Viral infections in the mouth

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein–Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via non-glossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.     

维生素E琥珀酸酯诱导人胃腺癌细胞凋亡途径

目的　探讨维生素E琥珀酸酯 (VES)诱导人胃腺癌SGC -790 1细胞凋亡的死亡受体 (Fas)信号转导途径。方法　人胃腺癌SGC -790 1细胞经不同剂量VES(5,10 ,2 0 μg/ml)处理 ,同时做琥珀酸、维生素E和空白对照 ,采用DAPI(4,6-贰脒基 -2 -苯基吲哚 )荧光染色法观察细胞凋亡情况 ,用WesternBlot法检测Fas、带有死亡结构域的Fas相关蛋白 (FADD)和天冬氨酸特异性半胱氨酸蛋白酶 (caspase -8)蛋白表达情况 ,Fas和FADD反义寡聚核苷分别转染SGC -790 1细胞后 ,用荧光法检测caspase -8活性。 结果　经VES处理后的细胞DAPI染色可见凋亡的形态学改变 ,2 0 μg/mlVES处理 48h后的细胞凋亡率为 89.6% ;VES处理 48h后Fas、FADD和caspase -8蛋白表达明显增加 ,且呈剂量 -效应关系 ;阻断Fas可明显抑制FADD蛋白表达 ,Fas和FADD反义寡聚核苷转染细胞后caspase -8活性明显降低 (P <0 .0 1) ,其中阻断Fas的效果高于阻断FADD。结论　维生素E琥珀酸酯诱导人胃腺癌SGC -790 1细胞凋亡过程中启动了Fas信号转导途径 ,VES启动Fas后 ,FADD将Fas和caspase -8联接起来 ,活化caspases级联反应 ,从而构成Fas/FADD/caspase -8的凋亡信号途径     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

促渗剂对水合胼胝类脂热转变影响的差示扫描热分析研究

从人胼胝组织提取出类脂经水合后代替人皮肤角质层用作差示扫描热分析研究促渗剂作用的简单模型。研究了１，８－桉油精，月桂氮酮和丙二醇等促渗剂对水合胼胝类脂热转变特征的影响。三种促渗剂均不同程度地降低水合胼胝类脂的热变温度，作用强弱依次为１，８－桉油精＞月桂氮酮＞丙二醇。丙二醇与１，８－桉油精或月桂氮酮混合应用时对热转变的影响具有协同作用。结果提示促渗剂可能改变脂质分子的排列和增加其流动性。同时，水的存在对脂质分子物理结构的形成具有重要作用。     

Œdème cérébral aigu mortel chez un enfant diabétique

A case is reported of fatal acute cerebral oedema occurring in a 15-year-old child suffering diabetic ketoacidosis. He had severe gastro-enteritis, with a weight lose of 8 kg over a period of 8 days (initial weight = 50 kg). He was admitted in a stupor with pH 7.15, 129 mmol.l-1 natraemia, and 31 mmol.l-1 blood glucose concentration. Blood osmolaity was calculated to be 310 mosmol.l-1. He was rehydrated with 416 ml.h-1 normal saline and 416 ml.h-1 of 1.4% sodium bicarbonate. At the same time a total dose of 75 i.u. of ordinary insulin was given. After 2 h, the patient's condition suddenly worsened with unreactive coma, bilateral fixed mydriasis, respiratory pauses, and impairment of haemodynamic state (heart rate 150 b.min-1, blood pressure 80/50 mmHg). The diagnosis of cerebral oedema with severe intracranial hypertension was confirmed by different investigations. Despite ventilatory support and continued intensive care, the patient died a few hours later. It is concluded that some degree of subclinical brain swelling could be common occurrence during diabetic ketoacidosis, present maybe even before the start of treatment. Such cases of cerebral oedema are often reported, but the pathophysiological mechanisms remain unclear. However, unlike this case, rehydration must be moderate (less than 41.m-2.day-1), especially in case of hyponatraemia. Insulin and sodium bicarbonate must be used with care. Early rigorous clinical and biological monitoring is essential. Treatment should aim at a progressive correction of the metabolic disturbances.     

1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A₁ receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A₁ receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA₁ area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects.     

Allergen activates peripheral blood eosinophil nuclear factor-κB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-α and interleukin-8

BACKGROUND: Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen-induced activation of eosinophil NF-kappaB and generation of granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8. METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF-kappaB activation by 10 microg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF-kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot. Cytokine production was assessed both by immuno-staining of eosinophils and by assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral blood eosinophils from atopic, but not non-atopic, donors induced activation of NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha. The activation of authentic NF-kappaB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB. Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF-kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.     

Deep brain stimulation for Parkinson''s disease: electropermeabilization and activation

Deep brain stimulation, DBS, is an accepted technique for the treatment of Parkinson's disease. DBS affects the electrical functions of neurons, but exactly how it alters those functions is not clearly explained. An electrical model is determined to simulate treatment with DBS of the sub thalamic nucleus. This model shows the difference in electrical fields between the inside and the outside the neurons. The generated electrical field near the electrodes is high enough to perform an electropermeabilization of the cell membranes, which most likely blockade normal nerve pulses or reduce the nerve impulse speed. Further away from the electrodes activation of large axons is performed.     

Factors associated with quality of life in Menière's disease

The aim of this study was to identify the factors associated with better or worse quality of life in a sample of people with Menière's disease drawn from a UK self‐help group (the Menière's Society) and to assess the forms of support on which the respondents could draw. A postal survey was sent to 1000 randomly selected group members, containing validated questionnaires assessing: (1) quality of life (the Short Form 36 (SF‐36)); (2) factors that might predict quality of life; and (3) usage of resources provided to members by the Menière's Society. A total of 509 members completed the main survey, and 370 the second part of the survey. Factors associated with a less good quality of life included more severe vertigo, pressure in the ear, hearing loss and tinnitus, being younger, being female, living alone, having a lower occupational status and believing that the attitude of the consultant is unhelpful. Levels of vertigo severity in this sample were similar to those found in hospital samples, but it is possible that these respondents may differ in other respects from patients who do not join a self‐help group.