Roberto Ebensperger

Biological evaluation of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as inhibitors of LPS-induced TNF- alpha secretion

This study describes the effect of novel 6-Arylbenzimidazo[1,2-c]quinazoline derivatives as tumor necrosis factor alpha (TNF-alpha) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-alpha secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo[1,2-c]quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo[1,2-c]quinazoline derivatives may have a potential as anti-inflammatory agents.

Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis.

This study investigated whether long-term administration of isoproterenol (ISO) induces differential expression of angiotensin-converting enzyme (ACE) in lung, plasma, and left ventricle (LV) during development of left ventricular hypertrophy (LVH) and myocardial fibrosis. Male Sprague-Dawley rats (n = 7–9 per group) were treated with isoproterenol (ISO) 5 mg/kg per day for 10 days or saline and examined at 1, 15, and 33 days after the last injection. ISO stimulated the development of left ventricular hypertrophy (LVH); relative LV weight (mg LV 100/body weight), LV protein content, and LV &bgr;-myosin heavy chain levels increased at day 1. LVH regressed at days 15 and 33. ISO also increased myocardial fibrosis (assessed by hydroxyproline content and morphometry) at days 15 and 33. There no were changes in arterial blood pressure. Long-term &bgr;-adrenergic stimulation with ISO increased ACE expression in lung, LV, and plasma during development of LVH and myocardial fibrosis. However, time courses were markedly different. ISO stimulated a sustained increase in lung and plasma ACE activities, whereas ISO induced a high LV ACE. Plasma ACE activity paralleled lung ACE activity. LV ACE activity correlated with ACE mRNA levels and paralleled development of LVH. Our data suggest long-term &bgr;-adrenergic stimulation induced a differential temporal expression of LV, lung, and plasma ACE in rat during development of LVH and myocardial fibrosis.

Local mechanical response of cells to the controlled rotation of magnetic nanorods

The mechanical response of the cytoplasm was investigated by the intracellular implantation of magnetic nanorods and exposure to low-frequency rotatory magnetic fields. Nanorods (Pt-Ni, ∼200 nm diameter) fabricated by electrodeposition in templates of porous alumina with lengths of approximately 2 and 5 µm were inserted into NIH/3T3 fibroblasts and manipulated with a rotational magnetic field. Nanorod rotation was observed only for torques greater than 3.0 × 10(-16) Nm, suggesting a Bingham-type behavior of the cytoplasm. Higher torques produced considerable deformation of the intracellular material. The cell nucleus and cell membrane were significantly deformed by nanorods actuated by 4.5 × 10(-15) Nm torques. Our results demonstrate that nanorods under magnetic fields are an effective tool to mechanically probe the intracellular environment. We envision that our findings may contribute to the noninvasive and direct mechanical characterization of the cytoplasm.

1-BENZOYL-2-(2-NITROPHENYL)-1H-BENZIMIDAZOLE DERIVATIVES: A NOVEL APPROACH TO THE DEVELOPMENT OF NEW HIV-1 REVERSE TRANSCRIPTASE INHIBITORS

A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229

Glucose effect in the expression of endothelial lipase in human endothelial cells and in patients with diabetes mellitus type 2

INTRODUCTION Endothelial Lipase (EL), enzyme that modulates HDL metabolism, is overregulated by inflammatory-cytokines. Type 2 Diabetes (DM2) has been associated with a subclinical inflammation, so it has been ruled that these patients could have high levels of EL. The objectives of the research are to determine the effect of glucose in the expression of EL in culturing cells and evaluate the relation between the levels of EL and the metabolic control in patients with DM2. METHOD During 24 hours, human endothelial cells (HUVEC) were stimulated with different concentrations of glucose (5.5, 25 and 50 mmol/L), the effect was evaluated over the expression of EL. In DM2 patients levels of EL, glucose and HbA1c were measured. We had a control group (8) to determine the levels of enzyme. EL was measured by immune transference, and the results were expressed by arbitrary units(AU). RESULTS In HUVEC cells, the expression of EL was directly proportional extracellular glucose (p < 0.05). 24 diabetic patients were evaluated (15 females and 9 males) average age from 60 ± 9,7 years old. The studied group showed levels of EL bigger than the control group (14911AU and 10250, 18AU) respectively (p < 0.05). We found no relation between glucose, HbA1c and EL. CONCLUSION In HUVEC cells there is a direct relation between extracell glucose and EL. The diabetic patients had higher levels of EL than the control group, but these was not related with glucose or HbA1c, these shows the existence of other factors that participate in the increasement of EL.