMedDate not supplied

Anti-HIV-1 activities of 1,3-dioxolane guanine and 2,6-diaminopurine dioxolane.

DXG and its prodrug DAPD have been demonstrated to be effective inhibitors of HIV-1 in various cells. The EC50s for DXG were 0.032 microM in CBMCs and 0.05 microM in MT-4 cells, which were generally equipotent as 3TC. 3TC-resistant, but not AZT-resistant, HIV-1 had minimum diminished sensitivity to the compounds. Both DXG and DAPD were non-toxic to cells up to 500 microM.

Anti-HIV Agents↗