Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

Biological properties of interleukin-12 and its therapeutic use in persistent hepatitis B virus and hepatitis C virus infection

Summary. Interleukin (IL)-12 is a pleiotropic cytokine produced by antigen-presenting cells in response to diverse stimuli. IL-12 is a key molecule in the regulation of host's immune responses. In particular, IL-12 influences the balance between the T-helper cells type 1 (TH₁) and type 2 (TH₂); it modulates macrophage responses through the control of interferon-gamma synthesis by TH₁ cells; and, suppresses IgE class antibody production (has a suppressive effect on allergic reactions) and promotes a shift in the IgG subclasses. IL-12 enhances resistance to several infectious diseases, is a powerful antitumor agent in vivo , and acts as a vaccine adjuvant. The biological properties of IL-12 point to the potential therapeutic use in persistent hepatitis B virus and hepatitis C virus infection.     

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

The multifunctionality of FGF-2 in the adrenal medulla

 Chromaffin cells of the adrenal medulla and their tumor counterparts, the pheochromocytoma (PC12) cells, are well-established model systems in neurobiology. The development of sympathoadrenal progenitor cells to chromaffin cells can be studied with regard to developmental signals which trigger the differentiation. With regard to potential treatments of neurological disorders like Parkinson’s disease chromaffin cell grafting can be used as one therapeutical approach. The beneficial effect of chromaffin cell grafts is possibly not only related to the release of dopamine but may also be linked to the release of growth factors. One of the growth factors that is synthesized by chromaffin and PC12 cells is basic fibroblast growth factor (FGF-2). The experimental data available so far, are in agreement with different functional roles of FGF-2. This article summarizes the putative physiological functions of FGF-2 in the adrenal medulla. Three differential functional roles of FGF-2 are discussed: (1) as a differentiation factor for sympathoadrenal progenitor cells; (2) as a target-derived neurotrophic factor for preganglionic sympathetic neurons which innervate adrenal medullary cells; (3) as an auto-/paracrine factor in the adrenal medulla. Accepted: 21 August 1996     

Cytokine Production by Lymphocytes in Pregnancy

PROBLEM: In the presence of progesterone lymphocytes of pregnant women release a 34- kDa protein named the progesterone-induced blocking factor (PIBF). PIBF mediates the immunomodulatory and anti-abortive effects of progesterone and its presence is related to the outcome of pregnancy. PIBF induces production of Th2 type cytokines by activated lymphocytes. The in vivo relationship between PIBF- and cytokine production of pregnancy lymphocytes and the outcome of pregnancy was investigated. METHOD OF STUDY: Interleukin (IL)-12 and IL-10 production and PIBF expression in peripheral lymphocytes of 111 healthy pregnant women and 120 women at risk for premature pregnancy termination were detected by immunocytochemistry. RESULTS: We found increased IL-12 and low PIBF and IL-10 expression on lymphocytes of “risk” patients, and a high rate of IL-10 and PIBF positivity on lymphocytes from healthy pregnant women. The cytokine production pattern of the lymphocytes was related to the presence or absence of previous abortions as well as to the outcome of pregnancy. CONCLUSION: These data suggest the involvement of an altered cytokine production pattern in the immunologic effects of progesterone.     

Antiviral triterpenes fromPrunella vulgaris

Two triterpenes 1 and 2 with antiviral activity againstHerpes simplex virus type 1in vitro were isolated fromPrunella vulgaris. Each compound caused a significant reduction in viral cytopathic effect whenvero cells were exposed to them for 72 hours after viral challenge. They were identified asbetulinic acid(1) and 2α, 3α-dihydroxyurs-12-en-28-oic acid(2) on the basis of their spectroscopic properties. The antiviral activity of them was estimated as EC₅₀=30 μg/ml(1) and 8 μg/ml(2), respectively by plaque reduction assay.     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Myoblast fusion in Drosophila melanogaster is mediated through a fusion-restricted myogenic-adhesive structure (FuRMAS).

During myogenesis in Drosophila embryos, a prominent adhesive structure is formed between precursor cells and fusion-competent myoblasts (fcms). Here, we show that Duf/Kirre and its interaction partners Rols7 (found in founder myoblasts and growing myotubes) and Sns (found in fcms) are organized in a ring-structure at the contact points of fcms with precursor cells, while cytoskeletal components like F-actin and Titin are centered in this ring in both cell types. The cytoplasmic protein Blow colocalizes with the actin plugs in fcms after cell adhesion. Furthermore, the requirement of additional as yet unidentified components was demonstrated by using mammalian C2C12 myoblasts. In this study, we propose that the fusion-restricted myogenic-adhesive structure (FuRMAS) is pivotal in linking cell adhesion as well as local F-actin assembly and dynamics to downstream events that ultimately lead to plasma membrane fusion. Moreover, we suggest that the FuRMAS may restrict the area of membrane breakdown.     

高效液相法测定金樱子中三萜酸类成分的含量

定量测定不同产地金樱子中2α,3α,19α,23-四羟基乌苏-12-烯-28-羧酸的含量.采用高效液相法,色谱柱:Kromasil-C18(4.6 mm×250 mm,5 μm)柱,大连依利特公司;检测波长203 nm,柱温:35 ℃;流动相:乙腈-水(35:65),流速1 mL/min.结果表示所测成分与其他组分具有良好的分离度,线性范围为0.4～10 μg, 加样回收率为102.5%,RSD=2.66%.说明不同产地的三萜类有机酸的含量差别很大.本方法操作简单,结果准确,可用于含2α,3α,19α,23-四羟基乌苏-12-烯-28-羧酸的药物的含量测定.     

异丙酚对布比卡因诱导的PC12细胞毒性的作用

目的 探讨异丙酚对布比卡因诱导的PC12细胞毒性的作用及其可能机制。方法PCI2细胞接种于96孔培养板中培养，随机分为4组：对照组、布比卡因组、异丙酚组和布比卡因＋异丙酚组，分别加入Hanks液、布比卡因（终浓度为0．03、0．06、0．09、0．12、0．15mmol／L）、异丙酚（终浓度为1、2,4、8mmol／L）以及同时加入布比卡因（终浓度为0．09mmol／L）和异丙酚（终浓度为1、2,4、8mmol／L）。培养24h时，采用二甲基噻唑二甲基四唑溴盐比色微量分析法测定各孔的细胞活力和上清液乳酸脱氢酶（LDH）的活性，应用流式细胞仪检测硫氧还蛋白-1（Trx-1）和硫氧还蛋白还原酶-1（TrxR-1）表达率。结果 与对照组比较，布比卡因组PC12细胞活力降低（P〈0．01），且呈浓度依赖性；异丙酚组PC12细胞活力差异无统计学意义（P〉0．05）。与布比卡因组的0．09mmol／L亚组比较，布比卡因＋异丙酚组的2—8mmol／L亚组PC12细胞活力增加（P〈0．05）。与对照组比较，布比卡因组和布比卡因＋异丙酚组LDH活性升高，Trx-1和TrxR-1表达率降低（P〈0．01）；与布比卡因组比较，异丙酚组和布比卡因＋异丙酚组LDH活性降低，Trx-1和TrxR-1表达率升高（P〈0．01）。结论 布比卡因对PC12细胞具有浓度依赖性的细胞毒性作用。异丙酚可通过保护内源性硫氧还蛋白系统减轻布比卡因诱导的PCI2细胞的毒性。