PVN electrical stimulation prolongs withdrawal latencies and releases oxytocin in cerebrospinal fluid, plasma, and spinal cord tissue in intact and neuropathic rats

We are studying an endogenous, oxytocinergic analgesia system to obtain more information about normal and pathological pain processes. In the recent years, this oxytocinergic system has been shown to be involved in normal and pathological pain suppression. The paraventricular nucleus (PVN) of the hypothalamus is an important source of brain oxytocin (OT). A descending pathway reaching the dorsal horn in the spinal cord was postulated to mediate analgesic effects at the spinal cord level. However, the oxytocin concentration during pain conditions and during PVN electrical stimulation needs to be determined. We designed experiments to measure the OT concentration in cerebrospinal fluid (CSF), plasma, and OT protein in lumbar spinal cord tissue in control and neuropathic rats. Sciatic loose ligature was used as the experimental method to produce neuropathic pain. The main findings were (1) Chronic pain experiments in animals showed that the stimulation of the anterior part of the PVN increased OT concentration and produced analgesia states, as measured by von Frey, cold, and heat plantar tests. (2) Differential effects were produced by electrical stimulation of the anterior or posterior regions of the PVN; electrical stimulation of the anterior part of the PVN enhanced the OT concentration in CSF and plasma, and it also increased OT protein concentrations in the spinal cord tissue; in contrast, the stimulation of the posterior part of the PVN only increased OT concentrations in CSF. These results suggest the participation of an endogenous analgesia system mediated by OT.     

Endogenous growth inhibition of angiogenesis in brain tumors

The growth inhibition of remote metastases by a primary tumor is known as endogenous growth inhibition leading to tumor dormancy. Such a phenotype has not been described in primary malignant gliomas. However, although glioma cells have frequently spread to other parts of the brain at the time of diagnosis, formation of solid secondary tumors is uncommon. We hypothesize that a dormant population of distant glioma cells exist. The purpose of this study was to investigate whether primary gliomas could inhibit secondary tumor formation. Subcutaneous tumors from human gliomas were grown as xenografts in Swiss nude mice. At a tumor size of at least one cm³, the same amount of cells was injected into the contralateral flank or into the right cerebral hemisphere. Control mice without a primary tumor were injected with tumor cells either into the right flank, the right hemisphere, or bilaterally subcutaneously. Only one of 18 human gliomas demonstrated inhibition at the subcutaneous and intracerebral secondary implantation sites. Growth inhibition of the secondary tumors was accompanied by a significant reduction in microvessel density, upregulation of vascular endothelial growth factor mRNA and downregulation of basic fibroblast growth factor mRNA. Therefore, endogenous inhibition of secondary tumors may represent a rare phenotype in malignant glioma.     

Internal validity of inter‐digital web pinching as a model for perceptual diffuse noxious inhibitory controls‐induced hypoalgesia in healthy humans

Hot and ice‐water immersions are commonly used for heterotopic noxious counter‐stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter‐digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender‐matched drug‐free volunteers aged 21–54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind‐up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2min duration. Wind‐up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5mm thermode) or ballistic impact stimuli (0.5g at 9m/s) on the phalanges of the non‐dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS‐related hypoalgesia. Regardless of pain modality, wind‐up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS‐related and DNIC‐like hypoalgesia. IWP proved its validity for DNIC induction, being practically non‐confounded by BRS.     

Ultrastructural Changes and Glutathione Depletion in the Skeletal Muscle Induced by Protein Malnutrition

Ultrastructural changes and glutathione level were investigated in the pectoralis muscle of rats fed a low-protein diet. Electron microscopy demonstrated the ultrastructural changes of occasional myofibrils affected with protein deficiency that were characterized with the streaming and/ or disruption of the Z-line and disintegration of sarcomeric striation. In the affected sarcomeres, sarcomere length was often elongated and fragmented thick filaments were present together with dense amorphous materials flowing from the damaged Z-line. Glutathione level of muscle in the low-protein diet group (5%casein) was reduced to about one-third of that in the control diet group (20% casein). The study suggests that depletion of glutathione by protein malnutrition is responsible for inducing myofibrillar damage through the excess leaking of Ca 2+ into the cytosol.     

纳洛酮治疗急性重型颅脑损伤的临床疗效观察

目的 为了观察纳洛酮对重症脑损伤的临床治疗效果。方法 选择GCS5－8分患30例,每天应用纳洛酮4．8mg克;随机以30例同等伤情、常规治疗病例作为对照。比较观察意识觉醒、血液流变学及临床征象。结果 纳洛酮治疗后,病人觉醒天数缩短,外伤后脑血管痉挛发生率、血液粘滞度降低,伤残率减少。结论 纳洛酮对于内源性阿片肽引起的生理功能的应激性疾病起效快,作用可靠,其使用中未见有毒副作用。     

Standardisation of thrombin generation test - which reference plasma for TGT?: An international multicentre study

We have previously shown that standardisation and normalization of results improve the intercentre variability of the calibrated automated thrombin generation test (TGT). We suspected that the source of reference plasma (RP) might be a contributing factor to variability and compared 5 commercial RP and a RP provided by the NIBSC, in an international, multicentre study. The detailed composition of the 6 tested plasma samples was determined in the Haemostasis Labotatory in Lyon. The lot to lot consistency, intra-assay, inter-assay variability were calculated for all tested plasmas. The RP and 3 plasma samples (a normal control, a hypocoagulable and a hypercoagulable plasmas) were tested over 6 days, in 5 European centres. Results were normalised against each of the tested RP and intercentre variability of results was compared. All laboratories used the same reagents. Before normalization, the inter-centre variability was 19.8 to 27.3%. After normalization, we observed a significantly improved inter-laboratory variation with all tested RP, despite differences between them. These results clearly demonstrate that the inter-centre variability of TGT can be significantly reduced by using a reference plasma normalization, and that certain RP have a better capacity to reduce this variability than others.     

Endogenous endophthalmitis secondary to septic arthritis caused by group A Streptococcus infection: A case report and literature review

Streptococcus pyogenes is a rare pathogen that causes endogenous endophthalmitis (EE). A healthy 58-year-old woman was diagnosed with EE secondary to septic arthritis caused by S. pyogenes. She underwent enucleation after hospitalization for 14 days with appropriate antibiotic cover. A literature search for outcomes of this condition revealed reports on only 10 eyes among 8 cases identified: 8 eyes (80%) developed poor visual outcome and 5 eyes (50%) underwent enucleation. There were no cases with immunocompromise. Our case report and literature review suggest the importance of awareness of the occurrence of S. pyogenes infection in immunocompetent hosts, and thus early diagnosis and aggressive treatment may be required to improve visual outcome.     

Characterization of sugar receptor expression by neoglycoproteins in oral and oropharyngeal squamous cell carcinomas

Recognition of the carbohydrate part of cellular glycoconjugates by sugar receptors like lectins may contribute to biosignaling and interactions between normal and transformed cells. Such recognitions may be essential for establishing phenotypic characteristics in neoplastic cells, including metastasis-associated properties. To evaluate various glycoconjugates in tumor diagnosis and clinical therapy, a panel of 18 biotinylated neoglycoproteins was prepared. This included conjugates of a histochemically inert carrier protein and crucial sugar moieties such as D-glucuronic acid, - and -N-acetyl-galactosamine, -N-acetyl-glucosamine, melibiose, lactose, maltose, cellobiose, mannose, mannose-6-phosphate, fucose, rhamnose, and xylose. In so doing the diazo derivative of the respective p-aminophenyl glycosides was coupled with galactose, (-N-acetyl-galactosamine or -N-acetylglucosamine via an epoxy group-containing aliphatic spacer. Other glycoconjugates used were the proteoglycan heparin and the sulfated fucan fucoidan. Labeling was effected with cyanogen bromide activation and aminoalkylation for specific detection of endogenous sugar receptors, especially lectins. Tissues studied were paraformaldehyde-fixed, paraffin-embedded surgical biopsies from patients with different stages of squamous cell carcinomas (SCCs) of the oral cavity (n = 16) and oropharynx (n = 17), including three lymph node metastases from oropharyngeal primary tumors. Semiquantitative binding differences of probes to tumor stages were evaluated statistically by the Mann-Whitney U-Wilcoxon rank sum W test. Specific binding of a probe to cytoplasmic and nuclear structures was detected with apparent quantitative differences. Overall, the cytoplasmic compartment revealed a higher intensity of histochemical reaction than did nuclear structures, indicating a comparatively higher density of specific carbohydrate receptors. Significant and highly significant two-tailed P values were noted for tissue types and stages of SCCs of the oropharynx but not the oral cavity.