Analysis of Mitochondrial Network Morphology in Cultured Myoblasts from Patients with Mitochondrial Disorders.

Mitochondrial morphology was studied in cultivated myoblasts obtained from patients with mitochondrial disorders, including CPEO, MELAS and TMEM70 deficiency. Mitochondrial networks and ultrastructure were visualized by fluorescence microscopy and transmission electron microscopy, respectively. A heterogeneous picture of abnormally sized and shaped mitochondria with fragmentation, shortening, and aberrant cristae, lower density of mitochondria and an increased number of "megamitochondria" were found in patient myoblasts. Morphometric Fiji analyses revealed different mitochondrial network properties in myoblasts from patients and controls. The small number of cultivated myoblasts required for semiautomatic morphometric image analysis makes this tool useful for estimating mitochondrial disturbances in patients with mitochondrial disorders.

[Mitochondrial metabolism in mammalian spermatozoa--a minireview]. / Mitochondriální metabolismus v savcích spermiích--minireview.

Mitochondria are organelles producing macroergic compounds in basically all eukaryotic cells except mature erythrocytes. Mitochondria play an important role even in mammalian spermatozoa, in which mitochondrial ATP biosynthesis covers energetic demands connected with sperm movement (motility), maturation (including capacitation) and oocyte fertilisation. Mitochondrial localization and the existence of some specific mitochondrial-protein isoforms point at its indispensable role in fertility maintenance. Mitochondrial disorders are often manifested in tissues with high-energy demands (myopathy, neuropathy, cardiomyopathy), but mitochondrial dysfunction can be often detected also in other peripheral tissues and cells like spermatozoa. The main goal of this minireview is to summarize the most important findings about mitochondria producing cellular ATP supply and to present spermatozoa as a suitable and valuable biological material, which might be, despite of its uniqueness, a very useful material in clinical diagnostics of certain disorders including mitochondrial or neurodegenerative disorders.

Oligodendroglia from ADSL-deficient patient produce SAICAribotide and SAMP.

Succinylpurines accumulate in the body fluids of patients with adenylosuccinate lyase (ADSL) deficiency but their source in the cerebrospinal fluid remains obscure. Study based on the incorporation of 13C-stable isotope-labeled glycine into cultured oligodendroglia from ADSL-deficient patient and the measurement of labeled products by LC/MS/MS showed total intracellular concentrations of succinylpurines from 45 to 99µmol/l and so these results suggest that these cells can be the source of the compounds in vivo.

The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats.

OBJECTIVE: The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction. METHODS: Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals. RESULTS: Infarcted hearts were characterized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)max, whereas left ventricular end-diastolic pressure (LVEDP), relaxation constant tau and right ventricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVSP in the infarcted hearts. Right ventricular weight significantly increased in rats with infarction; this was attenuated by losartan. Infarct size was not significantly influenced by losartan treatment. Morphometric data revealed decreased capillary supply in infarcted hearts, especially in regions close to infarction; the decrease was less pronounced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm2 to 1471/mm2 in untreated animals but in the treated animals it decreased from 2982/mm2 to only 2037/mm2. Simultaneous significant decrease in myocyte-to-capillary ratio in treated animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP was dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was found. CONCLUSIONS: Decreased ventricular contractility, prolonged relaxation and decreased coronary capillary density in rat experimental cardiac infarction confirm and amplify previous reports dealing with this experimental model. Moreover, we have found evidence of improved hemodynamics and coronary angiogenesis after losartan treatment.