Therapeutic activation of autophagy by combined treatment with rapamycin and trehalose in a mouse MPTP-induced model of Parkinson's disease.

The neuroprotective effect of autophagy activation by rapamycin and trehalose was studied in a mouse model of Parkinson's disease (PD) induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both rapamycin (10 mg/kg/day, 7 days) and trehalose (2% in drinking water, 7 days) increased the expression of LC3-II (a marker of autophagy activation) in the frontal cortex and striatum of normal C57Bl/6J mice, with signs of an additive effect. Autophagy stimulation in the striatum was confirmed by a lysosomal osmotic test.

P-407-induced Mouse Model of Dose-controlled Hyperlipidemia and Atherosclerosis: 25 Years Later.

The poloxamer 407 (P-407) nongenetic, nondiet-induced mouse model of dose-controlled hyperlipidemia and atherosclerosis was first introduced in 1992. Dyslipidemia is produced in C57BL/6 mice of either sex after intraperitoneal administration of P-407 that is a polyether-based nonionic surface active agent. Aortic atherosclerotic lesions begin to form after 1 month of repeated P-407 administration and obtain maximum size, numerical density, and human-like pathological features by 4 months.

A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced hyperlipidaemia.

Objectives: We evaluated the hypolipidaemic effect of mannan Candida albicans serotype A, relative to atorvastatin, in a mouse model of hyperlipidaemia.

Methods: Mannan serotype A was investigated in vitro and in vivo to determine its effects on macrophage proliferation, nitric oxide (NO) production by cultured macrophages, serum and liver lipids, changes in liver morphology and serum chitotriosidase activity and its expression in the liver.

Key Findings: Mannan serotype A stimulates the macrophage proliferation and NO production in murine peritoneal macrophages in vitro.

Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions.

Background: The aims of this study were to evaluate the effect of poloxamer 407 administration on atherogenic serum lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids, as well as the onset of early atherosclerosis, in mice.

Methods: Mice were administered either sterile saline or poloxamer 407 (to induce a dose-controlled hyperlipidemia) for 1 month and then sacrificed at 1, 4 and 10 days after the last dose of poloxamer 407. Systolic and diastolic blood pressure, the activity of a cysteine protease (cathepsin B) in cardiac and liver tissue, and histological/morphological examination of heart and liver specimens was performed for each group of mice at each time point.

Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice.

Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a 'plus-maze' test.

Evaluation of serum procathepsin B, cystatin B and cystatin C as possible biomarkers of ovarian cancer.

Objectives: To evaluate procathepsin B, as well as endogenous inhibitors of cysteine proteases (cystatin B and cystatin C) in biological fluids as possible biomarkers of ovarian cancer. To observe levels of serum procathepsin B in different age groups.

Study Design: The sample (N=27) of women with gynaecological tumours included 18 patients with ovarian cancer (n=18) and 9 patients with benign ovarian tumours (n=9); 72 healthy women were in the control group.

Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development.

Objectives: To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development.

Background: The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population). Search for new biological markers is important for diagnosis and prognosis in eye tumors.

The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.

The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used.

Influence of atorvastatin and carboxymethylated glucan on the serum lipoprotein profile and MMP activity of mice with lipemia induced by poloxamer 407.

The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used.

Influence of atorvastatin on fractional and subfractional composition of serum lipoproteins and MMP activity in mice with Triton WR 1339-induced lipaemia.

Objectives: The effects of atorvastatin on the atherogenic and anti-atherogenic lipoprotein-cholesterol (C-LP) and lipoprotein-triglyceride (TG-LP) fractions and subfractions at the early stage of murine acute hyperlipidaemia, and its pleiotropic anti-inflammatory effects via the activity of matrix metalloproteinases (MMPs) were studied.

Methods: Atorvastatin (75 mg/kg) was administered to ICR mice with acute lipaemia induced by a single injection of Triton WR 1339 (500 mg/kg). A novel small-angle X-ray scattering (SAXS) method was used for the determination of the fractional and subfractional composition of C-LP and TG-LP.

Characterization of the novel chemically modified fungal polysaccharides as the macrophage stimulators.

By means of carboxymethylation, a novel water-soluble carboxymethyl chitin-glucan (CM-CG) was prepared from the mycelium of Aspergillus niger, and its ability to stimulate macrophages was assessed and compared to that of the previously studied carboxymethylated glucan (CMG) from the yeast Saccharomyces cerevisiae. It was demonstrated that single intraperitoneal (i.p.

Regulation of activity of cathepsins B, L, and D in murine lymphosarcoma model at a combined treatment with cyclophosphamide and yeast polysaccharide.

Changes in the activity of cysteine (cathepsins B and L) and aspartyl (cathepsin D) proteases were investigated at the development of susceptible and resistant variants of murine lymphosarcoma (LS). It has been demonstrated that the variant resistant to the cyclophosphamide treatment is characterized by a lower activity of all three cathepsins in the tumor tissue. Application of a higher dose of cyclophosphamide led to a more pronounced increase of the studied enzymatic activity in mice with a resistant variant of LS, than in those with a susceptible one.

Increased efficiency of Lewis lung carcinoma chemotherapy with a macrophage stimulator--yeast carboxymethyl glucan.

The efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was affected by administration of the water-soluble yeast polysaccharide derivative--carboxymethylated (1 --> 3)-beta-D-glucan (CMG)-a well-known macrophage stimulator. It was found that while cyclophosphamide showed 57% growth inhibition of the intramuscular tumor implants in comparison with the control group, its combined administration with CMG led to 75-90% inhibition. Similarly, increased inhibition of occurrence of lung metastases (up to 92-94%) was observed using the combined application of the two compounds.