Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia

Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia.The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively.Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6 months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder.The concentration of Trx1 in the patients with first episode of psychosis was 1.5 ± 1.0 ng/ml and 0.8 ± 0.6 ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5 ± 0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p < 0.016 and p < 0.001, respectively).Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.     

Antioxidant and antipyretic properties of methanolic extract of Amaranthus spinosus leaves

ObjectiveMethanolic extract of Amaranthus spinosus (A. spinosus) leaves was screened for antioxidant and antipyretic activities.MethodsAntioxidant activity was measured by 1,1-diphenyl-2-picryl-hydrazile (DPPH) free radical scavenging, superoxide anion radical scavenging, hydroxyl free radical scavenging, nitric oxide radical scavenging, 2,2 '-azinobis-3-ethylbenzothiazole-6-sulfonic acid (ABTS) radical scavenging assays and total phenolic content was also determined. Antipyretic activity of methanolic extract of A. spinosus was measured by yeast induced pyrexia method at concentration of 200 and 400 mg/kg using paracetamol as standard drug.ResultsMethanolic extract of A. spinosus showed potent antioxidant activity. The IC 50 value was (87.50 ±3.52) μg/mL, (98.80±1.40) μg/mL, (106.25±0.20) μg/mL, (88.70±0.62) μg/mL and (147.50±2.61) μg/mL for DPPH, superoxide, hydroxyl, nitric oxide and ABTS radical scavenging activities. Methanolic extract of A. spinosus showed significant (P <0.01) antipyretic activity.     

Measurements of knee rotation-reliability of an external device in vivo

Background

The high mortality of hip fracture patients is well documented, but sex- and cause-specific mortality after hip fracture has not been extensively studied. The purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population.

Methods

Records of 428 consecutive hip fracture patients were collected on a population-basis and data on the general population comprising all Finns 65 years of age or older were collected on a cohort-basis. Cause of death was classified as follows: malignant neoplasms, dementia, circulatory disease, respiratory disease, digestive system disease, and other.

Results

Mean follow-up was 3.7 years (range 0-9 years). Overall 1-year postoperative mortality was 27.3% and mortality after hip fracture at the end of the follow-up was 79.0%. During the follow-up, age-adjusted mortality after hip fracture surgery was higher in men than in women with hazard ratio (HR) 1.55 and 95% confidence interval (95% CI) 1.21-2.00. Among hip surgery patients, the most common causes of death were circulatory diseases, followed by dementia and Alzheimer's disease. After hip fracture, men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease. During the follow-up, all-cause age- and sex-standardized mortality after hip fracture was 3-fold higher than that of the general population and included every cause-of-death category.

Conclusion

During the study period, the risk of mortality in hip fracture patients was 3-fold higher than that in the general population and included every major cause of death.     

Brain inflammation and adult neurogenesis: the dual role of microglia

In the adult mammalian brain, neurogenesis from neural stem/progenitor cells continues in two regions: the subgranular zone in the dentate gyrus and the subventricular zone lining the lateral ventricles. The generated neuroblasts migrate to their appropriate location and differentiate to mature granule cells and olfactory bulb interneurons, respectively. Following injury such as stroke, neuroblasts generated in the subventricular zone migrate also into areas which are not normally neurogenic, e.g. striatum and cerebral cortex. In the initial studies in rodents, brain inflammation and microglia activation were found to be detrimental for the survival of the new hippocampal neurons early after they had been born. The role of inflammation for adult neurogenesis has, however, turned out to be much more complex. Recent experimental evidence indicates that microglia under certain circumstances can be beneficial and support the different steps in neurogenesis, progenitor proliferation, survival, migration, and differentiation. Here we summarize the current knowledge on the role of inflammation and in particular of microglia in adult neurogenesis in the intact and injured mammalian brain. We conclude that microglia activation, as an indicator of inflammation, is not pro- or antineurogenic per se but the net outcome is dependent on the balance between secreted molecules with pro- and antiinflammatory action.     

Prothrombotic effect of prostasomes of metastatic cell and seminal origin

BACKGROUND: Prostasomes are secretory granules produced by the glandular epithelial cells of the prostate. Seminal prostasomes contain high amounts of Tissue Factor (TF) but no studies of TF on malignant cell prostasomes have been made. Here we compare the expression, phosphorylation, and function of TF on prostasomes of different origin. METHODS: TF was detected on prostasomes isolated from seminal fluid and human prostate cancer cell lines (PC-3, DU145, and LNCaP) using FACS and enzyme immunoassay (EIA). Incubation of prostasomes with radioactive ATP under conditions favoring protein kinase A activity led to phosphorylation of TF as detected by immunoprecipitation and SDS-PAGE. The prothrombotic effect of prostasomes was investigated in whole blood and recalcified plasma. Blocking experiments were performed using anti-TF antibodies and corn trypsin inhibitor. RESULTS: TF was expressed on all tested prostasome preparations with lowest values found for seminal ones. Prostasomal TF was the main endogenous substrate for prostasomal protein kinase A. All tested prostasome preparations greatly enhanced the rate of clot formation in a dose-dependent fashion, that is, the clotting capability of prostasomes seemed to be related to the extent of their expression of TF. In addition, the density of the clot varied between different prostasome preparations. When incubated in whole blood, prostasomes were found to associate to WBC thereby inducing them to express and release TF. CONCLUSIONS: These data show that TF is overexpressed and also subjected to phosphorylation by malignant cell prostasomes. This suggests major roles for prostasomes in thrombotic events that occur in some advanced cases of prostate cancer.     

Prothrombotic effects of prostasomes isolated from prostatic cancer cell lines and seminal plasma

Thromboembolism is well recognized as a major complication of cancer. Many tumor cells overexpress tissue factor (TF), which activates blood coagulation in cancer patients. Inflammatory cells expressing TF are also contributors to this activation. In prostate cancer, we believe that prostasomes may also be involved in the initiation of blood coagulation. Prostasomes are submicron secretory granules derived from the prostate gland. They are surrounded by membrane and their extracellular appearance and membrane architecture are complex. Seminal prostasomes are believed to be necessary for successful fertilization and act as protectors of the spermatozoa in the lower and upper female genital tract. Cells from prostate cancer and its metastases are able to produce and export prostasomes to the extracellular environment. These prostasomes may differ quantitatively rather than qualitatively from their normal counterparts with regard to protein composition and function. A majority of human prostate cancers have been found to overexpress TF, and we have demonstrated by various methods that prostasomes derived from prostate cancer cells express considerably higher levels of TF compared with prostasomes of nonmalignant cell origin. The mechanism related to thromboembolic disease generated by prostasomes in prostatic cancer patients may be the early release of prostasomes from prostate cancer cells into the blood circulation, where they will evoke their blood-clotting effects.     

Therapeutic regulation of complement activation in extracorporeal circuits and intravascular treatments with special reference to the alternative pathway amplification loop

A number of clinical treatment modalities involve contact between blood and biomaterials: these include extracorporeal circuits such as hemodialysis, cardiopulmonary bypass, plasmapheresis, and intravascular treatments. Common side effects arising from these treatments are caused by activation of the cascade systems of the blood. Many of these side effects are mediated via the complement system, including thromboinflammatory reactions and rejection of implants. Depending on the composition of the materials, complement activation is triggered via all the activation pathways but is by far mostly driven by the alternative pathway amplification loop. On biomaterial surfaces the alternative pathway amplification is totally unregulated and leads under optimal conditions to deposition of complement fragments, mostly C3b, on the surface leading to a total masking of the underlying surface. In this review, we discuss the mechanism of the complement activation, clinical consequences of the activation, and potential strategies for therapeutic regulation of the activation, using hemodialysis as demonstrator.