AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice.

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.

Transition from diffusive to subdiffusive motion in colloidal liquids.

In this work we report experimental and theoretical results for the motion of single colloidal particles embedded in complex fluids with different interparticle interactions. The motion of particles is found to follow a similar behavior for the different systems. In particular, the transition from the short-time diffusive motion to the subdiffusive intermediate-time motion is found to occur when the square root of its mean squared displacement is in the order of 1 tenth of the neighbors' interparticle distance, thus following a quantitative criterion similar to Lindemann's criterion for melting.

Hydrodynamic interactions between colloidal particles in a planar pore.

The correlation between the motion of pairs of colloidal particles confined in a planar pore is measured using optical microscopy. The systems studied here are aqueous suspensions of polystyrene spheres of diameter 1.9 µm, interacting as effective hard spheres, confined between two parallel planar plates separated by 2.9 µm. The lateral motion, along the plane parallel to the plates, of the particles is recorded with a time resolution of 30 frames s(-1). From the short-time motion, the hydrodynamic diffusion coefficients are determined as functions of the interparticle distance for various particle concentrations. At low concentrations, when the static correlation between particles is also low, the diffusion coefficients exhibit some symmetry, and at higher concentrations they are modulated by the structure of static correlation.

Colloidal diffusion inside a spherical cell.

The hydrodynamic hindering of a single-particle dynamics under total confinement is measured by optical microscopy. The three-dimensional trajectories of single-colloidal particles confined in spherical water globules of sizes only a few times the particle's diameter are tracked as they sample the entire volume of the globule. The hydrodynamic interactions between the particle and the spherical wall produce a dependence of the short-time diffusion on the particle's distance to the surface and an asymmetry in the radial and tangential components of the local diffusion coefficient, with the diffusion along the tangential direction being faster than along the radial direction. The latter decreasing close to the wall while the former being practically constant.

Correlation between antibody levels in Toxoplasma gondii infected pigs and pathogenicity of the isolated parasite.

Sera and diaphragm muscle tissues were obtained from 109 commercial pigs between September 1991 and May 1992 from the slaughterhouse at La Plata, Provincia Buenos Aires, Argentina. Anti-Toxoplasma gondii IgG antibody reactivity to T. gondii antigens were assayed using sera by indirect immunofluorescence assay and immunoblotting technique. Anti-T. gondii IgG titers at serum dilutions of 1:1024 and higher were noted in 11.0% of the tested sera, and at dilutions of 1:16 and lower in 36.7% of the serum samples. Using mouse inoculation test, T. gondii was isolated from 14 pig diaphragm samples. Of five samples derived from pigs with antibodies at dilutions of 1:1024 and higher, four contained trophozoites which, when inoculated into mice intraperitoneally, killed all recipient hosts within 15 days post inoculation. Parasites detected in seven out of eight samples from pigs with antibodies at serum dilutions of 1:64 and lower formed cysts in the brain, and mice survived longer than 13 days post inoculation. Immunoblotting demonstrated antibody reactivity in pig sera samples with relatively high titers for parasite antigens. Results of the present study suggest that antibody production in infected pigs is apparently dependent on the pathogenicity of the parasite strain.

Clinical characteristics of myocardial infarction following Kawasaki disease: report of 11 cases.

Between 1979 and 1984, 11 patients with myocardial infarction following Kawasaki disease were seen in our hospital. There were seven boys and four girls, aged from 3 months to 6 years. This cardiovascular complication developed in the early stage, from 19 days to 6 months of illness, in all but three patients. Significant clinical symptoms were recognized in only five patients. Two patients died, the conditions of two are well controlled with anticongestive therapy, and the remaining patients are asymptomatic. The diagnosis of myocardial infarction was confirmed by the following clinical findings: typical ECG patterns (10/11), abnormality of the left ventricular wall movement by serial two-dimensional echocardiography (9/10), elevated value of cardiac enzymes (6/6), perfusion defect by thallium 201 myocardial scintigraphy (6/8), and coronary artery occlusion or ventricular aneurysm by angiocardiography (9/9). All patients had markedly dilated and multiple coronary aneurysms during the course of the illness. Because myocardial infarction is frequently associated with the rapidly dilating coronary artery during the acute stage, ECG monitoring, preparation of resuscitation equipment, and use of antithrombotic agents are recommended for those high-risk patients. When a myocardial infarction has been diagnosed, measures including cardiac monitoring, use of vasodilators, inotropic agents, and urokinase may be valuable.

High incidence of aortic regurgitation following Kawasaki disease.

Among 131 patients with Kawasaki disease who underwent cardiac examinations from December 1979 to July 1984, six (4.6%) had aortic regurgitation documented on aortography. A protodiastolic murmur typical of aortic regurgitation was heard in four patients. Both cardiac enlargement on chest roentgenogram and ECG signs of left ventricular hypertrophy were demonstrated in only half of the patients. Of five patients who underwent a second angiographic study 1 year later, two no longer had aortic regurgitation; pulsed Doppled echocardiography at this point revealed aortic regurgitant flow in the remaining three patients. All patients had associated coronary artery aneurysms, and two patients developed subsequent myocardial infarction. The development of aortic regurgitation following Kawasaki disease has been considered to be causally related to the carditis that most frequently occurs during the acute stage of the illness. Our data indicate that aortic regurgitation is not rare but is an important additional cardiovascular complication of Kawasaki disease.