Metabolic Genesis Research Articles

Отравление динитрофенолом в педиатрической практике

Poisoning is one of the main reasons for children entering intensive care units and is associated with a high risk of death in the development of life-threatening conditions. On the example of the clinical case, the features of the course of acute cerebral insufficiency of metabolic genesis in a seventeen-year-old adolescent against the background of enteral administration of dinitrophenol are considered. The main intensive care measures that made it possible to achieve the fastest possible stabilization of the condition are reflected. The algorithm of differential diagnosis of drug-induced liver injury is presented, which can be used in all cases of acute liver failure of unknown origin. Special attention is paid to the need for the earliest possible recognition and targeted pathogenetic treatment of multiple organ dysfunction syndrome. Conclusion. The distinctive feature of this case was the severe course of acute dinitrophenol poisoning in an adolescent with the development of multiple organ dysfunction syndrome, which regressed against the background of the treatment with the patient's complete recovery. Key words: favorable outcome, children, dinitrophenol, intensive care, poisoning

Mutations of mtDNA in some Vascular and Metabolic Diseases

The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus. The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis. The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies. The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.

P 84 Progressive ataxia as leading symptom of chronic neuroborreliosis

Case report A 58-year-old female presented with a slowly progressive ataxic gait disorder for about 6 months. She also reports a recent bladder emptying disorder. Moreover, her husband had observed short-term memory loss with his wife. Her past medical history was uneventful. In clinical examination, an atactic finger-nose test and knee-jaw test as well as stait unsteadiness and atactic gait were impressive. Biceps and brachioradial reflexes could not be attained. There also was a pallhypaesthesia of 3–4/8 at both ankles. Rest of neurological findings was correct, in particular, no paresis, pyramidal path signs, oculomotor or cerebellar signs were found. There was no history of pain. In a cranial MRI, subcortical changes in the white matter as well as laterally symmetrical lesions of the cerebral stem in the lemniscus medialis, along the spinothalamic fibers were observed (Fig. 1a). In an MRI of cervical and thoracic spine, a continuous circular intraspinal enrichment of contrast agent of the pia mater was visible. (Fig. 1b). For the differential diagnosis, an inflammatory DD metabolic genesis was considered. Results of motor evoked potentials indicated a left- and leg-emphasized lesion of central motor tracts to all four limbs. Cerebrospinal fluid (CSF) analysis showed a definite pleocytosis (131 leukocytes/ μ l). In cytological analysis of CSF activated lymphocytes and monocytes were apparent (Fig. 2). Moreover, CSF protein content (386 mg/ dl) was increased; a three-class reaction was found [IgG 77.3 mg/dl (44.9%), IgA 8.86 mg/dl (51.4%), IgM 3.87 mg/dl (74.3%) ]. Furthermore, CSF lactate was increased (4.6 mmol/l). Antibody titers for Borrelia burgdorferi were also clearly increased in CSF (IgG > 1700 U/ml, IgM 2.2 U/ml). Upon repeated questioning, the patient remembered a tick bite more than 12 months previously. Even in retrospect, she had not realized any discomfort (especially pain or cranial nerve dysfunction), except for progressive unsteadiness and gait disorder. In summary, the patient suffers from a neuroborreliosis stage III. Intravenous therapy with ceftriaxone 2 g was administered over 21 days. Discussion The differential diagnosis for ataxia in adults is long and includes, among others, Multiple sclerosis, cerebellar ataxias, neuropathies, vitamin deficiencies, and to the rare Creuzfeldt-Jakob disease ( Bassetti and Mumenthaler, 2012 ). Borreliosis is an infectious disease that passes through several stages and is caused by spirochetes of the species Borrelia. In addition to numerous other symptoms, the nervous system may also be involved. Here, a distinction is made between the acute and the chronic form. While the former primarily presents as meningoencephalitis, a typical manifestation of the chronic form is a spastic-atactic gait, accompanied by a bladder emptying disorder ( Deutsche Gesellschaft fur Neurologie (Hrsg), 2012 ). Chronic neuroborreliosis, with about 2%, is significantly less frequent than acute neuroborreliosis (98%) ( Dersch and Rauer, 2016 ), and thus not the first aspect considered in a differential diagnosis of ataxia. The additionally existing symptoms (bladder emptying disorder, short-term memory disorders) and the conspicuous imaging prompted further evaluation.

Urea Cycle Defects Causing Acute Cerebral Failure in Children: case report

A clinical case, that illustrates the specifics of acute cerebral insufficiency of metabolic genesis due to congenital defects of the urea cycle, is reported. A diagnostics and differential diagnostics algorithm for congenital hyperammonemia is presented and current recommendations for correction of this disease are described. Particular attention is paid to the necessity of the earliest diagnostics possible and targeted pathogenetic treatment.

Effect of induced hypoglycemia on sleep-waking cycle in rats

Relation between sleep disorders and a risk for diabetes has presently been an issue of intensive debate. To unveil neurophysiological mechanisms of interaction between disturbance of sleep-waking cycle (SWC) and blood glucose level it is necessary to ascertain how this change affects SWC. Among other changes in the central nervous system functional state of metabolic genesis it is hypoglycemia that most commonly occurs in diabetes as well as in other diseases. Hypoglycemia is a set of symptoms that as a rule develops within a short time and is characterized by a number of features. One of the pronounced manifestations of hypoglycemia is a paroxysmal fit of drowsiness that differs from a typical pattern of hypoglycemic coma. Experiments were carried out on out bred albino rats. Hypoglycemia was produced by i.p. administration of Humulin, which has a short duration of action and with light deprivation method proposed by us causing more stable hypoglycemia. Blood glucose level was measured in controls and after procedures mentioned above. EEG recordings of SWC were made for 12 h. In the case of blood glucose level reduction obtained by both methods rats rendered more inert and less aggressive. Analysis of 12-h SWC dynamics in hypoglycemic rats has shown: 1. Latency of paradoxical sleep (PS) onset compared to baseline was reduced at the expense of change in the phase distribution – a considerable rise in deep slow-wave sleep (DSWS) and reduction of light slow-wave sleep and wakefulness. 2. Total time of various SWC phases did not alter substantially. However SWC 12-h dynamics was altered. The highest content of DSWS was observed from 9–11 am not followed by PS increase and the highest content of PS (13–15 pm) hypoglycemic hyper-somnia, occurred due to a rise of PS onset. These “peaks” coincided with the least concentration of blood glucose. At this time EEG showed high-amplitude activity. 3. Frequency of PS onset was increased. 4. Amount of self-deprived PS compared to baseline remained unchanged. 5. DSWS fragmentation was considerably reduced. The present findings suggest possibility of using the animals with artificial blood glucose deficit as a model for hypoglycemic states while managing some problems of SWC disorders. Supported by International Science and Technology Center in Moscow Grant G-391.

Metabolic origin of urinary 3-hydroxydicarboxylic acids

3-Hydroxy dicarboxylic acids with chain lengths ranging from 6 to 14 carbons are excreted in human urine. The urinary excretion of these acids is increased in conditions of increased mobilization of fatty acids or inhibited fatty acid oxidation. Similar urinary profiles of 3-hydroxy dicarboxylic acids were also observed in fasting rats. The metabolic genesis of these urinary 3-hydroxy dicarboxylic acids was investigated in vitro with rat liver postmitochondrial and mitochondrial fractions. 3-Hydroxy monocarboxylic acids ranging from 3-hydroxyhexanoic acid to 3-hydroxyhexadecanoic acid were synthesized. In the rat liver postmitochondrial fraction fortified with NADPH, these 3-hydroxy fatty acids with carbon chains equal to or longer than 10 were oxidized to (omega - 1)- and omega-hydroxy metabolites as well as to the corresponding 3-hydroxy dicarboxylic acids. 3-Hydroxyhexanoic (3OHMC6) and 3-hydroxyoctanoic (3OHMC8) acids were not metabolized. Upon the addition of mitochondria together with ATP, CoA, carnitine, and MgCl2, the 3-hydroxy dicarboxylic acids were converted to 3-hydroxyoctanedioic, trans-2-hexenedioic, suberic, and adipic acids. In the urine of children with elevated 3-hydroxy dicarboxylic acid levels, 3OHMC6, 3OHMC8, 3-hydroxydecanoic, 3,10-dihydroxydecanoic, 3,9-dihydroxydecanoic, and 3,11-dihydroxydodecanoic acids were identified. On the basis of these data, we propose that the urinary 3-hydroxy dicarboxylic acids are derived from the omega-oxidation of 3-hydroxy fatty acids and the subsequent beta-oxidation of longer chain 3-hydroxy dicarboxylic acids. These urinary 3-hydroxy dicarboxylic acids are not derived from the beta-oxidation of unsubstituted dicarboxylic acids.

Changes in activity of the histamine and serotonin systems in acute mesenteric vascular obstruction

Experiments on 24 dogs showed that acute occlusion of the cranial mesenteric artery, depending on its duration, leads to biphasic changes in the activity of the histamine and serotonin systems. In the stage of intestinal ischemia the liberation of histamine and serotonin from mast cells is increased, with activation of enzymes responsible for their inactivation (diamine and monoamine oxidases). In the state of intestinal infarction, the enzyme component of the histamine system is considerably inhibited and serotonin activity reduced as the result of progressive intoxication of the animal by substances of microbial and metabolic genesis.