ABSTRACT
Semaphorins and their receptors, plexins, are emerging as key regulators of various aspects of neural and nonneural development. Semaphorin 4D (Sema4D) and B-type plexins demonstrate distinct expression patterns over critical time windows during the development of the murine neocortex. Here, analysis of mice genetically lacking plexin-B1 or plexin-B2 revealed the significance of Sema4D-plexin-B signaling in cortical development. Deficiency of plexin-B2 resulted in abnormal cortical layering and defective migration and differentiation of several subtypes of cortical neurons, including Cajal-Retzius cells, GABAergic interneurons, and principal cells in vivo. In contrast, a lack of plexin-B1 did not impact on cortical development in vivo. In various ex vivo assays on embryonic forebrain, Sema4D enhanced the radial and tangential migration of developing neurons in a plexin-B2-dependent manner. These results suggest that Sema4D-plexin-B2 interactions regulate mechanisms underlying cell specification, differentiation, and migration during corticogenesis.
Subject(s)
Neocortex/embryology , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Receptors, Cell Surface/metabolism , Semaphorins/metabolism , Animals , Cell Movement/genetics , Cell Movement/physiology , Gene Expression Regulation, Developmental , Mice , Mice, Knockout , Mutation/genetics , Mutation/physiology , Neocortex/cytology , Neocortex/metabolism , Nerve Tissue Proteins/genetics , Neurons/cytology , Receptors, Cell Surface/genetics , Sequence Deletion/genetics , Sequence Deletion/physiologyABSTRACT
The role of immune system in development of chronic catarrhal gingivitis in 60 primary patients was defined and substantition of immunocorrection with Licopid in combined treatment was done.
Subject(s)
Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives , Gingivitis/therapy , Immunotherapy , Acetylmuramyl-Alanyl-Isoglutamine/therapeutic use , Adult , Chronic Disease , Combined Modality Therapy , Female , Gingivitis/drug therapy , Humans , Male , Treatment OutcomeABSTRACT
The interrelation between the energy and nitrogenous metabolism of the myocardium during cardioplegia has been studied in patients with congenital valvular heart disease (tetralogy of Fallot--12 patients, ventricular septal defect--5 patients). Whole body hypothermia with repeated heart reperfusion with cold cardioplegic blood perfusate was used for the protection of the myocardium. However, ATP level of the myocardium of some patients decreased by 20% and more of the baseline. This loss was accompanied by a reduction in glutamate and aspartate levels and a rise in ammonium and alanine levels in the myocardium (by 17.7 +/- 3.8; 17.6 +/- 5.9; 61.4 +/- 12.5 and 92.4 +/- 26.3% of the baseline, respectively).
Subject(s)
Heart Arrest, Induced , Myocardium/metabolism , Adenosine Triphosphate/metabolism , Alanine/metabolism , Ammonia/metabolism , Aspartic Acid/metabolism , Glutamates/metabolism , HumansABSTRACT
Two groups of patients subjected to radical correction of Fallot's tetrad and defects of interventricular septum were investigated to ascertain whether the addition of glutamic acid to blood cardioplegic perfusate could improve preservation of myocardial ATP during cardiac arrest. In the control group (17 patients) the myocardial protection was performed by repeated infusions of cold blood potassium cardioplegic solution; in the 2nd group (24 patients) cardioplegic perfusate containing glutamic acid (20 mmol/l) was used. Left ventricular biopsies were taken during the first minute after cross-clamping of the aorta and before the release of the aortic clamp to determine ATP, glutamate and lactate. The cross-clamping time averaged 32 min in both groups. In the patients of the control group the losses of ATP correlated with the decrease in glutamate during the clamping period. A maintenance of a higher myocardial glutamate content by glutamate-containing cardioplegic perfusate prevented ATP fall or increased its level in patients of the 2nd group. There was no significant difference in lactate levels between the two groups by the end of the cardiac arrest. We conclude that enrichment of blood cardioplegic solution by glutamic acid, which may act as a substrate for anaerobic energy production, provides more effective myocardial protection during ischemic heart arrest.
Subject(s)
Adenosine Triphosphate/metabolism , Cardioplegic Solutions/pharmacology , Glutamates/pharmacology , Heart Arrest, Induced , Myocardium/metabolism , Blood , Coronary Circulation , Glutamates/metabolism , Glutamic Acid , Humans , Lactates/metabolism , Lactic Acid , Tetralogy of Fallot/surgeryABSTRACT
Seventeen patients undergoing radical correction of Fallot's tetrad or defects of interventricular septum were investigated. Needle biopsies from the left ventricular apex region were obtained at the 1st min after cross-clamping of the aorta and at the end of cardiac arrest to determine adenosine triphosphate (ATP), glutamate, aspartate, alanine and ammonia. The losses of ATP during clamping period were related to decrease in glutamate. The fall in ATP by more than 20% of the initial level was accompanied by a significant decrease in aspartate, an accumulation of alanine and ammonia in cardiac tissue but did not affect glutamine content. The data obtained prove the participation of specific nitrogenous compounds of human heart, and especially glutamate, in response to energy depletion during ischemia.
