Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes

OBJECTIVE: To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM). METHODS: In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint. RESULTS: The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia. CONCLUSIONS: Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells

BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.

Phytochemical and biological study of the aerial parts of lotus lalambensis growing in Saudi Arabia

Phytochemical investigation of the aerial parts of Lotus lalambensis Schweinf resulted in the isolation and identification of 20 known compounds. Liquid-Liquid fractionation of the crude extract followed by chromatographic purification resulted in the isolation of lupeol, beta-sitosterol, oleanolic acid, beta-sitosterol glucoside and stigmasterol glucoside from the petroleum ether fraction. The chloroform fraction afforded heptadecanol, kaempferol [1], kaempferol-3-O-alpha-L-rhamnoside [2], lotaustralin [3], epilotaustralin [4], linamarin [5], kaempferol-3,7-di-O-alpha-L-rhamnopyranoside [kaempferitin] [6] and ethyl-O-beta-D-glucopyranoside [7]. From the ethyl acetate fraction three simple rhamnosyl derivatives; butyl-O-alpha-L-rhamnopyranoside [8] methyl-O-alpha-L-rhamnopyranoside [9] and methyl-O-beta-L-rhamnopyranoside [10] were obtained. Kaempferol-3-0-beta-D-glucopy-ranoside-7-O-alpha-L-rhamnopyranoside [11], kaempferol-3-O-alpha- [beta-D-glucopyranosyl-[1""->2'"]- L-rhamnopyranoside]-7-O-alpha-L-rhamnopyranoside [12], kaempferol-3-O-beta-D-glucopyranoside-7-O-alpha-[beta-D-glucopyranosyl-[1""->2'"]-L-rhamnopyranoside] [13] and the myo-inositol [+] D-pinitol [14] were isolated from the butanol extract. The total extract and different fractions were evaluated for their possible estrogenic, anti-inflammatory and anti-platelets aggregation activities. The chloroform extract showed the highest estrogenic activity, while the petroleum ether was the best in protection against inflammation induced by carrageenan. The strongest inhibition of platelet aggregations was observed with the aqueous fraction

Inositol metabolism in Trypanosoma cruzi: potential target for chemotherapy against Chagas' disease

Chagas' disease is a debilitating and often fatal disease caused by the protozoan parasite Trypanosoma cruzi. The great majority of surface molecules in trypanosomes are either inositol-containing phospholipids or glycoproteins that are anchored into the plasma membrane by glycosylphosphatidylinositol anchors. The polyalcohol myo-inositol is the precursor for the biosynthesis of these molecules. In this brief review, recent findings on some aspects of the molecular and cellular fate of inositol in T. cruzi life cycle are discussed and identified some points that could be targets for the development of parasite-specific therapeutic agents.

Kinetic studies on the membrane form of intestinal alkaline phosphatase

We have purified different membrane and soluble forms of alkaline phosphatase from human placenta and bovine intestine. The enzymes will be used as markers in immunoconjugates and/or as model for membrane enzyme studies. The membrane formof alkaline phosphatase extracted from bovine intestine was purified on Q-Sepharose and on L-histidyldiazobenzylphosphonic acid-agarose columns to remove phosphodiesterase activity. The purified enzyme had a molecular mass of 61 kDa, Km of 1208 µM, and Vmax 240 µmol pNP/min when assayed in 1 M diethanolamine, 0.5 mM MgCl2 buffer, pH 9.8, containing 10 to 2250 µM of pNPP at 37§C. In the present investigation we studied the effect of salts and inositol derivatives on this enzyme activity, which was found to depend on 0.5 mM Mg2+, and to be fully inhibited by 1.2 mM Hg2+. Vanadate (0.5 mM) and Zn2+ (0.5 mM) reduced the Km value by 43 percent and 84 percent, respectively. Inositol (2 mM) and inositol-2-monophosphate (2 mM) reduced the activity by 23 percent and 17 percent. Inositol-1-monophosphate (0.5 mM) and cyclic-inositol-(1:2)-monophosphate (0.5 mM) enhanced their Km value by at least 30 percent compared to p-nitrophenylphosphate