Lack of tolerance development to tumor necrosis factor α inside the central nervous system

Tumor necrosis factor (TNF) was repeatedly microinfused into the lateral ventricle of guinea pig brains at a dose of 200 ng, 4 times within 150 min, at intervals of 3 days. In comparison to guinea pigs infused with solvent according to the same time schedule, the animals responded to TNF with pronounced fevers. The quantity of the fever response was the same after each of the 4 microinfusions of TNF. Three days after the last infusion of TNF or solvent all animals received an intramuscular injection of bacterial lipopolysaccharide (LPS). The fever in response to LPS was the same in both groups. Thus, the reported development of tolerance to repeated systemic administration of TNF^1–3 does not develop inside the blood-brain barrier. Also, the febrile response to LPS is not influenced by repeated central pre-treatment with TNF, whereas repeated peripheral treatment does have an effect.     

Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes

Summary A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high-up to 1000 and 2000 units ml^–1-and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers.     

变异干髓术的临床疗效分析

变异干髓术是用于治疗乳牙慢性尖周炎的一般方法，现用于治疗恒牙牙髓部分坏死或全部坏死并伴有慢性尖周炎，可以使一些恒牙不作根管治疗且操作简易。１０５０观察时间为０．５－５年，成功８６７年占８２．５％，失败１８３例占１７．５％。     

Tumor necrosis factor as an antineoplastic agent: pitfalls and promises

The discovery and cloning of the cytokine tumor necrosis factor α (TNF) gave rise to new hopes for a significant victory in the war against cancer. Preclinical in vitro studies in cell cultures and in vivo studies in animal models demonstrated the antitumor capacities of TNF. Although clinical studies were largely made possible by the availability of recombinant TNF, phase I and II clinical trials showed very quickly that the systemic administration of TNF induced severe side effects mainly due to its pleiotropic action on immunocompetent cells. The clinical manifestations of the side effects were similar to those observed during a severe infection and inflammation. Very recently, lessons from these clinical studies yielded refined approaches whereby the toxicity of TNF is limited through local administration, a combination with other therapeutic regimens and targeted gene therapy. These new approaches are slated for larger clinical trials and in the near future might demonstrate the limited but powerful usefulness of TNF as an antineoplastic agent for different types of cancer. Received 7 September 1998; received after revision 15 October 1998; accepted 15 October 1998     

Central IL-1 differentially regulates peripheral IL-6 and TNF synthesis

Centrally given interleukin (IL)-1 is known to induce a rapid rises in blood IL-6. To extend this and to examine the mechanism by which this occurs, the effects of intracerebroventricular (icv) injection of human recombinant IL-1β on mRNA expression of IL-6 and tumour necrosis factor (TNF) in the spleen and liver were examined in rats. Icv injection of IL-1 produced a rapid rise of the tissue mRNA levels of IL-6 and TNF in both organs, prior to and/or in parallel with an increase in their serum levels. Pretreatment with chlorisondamine, a ganglionic blocking agent, inhibited the IL-6 responses, while it had little influence on the TNF responses. The results suggest that brain IL-1 induces peripheral production of IL-6, but not of TNF, through autonomic nervous system activation. Received 27 October 1997; received after revision 15 December 1997; accepted 12 January 1998     

Tumor necrosis factor α in the pathogenesis of cerebral malaria

Physiologically in the brain, cytokines such as tumor necrosis factor-alpha (TN) are released by the immune system and can modulate neurological responses. Conversely, the central nervous system (CNS) is also able to modulate cytokine production. In the case of CNS disorders, cytokine release may be modified. Cerebral malaria (CM) is a complication of Plasmodium falciparum infection in humans and is characterized by a reversible encephalopathy with seizures and loss of consciousness. Central clinical signs are partly due to sequestration of parasitized red blood cells in the brain microvasculature due to interactions between parasite proteins and adhesion molecules. TNF is produced and released by host cells following exposure to various malarial antigens. The increase of TNF release is responsible for the overexpression of adhesion molecules. This article reviews the involvement of TNF in cerebral malaria and the relation with all the processes involved in this pathology. It shows that (i) TNF levels are increased in plasma and brain but with no clear correlation between TNF levels and occurrence and severity of CM; (ii) TNF is responsible for intercellular adhesion molecule-1 upregulation in CM, the relation being less clear for other adhesion molecules; (iii) TNF receptors are upregulated in CM, with TNF receptor 2 (TNFR2) showing a higher upregulation than TNFR1 in vivo; (iv) in murine CM, low doses of TNF seem to protect from CM, whereas excess TNF induces CM and anti-TNF therapies (antibodies, pentoxifylline) did not show any efficiency in protection from CM. Moreover, the involvement of lymphotoxin a, which shares with TNF the same receptors with similar affinity, appears to be an interesting target for further investigation.Received 4 December 2002; received after revision 7 February 2003; accepted 14 February 2003     

紫杉醇诱导HeLa细胞凋亡的研究

目的：探讨紫杉醇抑制HeLa细胞生长的机制。方法：经荧光染色、电镜观察细胞形态,DNALadder及流式细胞仪检测凋亡细胞。结果：紫杉醇作用24h经荧光染色细胞呈不均一亮蓝色,作用48h细胞被染成红色,电镜观察可见细胞变小,染色质浓缩并产生凋亡小体,DNALadder未见明显的梯形条带,流式细胞仪检测紫杉醇作用24h细胞凋亡。结论：紫杉醇可诱导细胞凋亡,也可直接杀伤HeLa细胞,而且以后者为主。     

碘伏联合红外线治疗妇产科腹部手术切口脂肪液化21例

目的探讨碘伏联合红外线治疗腹部手术切口脂肪液化疗效。方法观察组于发现脂肪液化后先挤净渗出物,再以碘伏纱块覆盖伤口,同时予以红外线照射40min;观察组常规进行换药治疗。结果观察组切口愈合率、住院时间均较对照组显著提高及缩短。结论碘伏联合红外线治疗腹部手术切口脂肪液化经济、有效、痛苦小。     

低功率HIFU辐照离体牛肝后强回声出现的原因

目的 研究低功率高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)辐照离体牛肝组织后即刻B超声像图中强回声出现的原因.方法 磁共振(Magnetic Resonance Imaging,MRI)引导的HIFU在50W声功率下分别辐照脱气后的离体牛肝组织10s,20 s,30 s…90 s(实际辐照时间),采用辐照10 s停1 s的方式.在辐照过程中,使用MRI的GRE_TMap序列采集HIFU焦域处的温度,并使用被动空化检测( Passive Cavitation Detection,PCD)系统采集来自焦域的声信号,在LabVIEW开发平台上编程对该信号进行快速傅里叶变换得到其频谱,以判断是否出现空化特征信号.辐照结束后,特离体牛肝组织切成1～2 mm厚的薄片,找到凝固性坏死的最大面,置于加热至37℃的TTC(2,3,5 -氯化三苯基四氮唑)染色剂中染色2min后取出照相.结果 HIFU以辐照10s停1s的方式辐照离体牛肝组织9次后B超声像图中出现强回声,焦域处的温度升高至89.46±2.48℃,PCD系统所采信号的频 谱中未见空化特征信号.切开并染色后的离体牛肝组织在第2次10s的辐照后就有凝固性坏死出现.结论 未达空化阈值的低功率HIFU照离体牛肝组织后即刻B超声像图中强回声出现的原因是焦域处产生的沸腾泡.