The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Experimental study of the efficacy of the endoluminal prosthesis in colonic anastomoses

Colorectal surgery is still associated with a significant morbidity and mortality rate, mostly related to suture failure. We have carried out a randomized experimental study in dogs on colonic anastomoses exposed to a number of anastomotic risk situations. A total of 42 dogs was used. They were divided into three study groups (control, occlusion and diverticulitis), with and without an endoluminal tube. The aim was to assess the efficacy of the endoluminal prosthesis using clinical and radiological assessment of anastomotic healing. Pre- and post-anastomotic intraluminal pressures were also measured to determine whether these might be a factor in suture failure. There were significant differences in suture failure in animals in which the endoluminal tube was used. Mean duration of placement was 10.5 days. In the colon healing study, no significant differences were found between the groups in the pathological examination or in the assay of hydroxyproline content. The presence of the endoluminal tube may increase the maximum pressure applied on the colon wall. No significant differences were found in the intracolonic pressure differentials between the different groups or after the inclusion of the endoluminal prosthesis. The results obtained establish the efficacy of the endoluminal prosthesis in protecting the colonic anastomosis, and could be a valuable technique in colonic anastomoses with a high risk of suture dehiscence.     

Neuroradiological features of intracranial and intraorbital meningeal haemangiopericytomas

The neuroradiological features of six intracranial and one intraorbital haemangiopericytomas (HP) are reviewed. CT was performed before and after IV contrast medium in 5 patients. In 2 patients MRI was performed before and after contrast medium; in another, only unenhanced images were obtained. Five patients were studied by selective external and internal carotid artery angiography. Women constituted 5 of the 7 patients, and the mean age was 50.5 years, thus the sex and age distribution did not differ from that of typical meningiomas. Contrary to previous reports, calcification was present in two of the intracranial HP, and bone erosion was clearly seen in one intracranial HP and the orbital lesion. On MRI the tumours showed no differences from angioblastic meningiomas. All 6 intracranial HP were aggressive; all recurred following treatment and extracerebral metastasis occurred in one case.     

Early stress tests following an uncomplicated myocardial infarct: a comparison between symptom-limited and submaximal tests

To compare the diagnostic and prognostic usefulness of symptom-limited versus load-limited submaximal stress testing, 76 patients, during the first week post acute non-complicated myocardial infarction, were submitted to a symptom-limited Naughton-modified protocol stress test. At 2 METs, 3 METs and maximal effort levels, the tests were classified as positive or negative following the currently used criteria. After a mean follow-up of 15 months, the symptom-limited protocol showed the best sensitivity (95%), specificity (78%), positive (64%) and negative (98%) predictive value, and also the highest risk ratio (27.4) for prediction of subsequent coronary events (2p less than 0.01 vs 2 METs, 3 METs and 2D-Echocardiogram results). Forward stepped multiple correlation analysis indicated independent prognostic value for the results of the symptom-limited stress test (R2: .52 p less than 0.01) and for the location of the myocardial infarction (R2: .05 p less than 0.05) only. In addition, the discriminant prognostic power of the symptom-limited protocol was significant after the fourth month of follow-up (2p less than 0.05 vs submaximal tests and 2D-Echo). Therefore, we recommend the performance of a symptom-limited stress test during the first week post acute non-complicated myocardial infarction, provided that all coronary active medication has been withheld 24 hours before the test.     

Helical computed tomographic angiography in penetrating neck trauma

The purpose of this study was to evaluate the ability of helical computed tomographic angiography (HCTA) to detect vascular injury in penetrating neck trauma. Thirty-five patients (30 gunshot wounds and 5 stab wounds) were studied prospectively with HCTA. Scans were performed with a 5-mm slice thickness at a 1:1 pitch after injection of 90 ml of nonionic contrast medium (30-second delay) at 3 ml/sec. Results were compared with those for angiography (29), surgery (3), ultrasound (2), and local inspection (1). HCTA correctly revealed 19 normal and 10 abnormal studies. In 8 cases, HCTA revealed irregular vessel margins (3), contrast extravasation (2), lack of vascular enhancement (1), and caliber changes (2). In 2 patients, HCTA revealed indirect signs of injury only. In 6 cases, HCTA findings did not correlate with angiography. HCTA detects both direct and indirect signs of vascular injury. Although indirect findings are more sensitive, the direct evaluation of vessels increases the specificity and has a high negative predictive value.     

Retinal detachment in pseudophakia

Retinal detachment in an aphakic eye is a grave therapeutical problem. There exists some fears that cataract extraction with implantation of an artificial lens may increase the number of these complications. Three hundred and seventy cases of cataract extraction with implantation of an artificial lens performed in our department were analysed from the point of view of the incidence of retinal detachment. The cataract was extracted extra- and intracapsularly and the artificial lens was implanted in the anterior as well as in the posterior chamber. During the period of observation--4 months to 3 years--it was established that the number of the retinal detachment in pseudophakia was not larger than in aphakic eyes without implant.     

Cerebrospinal fluid purine metabolites after complex febrile convulsions

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and uric acid were determined in cerebrospinal fluid (CSF) of 15 children after complex febrile seizures (CFS) and in 27 after simple febrile seizures (SFS), and compared with those in a control group of 63 children. There was no statistically significant difference between the groups for any of these metabolites, suggesting that CFS and SFS neither significantly disturb the metabolism of nucleotides, nucleosides or bases nor significantly deplete neuron adenosine triphosphate levels.