The influence of pre-emptive analgesia on postoperative analgesia and its objective evaluation

Introduction

The evaluation of pain intensity is still a subject of research. Mostly psychological evaluations are used. We started to conduct biochemical evaluation in animal experiments. Now we present biochemical evaluation in postoperative pain in man.

Material and methods

In 67 patients herniotomy was done. For pre-emptive analgesia morphine and pethidine were used and the following indicators were measured: visual analogue scale (VAS), measurement of lipid spectra, saccharides and proteins, thioredoxin, super-oxide dismutase (SOD), glutathione peroxidase (GPx) and NAD(P)H-oxidase (NOX), and free radicals using electron paramagnetic resonance (EPR). Blood samples were taken and tested: before pre-medication and intervention, 4 h after and 24 h after intervention.

Results

Free radicals (FR) increased in individual samples during the postoperative course in pethidine and without pre-medication. After application of morphine the FR were insignificantly reduced. Statistically significant differences were found in albumin, prealbumin, apolipoprotein A, total cholesterol, atherosclerotic index, CRP, glucose, and thioredoxin (p ≤ 0.001). A greater difference was seen in VAS values between morphine and pethidine premedications (p ≤ 0.001).

Conclusions

It was proved that the biochemical markers of lipid, protein and saccharide metabolisms and free radicals as well as singlet oxygen can serve as very good indicators of the intensity of pain and nociception. In patients it was proved that pre-emptive analgesia plays an important role in reducing the intensity of postoperative pain. From the three modalities of pre-emptive analgesia morphine represents the best solution.     

Cellular and humoral immune responses to chimeric EGFP-pseudocapsids derived from the mouse polyomavirus after their intranasal administration

Mouse polyomavirus (MPyV) VP1-pseudocapsids carrying enhanced green fluorescent protein (EGFP-VLPs) were used for intranasal immunization of mice. EGFP-VLPs induced strong anti-VP1 but not anti-EGFP antibody production. In vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells (BMDCs) induced remarkable T-cell proliferative response specific for both VP1 and EGFP antigen and IL-2 and IFN-gamma production. Surprisingly, no specific cytotoxic activities against VP1 and EGFP proteins were detected. After intranasal administration of EGFP-VLPs, as well as after polyomavirus infection, a moderate reduction of CD4(+)CD25(+)Foxp3(+) T cells was observed in spleens but not in lymph nodes and peripheral blood, suggesting that both MPyV virions and pseudocapsids are able to induce changes in distribution of regulatory T cells. Treatment of EGFP-VLPs pulsed BMDCs with inhibitors of endosomal acidification proved that presentation of peptides on MHCgp class II is dependent on acidic endosomal environment. Substantial decrease of CD4-specific T-cell proliferation in the presence of proteasome inhibitor suggests that MHCgp class II might load VPL-derived peptides processed by proteasomes. Thus, polyomavirus derived VLPs appear to be promising delivery and adjuvant vehicles for therapeutic proteins.     

Dynamics of T‐cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T‐cells

The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor‐infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease. The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (Stages III–IV), we detected a dominant population of Helios⁺ activated regulatory T cells (Tregs) along with high numbers of monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor‐infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor‐infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNγ. Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.     

Diagnostic utility of neurofilament markers for MND is limited in restricted disease phenotype and for differentiation from compressive myeloradiculopathies

Journal of Neurology - Misdiagnosis is frequent in early motor neuron disease (MND), typically compressive radiculopathy, or in patients with restricted MND phenotype. In this retrospective, single...     

Interference of CD95 expression on human lymphocytes

The study presents the exogenous influence of cadmium in comparison with zinc on the apoptosis of human lymphocytes by CD95 expression and its kinetic changes. The salts of both metals were used in final concentrations of 20 microM in cell cultures with whole blood. The duration of cultivation was 18 and 90 hours. The expression of surface antigens was evaluated by flow cytometry with monoclonal antibodies. In cultures of not stimulated cells we found in average 51.54% CD95 positive lymphocytes. The kinetic study of untreated cells showed elevation after 18 hours of cultivation and a very low expression after 90 hours. The CD95 expression on lymphocytes in cell culture with cadmium and zinc was lower after 18 hours of cultivation than in untreated cells. After 90 hours cultivation we found low levels of CD95 expression on cells treated with cadmium and a great individual variability in the number of positive cells upon the influence of zinc.