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Biomedical subjects

Y Fang

Publications and source records attributed to Y Fang.

At least 235 records · Page 13Linked to original sources

[Studies on anti-tumor agents. I: Synthesis and anti-cancer activity of amino acid derivatives of norcantharidin].

In order to search for new compounds with higher anti-cancer activities and lower toxicities, 19 amino acid derivatives of norcantharidin, of which 16 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that 2-(syn-exo-7-oxabicyclo [2.2.1] heptane-2,3-dicarboxylic imido)-N-phenyl glutaramic acid exhibited a fairly apparent inhibitory activity against human-hepatoma cells in vitro (inhibitory rate 39.4% at 0.025 mumol/ml).

Animals↗

[Studies on antitumor agents II: synthesis and anticancer activity of dehydrogenated carboncyclic analogs of norcantharidin].

In order to search for new compounds with higher anti-cancer activities and lower toxicities, 18 dehydrogenated carboncyclic analogs of norcantharidin, of which 17 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that compound V6, VI1 and VI4 exhibited fairly apparent inhibitory activity against the growth of human-hepatoma cells, Bel-7402, in vitro. The inhibitory rate of VI4 is 52%, almost the same as that of norcantharidin, in the concentration of 0.05 mumol/ml.

Antineoplastic Agents↗

[Studies on the establishment of malarial animal model of short-term relapse. III. Combined therapy with pyronaridine-artemether-chloroquine for parasitemia clearance].

To establish a Plasmodium cynomolgi-monkey model of short-term relapse, different antimalarials have been used to inhibit recrudescence so as to elude the confusion between the two different onsets. When a single dose of effective schizonticides pyronaridine, artemether or chloroquine was administered, recrudesence readily occurred. This paper reports the results of the combined therapy with the above three drugs. Seven rhesus monkeys from Guangxi Autonomous Region infected with Plasmodium cynomolgi from Vietnam by blood transmission were rapidly cured by combined therapy with pyronaridine 6 mg/kg-artemether 100 mg/kg-chloroquine 10 mg/kg (PAC-1) once daily for 3 days. The average time of parasite clearance was 3.43 +/- 0.89 d and the curvilinear regression equation of parasite density after treatment was Y = 10(3.94-0.83X). Severe side effects of the gastrointestinal tract occurred during the course of treatment, though no recrudescence was found after 300-400 days. To reduce the side effects, another test was carried out in 3 monkeys and the dosage regimen was modified to pyronaridine 6 mg/kg-artemether 10 mg/kg-chloroquine 20 mg/kg (PAC-2) once daily for 3 days. There was no obvious side effect in the tested monkeys and the parasites were cleared during a mean time of 2.67 +/- 0.58 d and the curvilinear regression equation of parasite density was Y = 10(3.7-1.46X). No recrudescence was detected in the animals during a follow-up of 180 days. The study shows that PAC-2 regimen of the combined therapy is effective for parasitemia clearance and might be adopted for establishment of the monkey model of short-term relapse.

Animals↗

IL-4 synthesis by in vivo primed keyhole limpet hemocyanin-specific CD4+ T cells. I. Influence of antigen concentration and antigen-presenting cell type.

The development of IL-4 synthesis is a critical step in the regulation of immune responses. Our studies focused on the production of IL-4 by CD4+ T cells taken from mice primed with the Ag keyhole limpet hemocyanin (KLH). In vitro stimulation of such CD4+ T cells with KLH resulted in little or no IL-4 production in the first 24 h of stimulation, indicating that little IL-4 synthesis persists in vivo after immunization. However, IL-4 was generated later at 24 to 96 h of in vitro stimulation, indicating that the potential to produce IL-4 was retained by the KLH-primed CD4+ T cells, but that in vitro maturation of the T cells was required before initiation of IL-4 production. The amount of IL-4 produced in vitro by KLH-primed T cells from BALB/c mice was influenced by several factors. First, stimulation of KLH-primed CD4+ T cells with higher in vitro concentrations of KLH resulted in more IL-4 synthesis, but this was accompanied by more IFN-gamma as well. Second, primed CD4+ T cells from lymph nodes (axillary and popliteal) produced significantly more IL-4 than primed splenic T cells. Third, when primed B cells were utilized to present low concentrations of KLH to the T cells, IL-4 but not IFN-gamma was produced. In contrast, use of splenic adherent cells resulted in IFN-gamma but not IL-4 synthesis. These restricted patterns of lymphokine synthesis, however, were observed only with low concentrations of KLH. Fourth, the amount of IL-4 produced and its regulation by the presence of IFN-gamma differed among mouse strains, in that BALB/c T cells produced much more IL-4 than H-2 identical DBA/2 T cells. Our results characterizing the APC and Ag dose requirements for IL-4 synthesis in KLH-primed T cells from different strains of mice are consistent with previous observations that distinct strains of mice differ in the type of immune response generated against different pathogens, and with the concept that low Ag concentrations preferentially result in high levels of IgE synthesis, which is absolutely dependent on IL-4 production.

Animals↗

The inhibitory effects of 21 mimics of superoxide dismutase on luminol-mediated chemiluminescence emitted from PMA-stimulated polymorphonuclear leukocyte.

Four groups comprising 21 superoxide dismutase (SOD) mimics synthesized by us were comparatively studied for their inhibitory effects on luminol-mediated chemiluminescence emitted from phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocyte (PMNL). Among these groups, 20-membered macrocyclic bicopper(II) complexes and 13-membered macrocyclic dioxotetramine copper(II) complexes exhibited relatively higher activities of scavenging reactive oxygen species (ROS) produced by PMA-stimulated PMNL as compared with polyamine Cu(II)-Zn(II) complexes and copper(II) complexes of bis-shiff-base. Moreover, distinctly different effects of SOD mimics in the biological system have been found even in the same group. It is suggested that the biological effects of some SOD mimics are related to their structures.

Chelating Agents↗

[Studies on the establishment of malarial animal model of short-term relapse. II. The phenomenon of sustained special ring form parasitemia in Plasmodium cynomolgi infection].

Our previous report that the EE merozites of Plasmodium cynomolgi from Vietnam continuously released from the liver to the blood circulation was further demonstrated in this report. Monkeys were given pyronaridine 24 mg/kg.d x 6 after being inoculated intravenously with 32 x 10(5) sporzoites of P. cynomolgi. Thick blood film examination was conducted two times daily till the day when trophozoites were detected. Under the residual action of blood schizontocied, a special ring form parasitemia at low patasite-density was detected for more than 30 days. As the ring forms of P. cynomolgi were demonstrated to be susceptible to pyronaridine in our previous experiments, it might be inferred that these ring forms derived from EE merozites released not for once but continuously for 30 days or longer.

Aminoquinolines↗

[Noradrenaline fluorescence histochemical study on the locus coeruleus of kindling rat induced by coriaria lactone].

Fourteen male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly per 3.5 days. The controls were injected with normal saline. After 26 injections, the loci coeruleus of kindling rats were studied with the noradrenaline (NA) fluorescence histochemical technique at the time between seizures. The NA fluorescence could be clearly visualized under fluorescent microscope. The intensity of fluorescence was reflected by autoexposure-meter of the fluorescent microscope. The brighter the fluorescence, the shorter the autoexposure time. The intensity of NA fluorescence in the locus coeruleus of experimental animals was weaker than that of the controls. Since NA plays an inhibitory role in cerebral cortex, the decrease of NA, either induced by repeated injections of coriaria lactone or due to the time of sample taken after seizure, needs further study.

Animals↗

[Histochemical and image-analytic study of the rat locus coeruleus during status epilepticus].

Twenty-four adult male Wistar rats were used in this study. Status epilepticus was provoked in 10 rats by embedding coriaria lactone particle into the left cerebral motor cortex. In the controls were embedded particles without coriaria lactone. After 6 h of continuous seizure, the locus coeruleus was studied with the noradrenaline (NA) fluorescence histochemical technique and enzyme histochemical test for monoamine oxidase (MAO). The intensity of NA fluorescence was detected with fluorescent microscope autoexposuremeter and analysed with MIAS-200 Image Analyser. The study group showed a parallel increase of NA fluorescence as compared with that of the control group by both measurements. NA plays an inhibitory role in the cortex. Our data suggest that the increase of NA in locus coeruleus may be due to the reduction of NA release from axon terminal. Reduction in inhibition could be one of the mechanisms of seizure activity. The intensity of MAO was detected with MIAS-200 Image Analyser. The regulation of monoamine metabolism by MAO in the central nervous system and the increase of MAO activity in the continuous seizure group may be induced by the accumulation of NA in the locus coeruleus soma.

Animals↗