Laboratory investigation: Effects of propofol on the systemic inflammatory response during aortic surgery

PURPOSE: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane. METHODS: Twenty young male piglets were anesthetized with either propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed. RESULTS: In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05). CONCLUSION: In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.     

133Granulation Tissue Induction by Lassar Ointment vs. Collagen‐Polyvynilpyrrolidone in Venous Ulcers

Venous leg ulcers derived from tissue destruction is the consequence of a chronic inflammatory process that produces pain and physical disability, diminishing quality of life in patients. In this work, Lassar ointment and lyophilized collagen‐polyvinylpyrrolidone were administered separated each on one half in the same ulcer to 9 patients at the beginning and every 4 days. On day 16, all patients were auto‐grafted with partial thickness skin. Granulation tissue and graft integration were assessed clinically during 3 months. Inflammatory infiltrate, type I and III collagens, elastic fibers, alkaline phosphatase as well as blood vessels were evaluated histologically or histochemically in biopsies taken at the beginning and 16 days after the local treatment. Clinically and morphologically, both treatments demonstrated appropriate granulation tissue promotion and optimal graft integration since the beginning. Nevertheless, in Lassar ointment treated group regionalization of alkaline phosphatase activity was observed, as well as the presence of granuloma in 2 of the 9 patients. In conclusion, Lassar ointment or lyophilized collagen‐polyvinylpyrrolidone are two different promoters of granulation tissue in venous leg ulcers, however Lassar ointment has the capability to produce granuloma and an exacerbated immune response; in consequence, ulcer recidivism could be present, may be due to mineral deposits in the wound.     

Recurrent venous thrombosis following free flap surgery: The role of heparin-induced thrombocytopenia

Complications following free tissue transfer have been well established in the literature. Common and rare causes of free flap failure must be addressed by the treating surgeon when microvascular patency is threatened. With the evolution and prevalence of microsurgery, ‘rare’ causes of free flap failure will become increasingly frequent. A high index of suspicion must be established in patients with multiple failed operative interventions. A case of recurrent free flap failure secondary to heparin-induced thrombocytopenia is presented in a patient with a history of squamous cell carcinoma of the floor of the mouth, and a long-standing history of alcohol and tobacco consumption.     

Mutated recombinant human heavy-chain ferritins and myelosuppression in vitro and in vivo: a link between ferritin ferroxidase activity and biological function.

Human heavy-chain (H-) ferritin muteins obtained by oligonucleotide site-directed mutagenesis, together with wild-type recombinant human H- and light-chain (L-) ferritins, were evaluated for in vitro effects on the suppression of human bone marrow myeloid progenitor cells and for in vivo effects on marrow and splenic myelopoiesis in C3H/HeJ mice. The 10 H-ferritin muteins exhibited alterations of various regions of the molecule, including ones exposed on the outer surface, on the inner cavity, and on the hydrophilic and hydrophobic channels and of the four-alpha-helix bundle forming the subunit structure. They were stable and were electrophoretically analogous to wild-type H-ferritin. The muteins showed in vitro and in vivo myelosuppressive activity analogous to wild type, except for mutein 222, which was totally inactive and which lacked ferroxidase activity. Recombinant human L-ferritin, devoid of ferroxidase activity, was also inactive as a suppressor. The results demonstrate that H-ferritin myelosuppressive and ferroxidase activities are linked. One possibility is that ferroxidase activity may interfere with the cellular uptake of transferrin iron that is needed for cell proliferation, an interpretation consistent with the presently described ability of hemin to overcome H-ferritin suppressive effects.     

Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

The Organization of the Venous Spaces of the Cavernous Sinus

The study of the venous channels in the cavernous sinus in 48 sphenoid bones was performed. Thirty-eight bones were electrolyticly decalcified, subsequently embedded in gelatin, and cut in 1 mm thick slices. Microdissection of the other ten specimens complemented the analysis. Every specimen had the venous structure arranged as a plexus, however, although the channels were variable in number, form, and diameter, the two sides were quite symmetrical. Channels of smaller diameter predominated anteriorly. There was no demonstrable muscular layer in these vessels; the endothelial lining was easily visualized. Fatty tissue separated the venous channels from each other and from arteries and nerves. The distance from the carotid artery and the lateral wall increased anteriorly, but there were significant veins between these two structures in only 35% of the cases. In about one third of specimens the oculomotor nerve was placed over the carotid artery. The abducens nerve was found to be intimately related to the lateral wall without any venous channels between them in 92% of the specimens.