Asthma and anaphylaxis induced by royal jelly

Background Asthma, together with, In some cases, anaphylaxis, was observed in seven subjects following ingestion of royal jelly, a secretion of honey bees which is used as a health tonic. Objective To determine if reactions were lgE-mediated and to identify ailergenic components of royal jelly. Methods Skin-prick tests, immunoassays for specific IgE antibodies and protein blotting studies using patients’ sera and anti-IgE second antibodies were employed. Results Immunoassays detected IgE antibodies to royal jelly proteins in sera of subjects who reacted to the substance. A total of 18 different IgE-binding components were detected on blots following electrophoretic separation of royal jelly under dissociating conditions. Examination of 63 sera from subjects allergic to bee venom showed that there is no direct relationship between IgE antibody reactivity to bee venom allergens and to royal jelly proteins although 38% of the sera reacted with a royal icily solid phase. IgE antibody reactivity to royal jelly proteins was also detected in 52% of 75 subjects with allergies to inhalant and/or food allergens. Antibody binding of blotted royal jelly proteins was most marked in the molecular weight region 25–55 kDa and one component of MW～55 kDa was detected by all of the reactive sera from roya jelly-allergic and control allergic subjects. Conclusions Symptoms of asthma and anaphylaxis seen in subjects following ingestion of royal jelly were true IgE-mediated hypersensitivity reactions. The clinical significance of the antibodies found in the sera of control subjects is not known but they may arise in response to common inhalant allergens that show allergenic cross-reactivity with royal jelly.     

Hepatoprotective effects of lobenzarit disodium on acetaminophen-induced liver damage in mice

We have studied the effects of the immunomodulator drug lobenzarit in the model of acute hepatotoxicity induced by a high oral dose (600 mg/kg) of acetaminophen in mice. Lobenzarit at doses of 25, 50 and 100 mg/kg i.p. decreased significantly the activity of alanine aminotransferase in serum, which was increased by acetaminophen alone, and increased the concentration of reduced glutathione in mice liver, which is depleted by acetaminophen.Lobenzarit also reduced liver damage induced by acetaminophen in mice, which was observed by electron microscopy. The hepatoprotective effects of lobenzarit were dose-dependent and they were produced when lobenzarit was administered 30 min before acetaminophen or 2 and 4 h after it. It is concluded that lobenzarit exerts some effects which resemble those of an antidote of acetaminophen such asN-acetylcysteine.     

Osteoinductive and anti-inflammatory effect of royal jelly on periodontal ligament cells

Royal jelly (RJ) has been reported to possess several physiological and pharmacological properties such as the ability to prevent osteoporosis in rats and anti-inflammatory effects. We hypothesized that RJ could have beneficial effects on the prevention or treatment of periodontal diseases, which are chronic inflammatory diseases caused by bacterial infection that result in resorption of the tooth-supporting bone. We assessed the effect of RJ on mineralization in mouse periodontal ligament cell clone 22 (MPDL22 cells), which are of an osteogenic and cementogenic lineage. The mRNA expression of osteopontin, osteocalcin and osterix, and mineralized nodule formation were significantly enhanced in RJ-treated MPDL22 cells. In addition, we investigated the effects of RJ on the production of inflammatory cytokines from MPDL22 cells stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a periodontopathic bacterium. RJ suppressed LPS-induced interleukin-6 and CXC chemokine ligand 10 production from MPDL22 cells. Furthermore, RJ suppressed the expression of CD54 in MPDL22 cells: CD54 is the adhesion molecule involved in the accumulation of leukocytes in periodontal lesions. These findings suggest that the osteoinductive and anti-inflammatory effects of RJ can provide benefits for the treatment and prevention of periodontal diseases.     

Evaluation of the immunomodulatory activities of royal jelly components in vitro

In this work the effect of different components isolated from royal jelly (RJ) was studied using an in vitro rat T-cell proliferation assay. We found that lower concentrations of MEL 174 (final water extract of RJ) and MEL 147 (3-10-dihydroxydecanoic acid) stimulated T-cell proliferation, triggered by concanavalin A (Con-A) and the process was followed by an increase in the production of interleukin-2 (IL-2). Higher concentrations of MEL 174, MEL 247 (dry powder of RJ) and MEL 138 (trans-10-hydroxydec-2-enoic acid) inhibited T-cell proliferation. The inhibition of T-cell proliferation in the presence of MEL 174 was followed by a decrease in IL-2 production, which was partly abrogated by exogenous IL-2, a decrease in nitric oxide (NO) production and increased apoptosis. In conclusion, our results showed the complexity of biological activity of RJ and suggest that its water extract possesses the most potent immunomodulatory activity in vitro.     

磷酸组织胺诱导的Ⅰ型超敏反应对肝损伤作用的研究

目的:通过观察与Ⅰ型超敏反应相关的生物活性介质--组织胺对家兔肝脏有无直接损伤作用,进一步论证Ⅰ型超敏反应对肝脏的损伤作用.方法:选择34只家兔随机分为对照组、实验Ⅰ组和实验Ⅱ组3组;对照组只进行正常饲料喂养,实验Ⅰ组在正常饲料喂养的同时每天给予0.4μg/kg耳静脉注射磷酸组胺注射液,实验Ⅱ组在正常饲料喂养的同时每天给予0.08 μg/kg耳静脉注射磷酸组胺注射液;动态观察以上3个组的血清谷丙转氨酶(ALT)及血清谷草转氨酶(AST)变化;利用光学显微镜观察以上3个组肝组织的病理变化.结果:无论是实验Ⅰ组或实验Ⅱ组,经过一段时间的观察,发现血清内ALT和AST含量均显着高于对照组(P＜0.01),但Ⅰ、Ⅱ组之间无显着性差异(P＞0.05);实验Ⅰ组和实验Ⅱ组在显微镜下观察,其肝脏均有不同程的损伤和病理改变,且实验Ⅱ组的损伤和变化大于实验Ⅰ组,而对照组的肝脏则无明显的病理变化.结论:组织胺对家兔肝脏确实有一定的损伤作用,而且随着投予剂量和时间的增加,肝脏的损伤和病理变化也越显著;通过本研究,可以得出Ⅰ型超敏反应导致肝脏病理变化及损伤的见解.     

Ultrastructural study of liver cell damage induced by ricin.

Experiments were carried out on female albino (Wistar) rats to establish ricin's liver damaging effect. In accordance with the data in the literature it seems that: 1. 2 microg/kg i.p. ricin (investigated 24 h later of its administration) has a detectable hepatotoxic effect; i.e. electron density changes of cells and swelling of mitochondria. These findings correspond to the common and first ultrastructural signs of liver cell damage. This result was further strengthened by the fact that serum ALT and AST values were significantly elevated compared to the control value. 2. The next steps of ricin's damaging effect have been detected at 10 microg/kg i.p. dose,--namely: Effect on smooth endoplasmic reticulum: in its place there is a loose, foam-structured unidentified material,--while in the granulated endoplasmic reticulum the number of ribosomes decreased, similarly to the glycogen granules. 3. 200 microg/kg i.p. ricin caused a severe liver-cell damage. The mitochondria showed early degenerative signs,--and both endoplasmic reticulums were further damaged. The most significant feature is the complete lack of ribosomes in the tubular structure of the granulated endoplasmic reticulum. This latter finding enlights the known inhibitory effect of ricin on protein synthesis. The serum enzyme-levels remained in the pathological range. No early sign of enzyme (Cytochrome P450,) induction could be observed.     

Protection of mice against endotoxin-induced liver damage by anti-inflammatory drugs

Mice were injected withCorynebacterium parvum, which induces multiple granulomas in liver and renders animals hyper-reactive to the lethal effect of bacterial lipopolysaccharide (LPS). Such animals when challenged with LPS developed also extensive liver parenchymal cell damage as estimated by elevated blood aspartate transaminase levels and a hypoglycaemia. Treatment with indomethacin, hydrocortisone, dexamethasone, promethazine, metiazinic acid and (+)-catechin ameliorated the liver damage. Hydrocortisone, cortisone, dexamethasone, promethazine and metiazinic acid also reduced the mortality rate in mice challenged with LPS. Diarrhoea, accompanying the LPS-induced shock, was prevented by the drugs used. Possible agents mediating the hepatotoxic and shock effects of LPS are discussed.     

Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage

ESCs are a potential cell source for cell therapy. However, there is no evidence that cell transplantation using ESC-derived hepatocytes is therapeutically effective. The main objective of this study was to assess the therapeutic efficacy of the transplantation of ESC-derived endodermal cells into a liver injury model. The beta-galactosidase-labeled mouse ESCs were differentiated into alpha-fetoprotein (AFP)-producing endodermal cells. AFP-producing cells or ESCs were transplanted into transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Selective damage was induced in the recipient hepatocytes by the administration of DT. Although the transplanted AFP-producing cells had repopulated only 3.4% of the total liver mass 7 days after cell transplantation, they replaced 32.8% of the liver by day 35. However, these engrafted cells decreased (18.3% at day 40 and 7.9% at day 50) after the cessation of DT administration, and few donor cells were observed by days 60-90. The survival rate of the AFP-producing cell-transplanted group (66.7%) was significantly higher in comparison with that of the sham-operated group (17.6%). No tumors were detected by day 50 in the AFP-producing cell-transplanted group; however, splenic teratomas did form 60 days or more after transplantation. ESC transplantation had no effect on survival rates; furthermore, there was a high frequency of tumors in the ESC-transplanted group 35 days after transplantation. In conclusion, this study demonstrates, for the first time, that ESC-derived endodermal cells improve the survival rates after transplantation into mice with induced hepatocellular injury. Disclosure of potential conflicts of interest is found at the end of this article.     

Lesions of the renal papilla induced by paracetamol

The acute nephrotoxic effects of paracetamol in the uninephrectomized homozygous Gunn rat are different from those of aspirin. Both compounds induce renal papillary necrosis but paracetamol produces accumulation of non-cellular material in the interstitial space, less damage to interstitial cells, more damage to tubular epithelium, and more severe necrosis of proximal convoluted tubules. In both cortex and papilla only a small fraction of the cells at risk are affected. It is concluded that the findings are consistent with a synergistic nephrotoxic effect between the two compounds, but that the lesions are not sufficiently severe for the natural history of analgesic nephropathy to be wholly explicable by such synergism.     

毛蕊花糖苷对顺铂诱导小鼠卵巢损害的保护作用

目的研究毛蕊花糖苷对顺铂所致卵巢损害的保护作用。方法 48只昆明雌性小鼠随机分成4组:对照组、顺铂组、顺铂+毛蕊花糖苷低浓度干预组及顺铂+毛蕊花糖苷高浓度干预组。顺铂组、顺铂+毛蕊花糖苷干预组,分别给予腹腔注射顺铂(2.0 mg/kg·d),同时给予等体积生理盐水及不同浓度毛蕊花糖苷(30、60 mg/kg·d)灌胃处理。干预一周后,停止腹腔注射顺铂,毛蕊花糖苷持续干预一周。对照组小鼠给予同等剂量的生理盐水腹腔注射及灌胃处理。分别通过ELISA方法检测各组小鼠血中雌激素(estradiol,E2)及促卵泡激素(follicle-stimulating hormone,FSH)水平、HE染色观察卵巢形态结构、TUNEL染色检测卵巢细胞凋亡情况、免疫组化法及Western blot方法检测卵巢组织中凋亡相关蛋白(cleaved-caspase 3、cleaved-PARP)的表达水平。结果顺铂组小鼠可见血FSH水平升高,卵巢可见发育中窦状卵泡内的颗粒细胞层明显减少,卵母细胞核碎裂及闭锁卵泡增加;凋亡相关蛋白cleaved-caspase 3、cleaved-PARP的表达水平升高,而毛蕊花糖苷药物干预后在一定程度上能逆转卵巢功能及结构损害,并使卵巢凋亡相关蛋白下调来抑制卵巢组织的凋亡。结论毛蕊花糖苷具有对抗顺铂所致卵巢组织凋亡,保护化疗药物引起的卵巢功能损伤的作用。     

Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats

To assess the usefulness of oncostatin M (osm) gene therapy in liver regeneration, we examined whether the introduction of OSM cDNA enhances the regeneration of livers damaged by dimethylnitrosamine (DMN) in rats. Repeated injection of OSM cDNA enclosed in hemagglutinating virus of Japan envelope into the spleen resulted in the exclusive expression of OSM protein in Kupffer cells of the liver, which was accompanied by increases in body weight, liver weight, and serum albumin levels and the reduction of serum liver injury parameters (bilirubin, aspartate aminotransferase, and alanine aminotransferase) and a serum fibrosis parameter (hyaluronic acid). Histological examination showed that osm gene therapy reduced centrilobular necrosis and inflammatory cell infiltration and augmented hepatocyte proliferation. The apoptosis of hepatocytes and fibrosis were suppressed by osm gene therapy. Time-course studies on osm gene therapy before or after DMN treatment showed that this therapy was effective not only in enhancing regeneration of hepatocytes damaged by DMN but in preventing hepatic cytotoxicity caused by subsequent treatment with DMN. These results indicate that OSM is a key mediator for proliferation and anti-apoptosis of hepatocytes and suggest that osm gene therapy is useful, as preventive and curative means, for the treatment of patients with liver damage.     

Differential effects of dipyrone,ibuprofen, and paracetamol on experimentally induced pain in man

In a double-blind cross-over study on 22 healthy subjects the analgesic efficacies of the antipyretic analgesic drugs ibuprofen, dipyrone and paracetamol were tested against placebo using a model of experimentally induced pain. To this purpose interdigital webs were pinched repeatedly for 2 min periods. The painfulness of these stimuli was assessed by the subjects on an electronically controlled visual analogue scale at 10 sec intervals. In addition to the subjective pain rating the stimulus induced reflex diminution of the blood flow in the stimulated hand was measured with photoplethysmography and laser Doppler flow analysis. The flare response around the stimulated area was assessed with infrared thermography. In this assay system ibuprofen and dipyrone, but not paracetamol, showed statistically significant analgesic effects by preventing hyperalgesia which is normally induced by the repeated stimulation of a skin site. This hypoalgesic effect was not related to the subjective impression of the subjects of the analgesic potency of the respective drug. Sympathetic reflex vasoconstriction was not quantitatively related to the drug induced hypoalgesia. Ibuprofen and, to a minor extent, the other antipyretic analgesic drugs also diminished the stimulus induced flare reaction around the stimulated skin sites.     

四氯化碳诱导的肝损伤对大鼠免疫机能的影响

目的:研究化学性肝损伤对机体免疫机能的影响。方法:选择30只健康、1月龄、平均体重(83.20±2.11) g雌雄各半SD大鼠,经一段时间适应性饲养后,随机分成四氯化碳(CCl₄)注射组和对照组。CCl₄注射组大鼠按0.2 mL/100 g体重剂量每周定时注射CCl₄ 2次, 连续注射8周;对照组同时注射等量的橄 榄油。观察CCl₄诱导的肝损伤对机体免疫功能的影响。结果:注射CCl₄大鼠外周血T淋巴细胞比例和白细胞介素2水平显著低于对照组,与此同时B淋巴细胞比例却显著高于对照组;注射CCl₄组大鼠血浆总蛋白含量和白蛋白、α和β球蛋白比例下降,而γ球蛋白上升。结论:CCl₄诱导的肝损伤能明显影响大鼠的细胞免疫和体液免疫功能,造成大鼠的免疫功能失调。     

Biliary hyperplasia and carcinogenesis in chronic liver damage induced in rats by phomopsin

Phomopsin, a hexapeptide mycotoxin contaminant of lupin plant and seed materials, was administered subcutaneously to adult rats at a daily dose rate of 30 micrograms/kg body weight (approximately 0.005 median lethal dose) for 2, 6 or 17 wks and the development of liver damage was observed during treatment and for up to 2 yr after. All rats injected for 17 wks developed permanent liver damage characterized by nodular cirrhosis and extensive biliary hyperplasia. Cholangiomas developed in 60% of these rats and cholangiocarcinomas and hepatocellular carcinomas in 13%. Similar effects were produced in some rats injected for 6 wks, while in others the cessation of treatment was followed by almost complete regression of the liver lesions. Livers damaged by 2 wks of injection had fully recovered within a few wks. The permanence of the liver damage is relevant to the management of stock exposed seasonally to the toxin, while its carcinogenic potential in rats, although not high, indicates the need for monitoring of the phomopsin content of lupin seed or flour prepared for human consumption.     

细胞共培养条件下大鼠肌源性干细胞对氧化应激损伤神经元的保护作用

目的:研究肌源性干细胞(MDSCs)与氧化应激损伤神经元共培养条件下MDSCs对后者的保护作用。方法:分离新生SD大鼠的MDSCs及皮层神经元,以叔丁基过氧化氢损伤神经元,构建氧化应激损伤的神经元模型。实验分为2组,损伤组:将第5代MDSCs和损伤的神经元置于共培养系统中培养4 h;对照组:损伤神经元于共培养系统中单独培养4 h。培养7 d后通过Hoster33258及流式细胞仪检测第2、4、6 d各组神经元的存活率,并用RT-PCR对相关基因进行分析,探究差异的内在原因。结果:Hoster33258及流式细胞仪检测结果显示:在共培养2、4、6 d三个时间点损伤组的神经元的存活率要远远高于对照组(P<0.05),凋亡率明显低于对照组,RT-PCR检测到损伤组神经元在三个时间点Bcl-2的表达水平均较对照组强(P<0.05),而Bax的表达水平均较对照组低(P<0.05)。结论:在共培养条件下,MDSCS对氧化应激损伤神经元具有保护作用,而这与其可促使损伤神经元Bcl-2的表达水平升高以及抑制Bax的表达有关。