An Improved Method for the Synthesis of the of Indole[2,3-a]Pyrrolo[3,4-c]Carbazole-5,6-Dione N-Glycosides and their Cytotoxic Activity

Pharmaceutical Chemistry Journal - Use of formylindolylacetic acid as a reagent at the stage of preparing the glycosides of bis(indolyl)furan-2,5-diones and dioxane as solvent increased yields from...     

Characteristics of peripheral blood lymphoid subpopulations of shigellosis patients

Chelyabinsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 299–301, March, 1992.     

Effect of single-stranded breaks on ultrastructural organization and cytochemistry of tumor cell chromatin

Laboratory of Chemistry of the Cancer Cell, Latvian Research Institute of Experimental and Clinical Medicine, Ministry of Health of the Latvian SSR, Riga. (Presented by Academician of the Academy of Medical Sciences of the USSR I. B. Zbarskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 11, pp. 591–593, November, 1988.     

The 16189 variant of mitochondrial DNA occurs more frequently in C282Y homozygotes with haemochromatosis than those without iron loading

Background:Patients with hereditary haemochromatosis (HH) are usually homozygous for the C282Y mutation in the HFE gene. They have variable expression of iron overload and present with a variety of complications, including liver disease, diabetes, arthropathy, fatigue, and cardiomyopathy. The mitochondrial 16189 variant is associated with diabetes, dilated cardiomyopathy, and low body fat at birth, and might contribute to genetic predisposition in further multifactorial disorders. The objective of this study was to determine the frequency of the 16189 variant in a range of patients with haemochromatosis, who had mutations in the HFE gene.

Methods:Blood DNA was analysed for the presence of the 16189 variant in British, French, and Australian C282Y homozygotes and controls, with known iron status, and in birth cohorts.

Results:The frequency of the mitochondrial 16189 variant was found to be elevated in individuals with haemochromatosis who were homozygous for the C282Y allele, compared with population controls and with C282Y homozygotes who were asymptomatic (42/292 (14.4%); 102/1186 (8.6%) (p = 0.003); and 2/64 (3.1%) (p = 0.023), respectively).

Conclusions:Iron loading in C282Y homozygotes with HH was exacerbated by the presence of the mitochondrial 16189 variant.

     

Antiangiogenic and antimetastatic properties of Neovastat (Æ-941), an orally active extract derived from cartilage tissue

A novel naturally occurring antiangiogenic agent isolated from cartilage, referred to as Neovastat (AE-941), was examined for its efficacy against tumor neovascularization and progression. Exposure to Neovastat results in ex ovo antiangiogenic properties in the chorioallantoid membrane of chicken embryo (71% decrease in the angiogenic index as compared to the basic fibroblast growth factor (bFGF) treated control embryos, P < 0.0001). Oral administration of Neovastat inhibits bFGF-induced angiogenesis in the Matrigel mouse model (87.5% decrease in hemoglobin as compared to the bFGF-treated control implants, P < 0.0001). Neovastat also induces a dose response decrease of lung metastases in the Lewis lung carcinoma model (oral administration; 69.1% of inhibition obtained at the maximal dose of 0.5 ml/day, P < 0.0001). Combined with a sub-optimal dose of cisplatinum (2 mg/kg, i.p.), Neovastat (0.5 ml/day) improved the therapeutic index by increasing the antimetastatic efficacy and by exerting a protective activity against cisplatinum-induced body weight loss and myelosuppression. In summary, our experimental data provide evidence of antiangiogenic and antimetastatic properties of Neovastat, following oral administration.