Lamotrigine add-on therapy to venlafaxine treatment in adolescent-onset bipolar II disorder: a case report covering an 8-month observation period.

Observations made with lamotrigine add-on therapy with venlafaxine in this case give clues for some aspects of its use in adolescent-onset bipolar II disorder. An 18-year-old adolescent boy with a 3-year history of bipolar II disorder had experienced 2 episodes of hypomania and 4 episodes of major depression. He had been depressed for the last 3 months and had taken olanzapine 5 mg daily for over 6 weeks as mood stabilizer but was still depressed at referral. Other aspects of the patient history included anhedonia, psychomotor retardation, poor concentration, a feeling of hopelessness, hypersomnia, overeating, weight gain, low energy and a refusal to attend school. Parents reported that his symptoms had recently become more severe. His medicine was replaced by venlafaxine, which has a more rapid onset of action and is often used in bipolar depression, especially in patients with atypical depression. Since the clinical response at 6 weeks was only partial, lamotrigine was added to this regimen. The patient responded to lamotrigine after 3 weeks of treatment while on a dose of 50 mg/ day. After 6 weeks of treatment, whilst on a dose of 75 mg/day, his symptoms remitted completely with no evidence of any adverse effects. At the time of publication of this article, the patient had remained euthymic for a total of 8 months. The present report shows that lamotrigine add-on therapy with venlafaxine facilitated clinical remission and that this combination is well tolerated.

Three-dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand.

Many proteins exhibit a large-scale movement of rigid globular domains. Among these, bacterial periplasmic binding proteins involved in substrate transport, or transport and chemotaxis, can be used as prototypes for understanding the mechanism of the movement. Such movements have been found to be associated with specific functions, such as substrate binding, catalysis, and recognition by other biomolecules. We have determined the three-dimensional structures of the lysine/arginine/ornithine-binding protein (LAO) from Salmonella typhimurium with and without lysine by x-ray crystallographic methods at 1.8- and 1.9-A resolution, respectively. The structures are composed of two lobes held together by two short connecting strands. The two lobes are far apart in the unliganded structure, but in contact with each other in the lysine-liganded structure. The large movement of the lobes is a consequence of a 52 degrees rotation of a single backbone torsion angle in the first connecting strand and of distributed smaller changes of three backbone torsion angles of the second connecting strand. The absence of contact between the lysine and the connecting strands suggests that the ligand does not induce the conformational change directly. We instead propose that the unliganded protein undergoes a dynamic change between an "open" and a "closed" conformation and that the role of the ligand is to stabilize the closed conformation. We discuss the nature of a surface area which might be recognized by the membrane-bound complex of these amino acids transport systems.

Crystallization and preliminary X-ray studies of the liganded lysine, arginine, ornithine-binding protein from Salmonella typhimurium.

The periplasmic binding protein LAO from Salmonella typhimurium, which is involved in lysine, arginine and ornithine transport, has been crystallized together with one of its ligands, arginine (LAO-Arg). Preliminary X-ray diffraction studies of LAO-Arg crystal show that it belongs to the orthorhombic space group P2(1)2(1)2(1) and has the unit cell dimensions of a = 37.65 A, b = 59.45 A, c = 115.91 A. Crystals of the LAO-Arg complex diffract beyond 2.0 A resolution.

Crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella typhimurium at 2.7-A resolution.

A wide variety of sugars, amino acids, peptides, and inorganic ions are transported into bacteria by periplasmic transport systems consisting of substrate-specific receptors (binding proteins) and membrane-bound protein complexes. The crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) at 2.7-A resolution shows that the molecule has a bi-lobal structure and that its topological structure is different from other amino acid-binding proteins but is similar to the sulfate-binding protein and maltose-binding protein. High sequence homology between LAO and the histidine-binding protein (HisJ) and the fact that LAO and HisJ share the same membrane-bound protein complex allow one to define functional regions responsible for the ligand binding and for the interaction with the membrane complex.

Crystallization and preliminary X-ray studies of HisJ and LAO periplasmic proteins from Salmonella typhimurium.

Two periplasmic binding proteins, HisJ and LAO, which are involved in histidine and arginine transport, respectively, have been crystallized. Preliminary X-ray diffraction studies of the HisJ and LAO crystals show that both belong to the orthorhombic space group P2(1)2(1)2(1) and have unit cell dimensions of a = 39.26 A, b = 66.17 A, c = 88.33 A and a = 36.08 A, b = 78.34 A, c = 102.02 A, respectively. Both HisJ and LAO crystals diffract beyond 2.0 A resolution.