Effects of tumor necrosis factor-alpha on insulin stimulated amino acid transport in cultured rat hepatocytes

It has been suggested that tumor necrosis factor alpha (TNF-alpha) plays a pivotal role in the pathogenesis of insulin resistance. It could act directly or indirectly in liver. The aim of this study was to determine direct short time (4 h) and long time (24 h) action of TNF-alpha on amino acid transport in cultured rat hepatocytes and possible role of protein kinase C (PKC) in insulin signal pathway and insulin resistance. Hepatocytes were isolated by a modified collagenase perfusion technique and cultured for 24 h in M 199 medium. In the presence of insulin basal alpha-amino isobutyric acid (AIB) uptake was increased 55%. TNF-alpha in short time action did not change basal AIB transport, but significantly (25%) increased insulin stimulated uptake. Short time action of TNF-alpha was ameliorated by phorbol ester treatment. These results indicated that PKC activation is important in insulin signaling and TNF-alpha action. TNF-alpha acting directly did not cause insulin resistance in cultured hepatocytes.     

Mood effects of weather conditions of the Zagreb population, Croatia

The level of information on biometeorologic reports and mood effects of weather conditions on the Zagreb population were assessed in a sample of 782 subjects. Only 103 (13.2%) study subjects had not been informed on biometeorologic reports. Mood effects of weather conditions were reported by more than 76% of study subjects, 18.3% of them reporting meteorosensitivity. Meteorosensitivity showed a female predominance, and increased with age and level of education. 88% of chronic patients reported discomforts caused by changes in atmospheric conditions. Apathy and sleepiness were the most common mood changes associated with weather changes, whereas humid weather was indicated as a weather type that caused most discomforts in study subjects.     

Post-treatment de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma

Background

Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. Dasatinib is commonly used for the treatment of acute lymphoblastic and chronic myelogenous leukemia. Previous clinical studies in melanoma returned inconclusive results and suggested that patients respond highly heterogeneously to dasatinib as single agent or in combination with standard-of-care chemotherapeutic dacarbazine. Reliable biomarkers to predict dasatinib responsiveness in melanoma have not yet been developed.

Results

Here, we collected comprehensive in vitro data from experimentally well-controlled conditions to study the effect of dasatinib, alone and in combination with dacarbazine, on cell proliferation and cell survival. Sixteen treatment conditions, covering therapeutically relevant concentrations ranges of both drugs, were tested in 12 melanoma cell lines with diverse mutational backgrounds. Melanoma cell lines responded heterogeneously and, importantly, dasatinib and dacarbazine did not synergize in suppressing proliferation or inducing cell death. Since dasatinib is a promiscuous kinase inhibitor, possibly affecting multiple disease-relevant pathways, we also determined if basal phospho-protein amounts and treatment-induced changes in phospho-protein levels are indicative of dasatinib responsiveness. We found that treatment-induced de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma.

Conclusions

Loss of p53 phosphorylation might be an interesting candidate for a kinetic marker of dasatinib responsiveness in melanoma, pending more comprehensive validation in future studies.

     

The salt marsh vegetation on the East Adriatic coast

Phytosociological characteristics and a rate of endangerment of the salt marsh vegetation in central and southern parts of the east Adriatic coast were studied. A total of 73 vegetation relevés were made and elaborated according to the standard procedures of the Braun-Blanquet method. Numerical analysis of the relevés and life forms was performed. Two associations of the class Arthrocnemetea-Puccinellio festuciformis-Arthrocnemetum fruticosi and Limonio-Artemisietum coerulescentis were recorded, together with the association Juncetum maritimo-acuti of the class Juncetea maritimi. These associations show no significant differentiation with regard to their floristic composition, but only in terms of particular species cover and frequency rates, as well as by life forms and microecological habitat conditions. These are specific habitats, rarely found in the studied area, and highly threatened by human activity (tourism, agriculture).     

Epidemiology of prostate cancer in the mediterranean population of Croatia--a thirty-three year retrospective study

Prostate cancer is a major public health problem of the male population in all the developed countries. This non-skin cancer is the foremost one facing man today. Prostate cancer has become the second leading cause of cancer death2. In this study we investigated changes in the prostate carcinoma incidence and manifestation during a thirty-three years period. The study included 1226 cases of prostate cancer diagnosed from 1972 to 2005 in the Primorsko-Goranska County, Croatia. The age-adjusted incidence of prostate cancer increased from 1.69 per 100,000 men annually in 1972 to 137.58 per 100,000 men annually in 2005, which is an 81.4-fold increase. The percentage ofpatients with bone metastases on the first medical examination decreased from 1972 (75%) to 2005 (15%). The most of the patients with bone metastases at the first medical examination were between 30 and 50 years old. Early detection measures, such as prostate specific antigen testing and transrectal ultrasound guided prostate biopsy combined with the raised public awareness of the disease, most probably resulted in an increase of incidence.     

Prednisolone neuroprotective therapy in age-related macular degeneration

134 patients with Age-related Macular Degeneration (AMD) (aging 47-75 years) were treated in therapy procedure with parabulbar injections of Methylprednisolone Acetate and Prednisolone Acetate. In the first group of patients with AMD (n = 71 patients) were treated with Methylprednisolone acetate, and second group (n = 63 patients) with Prednisolone acetate. Each patient was given doses of 60 mg, through two weeks, 10 mg every second day. It's estimated in all patients ameliorate in macular threshold, so that it's in the group with Methylprednisolone treatment, ameliorate effect begins after first week, than in second group, treated with Prednisolone, initial ameliorate effect is after second week. Complete effect in both groups is after 2 months. It can be concluded that the treatment of AMD with glucocorticoids has the ameliorate effect in vision loss and it is decided that earlier effect in the group treated with Methylprednisolone, is probably of higher affinity for glucocorticoid receptors.     

Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol

Cancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.Subject terms: Cell biology, Molecular biology, Experimental models of disease