The properties of a proapoptotic 1,4-benzodiazepine, Bz-423, identified through combinatorial chemistry and phenotype screening are described. Bz-423 rapidly generated superoxide (O(2)(-)) in transformed Ramos B cells. This O(2)(-) response originated from mitochondria prior to mitochondrial transmembrane gradient collapse and opening of the permeability transition pore. Bz-423-induced O(2)(-) ...

We have investigated the influences of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) on the efficacy of posaconazole (POS) treatment of acute experimental infections with Trypanosoma cruzi; the standard drug, benznidazole (BZ), was used as a positive control. Wild-type (WT) mice infected with T. cruzi and treated with POS or BZ had no parasitemia, 100% survival, and cure rates of 86 t...

The benzene-benzene (Bz-Bz) interaction is present in several chemical systems and it is known to be crucial in understanding the specificity of important biological phenomena. In this work, we propose a novel Bz-Bz analytical potential energy surface which is fine-tuned on accurate ab initio calculations in order to improve its reliability. Once the Bz-Bz interaction is modeled, an analytical ...

Species ranging from single-cell organisms to social insects can undergo auto-chemotaxis, where the entities move towards a chemo-attractant that they themselves emit. Polymer gels undergoing the self-oscillating Belousov-Zhabotinsky (BZ) reaction exhibit autonomous, periodic pulsations, which produce chemical species collectively referred to as the activator. The diffusion of this activator in...

Drug discrimination was used to examine the effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys. In diazepam-treated (5.6 mg/kg, p.o.) monkeys discriminating the nonselective BZ antagonist flumazenil (0.32 mg/kg, s.c.), the BZ(1)-selective antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) substituted for flumazenil. The onset of action of beta-CCt was d...

A comprehensive theoretical study of the geometries, energetics, and electronic structure of neutral and charged 3d transition metal atoms (M) interacting with benzene molecules (Bz) is carried out using density functional theory and generalized gradient approximation for the exchange-correlation potential. The variation of the metal-benzene distances, dissociation energies, ionization potentia...

One of the most satisfactory pictures for spinning particles is the BarutZanghi (BZ) classical theory for the relativistic extended-like electron, that relates spin to zitterbewegung (zbw). The BZ motion equations constituted the starting point for recent works about spin and electron structure, co-authored by us, which adopted the Clifford algebra language. This language results to be actually...

INTRODUCTION Maximizing responses of malignant gliomas is hampered by resistance to temozolomide (TMZ). Increasing efficacy but not toxicity is a key issue when testing drug combinations. The antimyeloma agent bortezomib (BZ) has shown promising results in vitro and is currently being tested in glioblastoma (GBM) patients. In this study we investigate whether reduction of TMZ dosage is feasible...

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strai...

Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1. The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel achiral anal...