Tumor necrosis factor-alpha: molecular-biological aspects minireview.

Tumor necrosis factor-alpha (TNF-alpha) a proinflammatory cytokine with multiple actions was first identified for its anticancer activity. However, TNF-alpha has a beneficial function in activation of host defense, its uncontrolled production can lead to pathological consequences. At the cellular level, it is able to exert obviously opposing effects: apoptosis and activation. It modulates survival and activates genes through various intermediates, including protein kinases, protein phosphatases, reactive oxygen intermediates, phospholipases, proteases, sphingomyelinases and transcription factors. In this review, the INF-alpha is characterized at the molecular and cellular level (TNF-alpha mediated signal transduction is discussed in the first part, regulation of its expression in the second one), as well as methods of its determination in biological materials, giving special emphasis to the molecular-biological approach. The full understanding of the molecular mechanism of TNF-alpha will provide the basis for a pharmacological approach intended to inhibit or potentiate selected biological actions of this cytokine.

Effects of sizofiran on endotoxin-enhanced cold ischemia-reperfusion injury of the rat liver.

Kupffer cells (KC), resident macrophages of the liver, have been strongly implicated in lipopolysaccharide (LPS)-induced liver graft injury. However, our recent study showed that sizofiran (schizophyllan glucan) (SPG), which activates KC, did not influence cold ischemia-reperfusion liver injury of LPS-exposed rats. Here we investigated some mechanisms by which SPG does not aggravate LPS-enhanced cold ischemia-reperfusion rat liver injury. Control and SPG-treated rats were exposed to LPS for 2 h prior to hepatectomy. The livers were cold-preserved in University of Wisconsin solution followed by reperfusion with Krebs-Henseleit buffer. We found that SPG dramatically inhibited LPS-induced increases of tumor necrosis factor-alpha (TNF-alpha) in the plasma and bile in vivo. Moreover, LPS-induced TNF- release into the washout solution after cold ischemia was also abrogated by SPG pretreatment. However, SPG increased TNF- release into the perfusate after reperfusion. On the other hand, SPG completely abolished expression of c-myc protooncogene, which is known to sensitize cells to TNF-alpha cytotoxicity. In conclusion, inhibition of both TNF- release after LPS challenge and c-myc expression may explain why activation of KC with SPG does not aggravate endotoxin-enhanced cold ischemia-reperfusion liver injury.

[Carotid-cavernous fistula: clinical and pathological correlations]. / Fistules carotido-caverneuses: corrélation anatomo-clinique.

INTRODUCTION: Depending upon the type of communication between the internal carotid artery and the cavernous sinus, two types of carotid-cavernous fistulae can be distinguished: direct carotid-cavernous fistula (DCCF), for which diagnosis is usually easy because of the obvious signs of orbital congestion, and indirect carotid-cavernous fistula (ICCF) or dural fistula, with few symptoms, associated with a delay in diagnosis which can alter prognosis for function and even life. PURPOSE: The purpose of this study is to determine characteristic signs of both types of CCF and to study their correlation with the anatomical type of vessels involved on the angiogram. The prognosis for both types of fistula was also studied. METHOD: Retrospective single-center study, including patients with angiographically confirmed DCCF or ICCF. Demographic, clinical, and prognostic characteristics of these patients were analyzed and compared with the angiogram findings. RESULTS: Six patients (4 DCCF and 2 ICCF) were included in this study. Mean age at diagnosis was 62.7 years in the DCCF group and 62 years in the ICCF group. Mean time until diagnosis was 7 weeks in the DCCF group and 24 weeks in the ICCF group. Signs of orbital congestion were present in 100% of patients with DCCF and absent in all patients in the ICCF group. Mean proptosis was 3.5mm in the DCCF group and 0.5 in the ICCF group. All patients had an audible bruit on auscultation. The location of the bruit was orbital in all patients with DCCF, and pretragal or jugal in 50% of patients with ICCF. CONCLUSIONS: ICCF can impact mortality and are often underdiagnosed. The diagnostic delay observed in our study reflects the difficulties which persist in recognizing the clinical signs of this condition. ICCF must be suspected in the case of a history suggestive of CCF, even if the clinical examination appears normal. The presence of a bruit must be carefully sought, not only in the classical orbital location, but also in other facial locations as shown in our study. Our results demonstrate that there is indeed a good correlation between the site of the CCF, the location of the bruit, and the vessels involved.

[Dural-cavernous fistulas revealed by bilateral alternating third and sixth nerve palsies]. / Fistule durale carotido-caverneuse révélée par une paralysie bilatérale à bascule des troisièmes et sixièmes nerfs crâniens.

A 74-year-old male was referred for disequilibrium, associated with right third and sixth nerve palsies observed 2weeks after head trauma with no loss of consciousness. On clinical examination, 4months after the injury, contralateral (left) third and sixth nerve palsies were observed, while ocular motility was now normal on the right side. The remainder of the ophthalmological examination was normal. Upon further history, tinnitus was found to have been present since the trauma, and auscultation of the preauricular area demonstrated a systolic bruit. Cerebral angiogram confirmed the presence of bilateral dural-cavernous fistulas. Clinical features of indirect or dural-cavernous fistulas and therapeutic options proposed in the literature are reviewed.

[Chemoembolization of symptomatic bone metastases: technical considerations and therapeutic effectiveness]. / Chimio-embolisation des métastases osseuses symptomatiques : aspects techniques et intérêt thérapeutique.

Chemoembolization of bone metastases is defined by the intraarterial perfusion of a chemotherapy agent followed by microparticles embolization to improve tissue impregnation. This technique increases the local concentration of the chemotherapy agent. Tumor response (stable or reduced tumor size) is achieved in 30-80% of cases with symptomatic relief in over 80% of cases. The indications, technical considerations, and effectiveness of this procedure will be reviewed.

Platelet aggregation in intracranial stents may mimic in-stent restenosis.

We report the case of an early ISR that was due to platelet aggregation despite correct observance of a standard antiplatelet regimen. Biologic testing showed clopidogrel inefficiency, and ISR disappeared on angiography after a loading dose of clopidogrel. This result suggested that the arterial lumen reduction was due to platelet aggregation rather than in-stent myointimal hyperplasia. This observation emphasizes the importance of verifying the efficacy of clopidogrel before placing a stent.

Facial vein catheterization for transvenous embolization of the cavernous sinus. Technique and advantages of the direct jugular vein approach - report of three cases.

SUMMARY: We describe three cases of transvenous embolization of arteriovenous fistulas of the cavernous sinus, achieved through the facial vein approach. The facial vein was catheterized from a jugular vein access. This cervical approach offered good stability to the guiding catheter that permitted us to negotiate difficult curves of the facial vein and to recanalize venous thrombosis in one case.

Orgasmic headache and middle cerebral artery dissection.

A patient with a 20 year history of primary orgasmic headache is described who, after suffering an unusually severe episode of orgasmic headache was found to have a middle cerebral artery dissection. This unusual association of primary and secondary orgasmic headache emphasises the need for a thorough diagnostic examination when the orgasmic headache differs from that of previous episodes or is associated with neurological symptoms.

Marked difference in tumor necrosis factor-alpha expression in warm ischemia- and cold ischemia-reperfusion of the rat liver.

Although tumor necrosis factor-alpha has been implicated in liver injury after both warm ischemia- and cold ischemia-reperfusion, it is unclear whether reactivity of the liver to these stimuli is similar with regard to cytokine expression. Here we compare the effects of warm and cold ischemia on tumor necrosis factor-alpha expression and test the hypothesis that cold ischemia preceding warm ischemia causes overexpression of this cytokine. Rat livers were flushed out with University of Wisconsin solution and subjected to varying periods of warm ischemia, cold ischemia, or cold ischemia plus warm ischemia followed by reperfusion using a blood-free perfusion model. Tumor necrosis factor-alpha and interleukin-10 release into the perfusate and bile were measured by ELISA, and expression of these cytokines and that of c-fos, c-jun, and c-myc were studied by reverse-transcriptase polymerase chain reaction. We found high levels of tumor necrosis factor-alpha in the perfusates of livers subjected to warm ischemia-reperfusion, whereas minimal or no tumor necrosis factor-alpha was detected in livers subjected to cold ischemia-reperfusion or to cold ischemia plus warm ischemia-reperfusion. Reverse-transcriptase polymerase chain reaction confirmed the above findings and showed that immediate early genes were expressed in reperfused groups of livers. Measurements of cytokine release into bile showed that neither tumor necrosis factor-alpha nor interleukin-10 were upregulated by cold ischemia-reperfusion. The results suggest that (1) warm ischemia- and cold ischemia-reperfusion of rat liver lead to very different outcomes with regard to tumor necrosis factor-alpha expression and (2) cold ischemia preceding warm ischemia prevents upregulation of tumor necrosis factor-alpha.