Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

BACKGROUND: INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression. METHODS: Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS. RESULTS: Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group. Limitations: This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies. CONCLUSIONS: INN 00835 appears to be a promising drug for the treatment of major depression.     

Effect of magnesium ions on presynaptic inhibition of monosynaptic reflexes

In experiments on spinal narcotized cats perfusion of lumbosacral spinal cord through central canal with artificial cerebrospinal fluid containing high concentration (20-46 mM) of magnesium ions led to reversible depression of negative DRP as well as to depression of prolonged "presynaptic" inhibition of extensor monosynaptic reflexes produced by repetitive impulse volleys in group I flexor muscle afferents. Magnesium did not cause a depression of monosynaptic reflex discharges in spinal ventral roots.     

Expression and characterization of Gag protein of HIV-1（CN） in Pichia pastoris

To express the core protein of HIV-1 of Chinese prevalent strain （HIV-1 （CN）） in Pichia pastoris, the fulllength gag gene was inserted into the secretory expression vector pHILS1. Linearized recombinant plasmid pHILGAG by Sail was electrotransformed into the yeast strain GS115, and the yeast transformants were identified by PCR. To induce the interest protein to be expressed, the PCR positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS-PAGE, Western blotting and thin layer scanning. mRNA （1.3 kb） was amplified by RT-PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the expressed protein was 55 kD, which was similar to the expected value, and the expressed protein could react with McAb to HIV-1 p24. Thin layer scanning analysis demonstrated that the whole amount of the expressed protein was approximately 13 % of the soluble protein in the supernatant. The recombinant yeast had good genetic stability. The optimal expression conditions of the engineering yeast were as follows： BMMY medium, 80-90% of dissolved oxygen, 1% methanol, and 3-day-cultivation course. Gag proteins were expressed under the optimal expression condition and purified via gel filtration chromatography. The purity of the interest protein was up to 85 %. After the purified proteins were inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice could be detected by Western blotting.     

Adult stem cells and other cancer residents. Part II

In this review, we have attempted to generalize recent data on adult stem cells as the most likely cells, according to the current dominant paradigm, in which a predisposition to malignant degeneration occurs or, in other words, where cancer is initiated.     

Lysosomal cholesterol accumulation: driver on the road to inflammation during atherosclerosis and non‐alcoholic steatohepatitis

Many studies show an association between the accumulation of cholesterol inside lysosomes and the progression towards inflammatory disease states that are closely related to obesity. While in the past, the knowledge regarding lysosomal cholesterol accumulation was limited to its association with plaque severity during atherosclerosis, recently, a growing body of evidence indicates a causal link between lysosomal cholesterol accumulation and inflammation. These findings make lysosomal cholesterol accumulation an important target for intervention in metabolic diseases that are characterized by the presence of an inflammatory response. In this review, we aim to show the importance of cholesterol trapping inside lysosomes to the development of inflammation by focusing upon cardiovascular disease and non‐alcoholic steatohepatitis (NASH) in particular. We summarize current data supporting the hypothesis that lysosomal cholesterol accumulation plays a key role in the development of inflammation during atherosclerosis and NASH. In addition, potential mechanisms by which disturbed lysosomal function can trigger the inflammatory response, the challenges in improving cholesterol trafficking in macrophages and recent successful research directions will be discussed.