Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia

Objective and design

The effects of anesthetics on cytokine release in patients without comorbidities who undergo minor surgery are not well defined. We compared inflammatory cytokine profiles in adult patients undergoing minimally invasive surgery who received isoflurane or propofol anesthesia.

Methods

Thirty-four patients without comorbidities undergoing minor surgery were randomly assigned to receive an inhaled anesthetic (isoflurane; n = 16) or an intravenous anesthetic (propofol; n = 18). Blood samples were drawn before premedication and anesthesia (T1), 120 min after anesthesia induction (T2), and on the first post-operative day (T3). Plasma concentrations of interleukins (IL-) 1β, 6, 8, 10 and 12 and tumor necrosis factor (TNF)-α were measured using flow cytometry.

Results

The pro-inflammatory cytokine IL-6 was increased in the isoflurane group at T2 and T3 compared to T1 (P < 0.01). In the propofol group, IL-6 and IL-8 were significantly increased at T3 compared to T1. However, there were no significant differences in cytokine concentrations between the isoflurane and propofol groups.

Conclusion

An inflammatory response occurred earlier in patients who received an inhaled agent compared with an intravenous anesthetic, but no differences in plasma cytokine profiles were evident between isoflurane and propofol anesthesia in patients without comorbidities undergoing minimally invasive surgeries.     

New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET – [<Superscript>11</Superscript>C]raclopride study

Summary. Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [¹¹C]raclopride binding to striatal D₂ dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10–14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [¹¹C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (−7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D₂ receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D₂ receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D₂ receptors may represent a reinforcing mechanism of drug efficacy. Received October 17, 2001; accepted January 3, 2002 Published online June 28, 2002     

Prognostic significance of pathological and biological factors in hepatocellular carcinoma

Prognostic factors in hepatocellular carcinoma (HCC) conventionally consist of staging with the tumour node metastasis system and grading by tumour cellular differentiation. There are also other factors useful in prognostication but most of them are clinical. With new discoveries in the pathobiology of cancers and introduction of new medical technology, pathological and biological factors of HCC in relation to prognosis have been studied quite extensively. Morphological features of the tumour, both gross and histological, have been found to be significantly related to tumour recurrence and patient survival. Recently, applications of new antibodies and techniques have enabled studies on cellular proliferation using different antibodies such as those for proliferating cell nuclear antigen and Ki-67 protein. These studies on cellular proliferation, as well as assessment of argyrophilic nucleolar organizing regions, have been shown to provide good prognostic significance. Flow cytometric studies on DNA ploidy and studies on expression of genes including the p53 gene, hormone receptors and others show less unanimous results in their prognostic significance. The influence of gender on survival is also reviewed. In conclusion, pathological and biological factors are useful and help to guide clinicians in the management of patients and in assessment of long-term prognosis.     

Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine

We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [18F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p=0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.     

Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies.     

Antimicrobial peptides: synthesis and antibacterial activity of linear and cyclic drosocin and apidaecin 1b analogues

Drosocin and apidaecin Ib are two insect antimicrobial peptides showing a significant sequence homology and a common mechanism of action, which includes stereoselective elements but is devoid of any pore-forming activity. A substantial difference between the two peptides is the presence in the drosocin sequence of an O-glycosylated threonine residue, which is important for its antimicrobial activity. Through the synthesis of a series of differently glycosylated drosocin analogues, we have shown that the antimicrobial activity against several Gram-negative bacteria appears to be modulated by the sugar moiety (Gal vs GalNAc) and the type of glycosidic linkage (alpha-O-, beta-O-, or alpha-C-). The insertion of a glycosylated threonine residue in the apidaecin Ib sequence improves the sequence homology with drosocin but reduces the antimicrobial activity. To gain information on the possible bioactive conformation of these peptides, we synthesized an unglycosylated cyclic analogue of drosocin, containing an intrachain disulfide bond, and the head-to-tail cyclic analogues of drosocin and apidaecin, as well as their corresponding cyclic dimers. Only the large cyclic dimer of apidaecin partially retained the antimicrobial activity, suggesting that a bending of the peptide chain, in particular in the middle of the molecule, is not a structural element characteristic of the bioactive conformation of drosocin and apidaecin. Experiments aimed at testing the effect of selected drosocin and apidaecin peptides on biological membranes showed that some peptides display a moderate hemolytic activity and that a dissociation between antibacterial activity and cytotoxicity to eukaryotic cells can be achieved in differently glycosylated peptide analogues.     

Normal Weight Obese syndrome: role of single nucleotide polymorphism of IL-1 5Ralpha and MTHFR 677C-->T genes in the relationship between body composition and resting metabolic rate

We have identified a subset of metabolically obese, but normal weight individuals, with potentially increased risks of developing the metabolic syndrome, despite their normal body mass index. We determined the relationship among body fat distribution, resting metabolic rate (RMR), total body water amount (%TBW), selected gene polymorphism on interleukin-15 receptor-alpha (IL-15Ralpha) and methylenetetrahydrofolate reductase 677C-->T (MTHFR 677C-->T), to distinguish normal weight obese (NWO) from nonobese with a normal metabolic profile and obese individuals. We analysed anthropometric variables, body composition by Dual energy X-ray Absorptiometry (DXA), RMR by indirect calorimetry, %TBW by bioimpedence analysis (BIA), MTHFR 677C-->T and IL-15Ralpha genotypes of 128 clinically healthy Caucasian individuals. We compared a group of female, defined as NWO and characterised by a BMI < or = 25 kg/m(2) and FM > or = 30% with groups of others female, and males, represented by nonobese with a BMI < or = 25 kg/m(2) and FM < or = 30%, and preobese-obese individuals with BMI > or = 25 kg/m(2) and %FM > or = 30%; none of the males was classified as NWO. Significant correlations were found among body fat mass distribution, metabolic variables, percentage of total body water distribution and selected genetic variations. The variables that contributed significantly to the separation of classes were body tissue (Tissue), %TBW, RMR, the volumes of both oxygen (VO2) and carbon dioxide (VCO2). The distribution of MTHFR 677C-->T and IL-15 genotypes was significantly different between classes. Our data highlight that NWO individuals showed a significant relationship between the decrease in the basal metabolism (RMR), body fat mass increasing and total water amount. Possession of wild type homozygotes genotypes regarding IL-15Ralpha cytokine and 677C-->T MTHFR enzyme characterised NWO individuals.