Lithium citrate for Canavan disease

Current evidence suggests that the effects of lithium on metabolic and signaling pathways in the brain may vary depending on the specific clinical condition or disease model. For example, lithium increases levels of cerebral N-acetyl aspartate in patients with bipolar disorder but does not appear to affect N-acetyl aspartate levels in normal human subjects. Conversely, lithium significantly decreases whole-brain levels of N-acetyl aspartate in a rat genetic model of Canavan disease in which cerebral N-acetyl aspartate is chronically elevated. While N-acetyl aspartate is a commonly used surrogate marker for neuronal density and correlates with neuronal viability, grossly elevated whole-brain levels of N-acetyl aspartate in Canavan disease are associated with dysmyelination and mental retardation. This report describes the first clinical application of lithium in a human subject with Canavan disease. Spectroscopic and clinical changes were observed over the time period in which lithium was administered, which reversed during a 2-week wash-out period after withdrawal of lithium. This investigation reports decreased N-acetyl aspartate levels in the brain regions tested and magnetic resonance spectroscopic values that are more characteristic of normal development and myelination, suggesting that a larger, controlled trial of lithium may be warranted as supportive therapy for Canavan disease by decreasing abnormally elevated N-acetyl aspartate.     

Retinopathy of prematurity in VLBW and extreme LBW babies

Objective : This is a hospital-based, prospective clinical study to determine the incidence, risk factors, and outcome of extreme low birth weight and very low birth weight pre-term babies with retinopathy of prematurity (ROP) at the Sultan Qaboos University Hospital, Oman.Methods : All babies with a birth weight=/ <1500 g and gestational age =/ < 32 weeks admitted in the Neonatal Unit, were screened for ROP between 4 to 6 weeks of age and staged according to the international classification and were followed up until complete vascularization of the retina. Fifty nine babies formed the study group.Results : The overall incidence of ROP was 25.4% (15 out of 59), of which 6 babies had severe ROP and underwent cryotherapy/laser. All babies with ROP had a birth weight <1250 g and were born before 31 weeks of gestation.Conclusion: ROP is a multifactorial disease, the immature retina of the pre-term baby being the primary factor. Incidence and severity was inversely proportional to birth weight and gestational age. Multiple logistic regression analysis showed that sepsis and total parenteral nutrition to be highly significant risk factors. Repeated blood transfusions, hypotension and congenital heart disease with left to right shunt were seen to be considerably associated with the development of ROP. A decrease in overall incidence and severity of ROP was observed in this study.     

An attempt to modulate the microporous diffusion of a model polypeptide by altering its secondary structure

The purpose of the present study was to determine whether intentional alteration of the secondary structure of a model polypeptide, conantokin-G, influenced the rate and extent of aqueous pore diffusion across a synthetic microporous membrane. Use of a microporous synthetic membrane allowed for analysis of polypeptide transport without the confounding variables of protein binding, acid- and/or enzyme-mediated degradation, endocytotic uptake, and enzymatic inactivation associated with a biological membrane. Conantokin-G was intentionally changed from its native random coil structure to the alpha-helix structure using calcium, and both structures were verified using circular dichroism. The alpha-helix structure of conantokin-G was retained even after additional free calcium was removed by equilibrium dialysis. Over the concentration range of 1.25 to 20 mM, there was a linear relationship between the solution calcium concentration and the percent of the alpha-helix conformer present. The apparent permeability, the apparent aqueous diffusion coefficient with and without inclusion of the Renkin function, and the hydrodynamic radii estimated by diffusion and a computer-software program were calculated for the random coil and alpha-helix structures of conantokin-G. Calcium-mediated conversion of conantokin-G to its alpha-helix structure did not significantly (p >.05) change its apparent permeability across a microporous membrane. It is suggested that perhaps complete conversion to the alpha-helix structure of only a fraction of the conantokin-G molecules (only 0.45 or 45% of the molecules can be converted to the alpha-helix structure at Ca(2+) concentrations >or= 20 mM) may have limited the extent of transport of the alpha-helix conformer.     

Fiber orientation and cell-cell coupling influence ventricular fibrillation dynamics

Cell Coupling Influences VF Dynamics. INTRODUCTION: The structure of ventricular fibrillation (VF) is influenced by regional differences in action potential durations and perhaps restitution kinetics and fiber anisotropy. The spatial organization of VF was investigated by measuring the cross-correlation (CC) and mutual information (MI) of membrane potential (Vm) oscillations recorded from multiple sites. METHODS AND RESULTS: Rabbit hearts (n = 6) were retrogradely perfused and stained with di-4-ANEPPS, and VF was elicited by burst pacing. Vm oscillations were recorded optically from multiple locations on the epicardium using a 16 x 16 photodiode array or a 72 x 78 CCD camera. The spatial organization of VF was investigated by calculating the maximum CC (CCmax) and MI (MImax) that can be obtained between any two sites. CCmax and MImax were extended to all pixels and served as indices of the similarities between Vm transients at a reference pixel and all other pixels on the map. We found that maps of CCmax and MImax did not contain discrete regions with high CC or MI. However, CCmax and MImax decreased monotonically with increasing distance between any arbitrarily chosen reference pixel and all other pixels. In VF, maps of CCmax and MImax revealed elliptical gradients of CC and MI that were closely aligned with fiber orientation, with major axis at 127 degrees +/- 8 degrees on the left ventricles. CONCLUSION: CC and MI analysis in fibrillation provides new evidence that anisotropy of fiber orientation and cell-cell coupling have a direct influence on VF dynamics.