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Biomedical subjects

Z Tomori

Publications and source records attributed to Z Tomori.

At least 19 recordsLinked to original sources

Development of GABA-sensitive spasticity and rigidity in rats after transient spinal cord ischemia: a qualitative and quantitative electrophysiological and histopathological study.

Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor evoked potentials. In addition the effect of intrathecal treatment with baclofen (GABAB receptor agonist; 1 microg), nipecotic acid (GABA uptake inhibitor; 300 microg) and dorsal L2-L5 rhizotomy on spasticity and rigidity was studied. Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized using immunofluorescence and confocal microscopy. At 3-7 days after ischemia an increase in tonic electromyographic activity with a variable degree of rigidity was seen. In animals with modest rigidity a velocity-dependent increase in muscle resistance and corresponding appearance in electromyographic activity (consistent with the presence of spasticity) was measured during ankle rotation (4-612 degrees /s rotation). Measurement of the H-reflex revealed a significant increase in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the same animals a potent increase in motor evoked potential amplitudes was measured and this change correlated positively with the increased H-reflex responses. Spasticity and rigidity were consistently present for a minimum of 3 months after ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and nipecotic acid (GABA uptake inhibitor) provided a significant suppression of spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2-L5 rhizotomy significantly decreased muscle resistance but had no effect on increased amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII. These data demonstrate that brief transient spinal cord ischemia in rat leads to a consistent development of spasticity and rigidity. The lack of significant suppressive effect of dorsal L2-L5 rhizotomy on motor evoked potentials response indicates that descending motor input into alpha-motoneurons is independent on Ia afferent couplings and can independently contribute to increased alpha-motoneuronal excitability. The pharmacology of this effect emphasizes the potent role of GABAergic type B receptors in regulating both the spasticity and rigidity.

Acetyltransferases↗

Sleep apnoea inducing hypoxemia is associated with early signs of carotid atherosclerosis in males.

The intima-media thickness (IMT) of carotid arteries as a marker of preclinical atherosclerosis was measured by ultrasonography in 49 subjects to determine, how strongly the obstructive sleep apnoea (OSA) syndrome is associated with atherosclerosis. Maximal IMT was higher in patients with cardiovascular diseases and with or without risk factors of atherosclerosis, presenting also OSA (apnoea-hypopnoea index=26.1+/-15.6/h) compared to controls without OSA (0.91+/-0.21 mm versus 0.77+/-0.18 mm, p<0.05). The prevalence of IMT > or = 0.85 mm was also higher in patients with cardiovascular pathology presenting OSA than without it (p<0.05). IMT(max) was increased in subjects with mild to moderate OSA alone (AHI=20.4+/-8.7/h) versus healthy controls (0.83+/-0.14 mm versus 0.63+/-0.08 mm, p<0.01). Regression analysis revealed a correlation of IMT(max) with the frequency, intensity and duration of intermittent hypoxemia reflected by AHI (p<0.01), minimal oxygen saturation (p<0.01) and time spent with Sa(O2) < 90% (p<0.05) in patients presenting OSA. The results indicate clear association between early signs of carotid atherosclerosis and moderate OSA in males with and without concomitant cardiovascular pathology.

Adult↗

Interactive measurement and characterization of DNA molecules by analysis of AFM images.

BACKGROUND: In the past few years, computer-based analysis of atomic-force microscopic images has acquired increasing importance for studying biomolecules such as DNA. On the one hand, fully automated methods do not allow analysis of complex shapes; on the other hand, manual methods are usually time consuming and inaccurate. The semiautomated approach presented in this report overcomes the drawbacks of both methods. METHODS: Two kinds of images were analyzed: computer-generated filaments that modeled circular DNA molecules on a surface and real atomic-force microscopic images of DNA molecules adsorbed on an appropriate substrate surface. RESULTS: The algorithm was tested on a group of 140 simulated and 189 real plasmids with a nominal length of 913 nm. The accuracy of the length measurement was statistically evaluated on the ensemble of molecules, with particular attention to the influence of the noise. Mean contour lengths of 912 +/- 5 nm and 910 +/- 47 nm were found for simulated and real plasmids, respectively. The measured end-to-end distance of lambda-DNA molecules as a function of their contour length is reported, from which it is possible to estimate the stiffness of the DNA molecules adsorbed onto a surface; the value obtained for the DNA persistence length (42 +/- 5 nm) is consistent with values measured by other imaging techniques. CONCLUSIONS: An interactive algorithm for DNA molecule measurements based on the detection of the filament ridge line in a digitized image is presented. The simulation of artificial filaments combined with the experimental data demonstrates that the proposed method can be a valuable tool for the DNA contour length evaluation, especially in the case of complex shapes where the use of automatic methods is not possible.

Algorithms↗

Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats.

Experiments were carried out to determine whether there are separate drives from the selected neuronal networks of the brainstem affecting the discharge patterns of laryngeal and respiratory pump muscles during cough. Twenty-four non-decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone were used. Microinjections of kainic acid into the lateral tegmental field of the medulla, medullary midline or pontine respiratory group eliminated the cough evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no effect on them). No pattern of laryngeal muscle activities following lesions resembled the laryngeal cough response. Lesions of the target regions did not result in any apparent changes in the eupnoeic pattern of laryngeal activity. Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine respiratory group seem to be indispensable for the configuration of the central cough motor pattern. However, these neurons do not appear to be essential for the discharge patterns of laryngeal motoneurons during eupnoea. The residual laryngeal "cough" responses are probably mediated by an additional motor drive.

Anesthesia↗

Cough, expiration and aspiration reflexes following kainic acid lesions to the pontine respiratory group in anesthetized cats.

The importance of neurons in the pontine respiratory group for the generation of cough, expiration, and aspiration reflexes was studied on non-decerebrate spontaneously breathing cats under pentobarbitone anesthesia. The dysfunction of neurons in the pontine respiratory group produced by bilateral microinjection of kainic acid (neurotoxin) regularly abolished the cough reflexes evoked by mechanical stimulation of both the tracheobronchial and the laryngopharyngeal mucous membranes and the expiration reflex mechanically induced from the glottis. The aspiration reflex elicited by similar stimulation of the nasopharyngeal region persisted in 73% of tests, however, with a reduced intensity compared to the pre-lesion conditions. The pontine respiratory group seems to be an important source of the facilitatory inputs to the brainstem circuitries that mediate cough, expiration, and aspiration reflexes. Our results indicate the significant role of pons in the multilevel organization of brainstem networks in central integration of the aforementioned reflexes.

Abdominal Muscles↗

Brainstem areas involved in the aspiration reflex: c-Fos study in anesthetized cats.

Expression of the immediate-early gene c-fos, a marker of neuronal activation was employed in adult anesthetized non-decerebrate cats, in order to localize the brainstem neuronal populations functionally related to sniff-like (gasp-like) aspiration reflex (AR). Tissues were immunoprocessed using an antibody raised against amino acids of Fos and the avidin-biotin peroxidase complex method. The level of Fos-like immunoreactivity (FLI) was identified and counted in particular brainstem sections under light microscopy using PC software evaluations in control, unstimulated cats and in cats where the AR was elicited by repeated mechanical stimulation of the nasopharyngeal region. Fourteen brainstem regions with FLI labeling, including thirty-seven nuclei were compared for the number of labeled cells. Compared to the control, a significantly enhanced FLI was determined bilaterally in animals with the AR, at various medullary levels. The areas included the nuclei of the solitary tract (especially the dorsal, interstitial and ventrolateral subnuclei), the ventromedial part of the parvocellular tegmental field (FTL -- lateral nuclei of reticular formation), the lateral reticular nucleus, the ambigual and para-ambigual regions, and the retrofacial nucleus. FLI was also observed in the gigantocellular tegmental field (FTG -- medial nuclei of reticular formation), the spinal trigeminal nucleus, in the medullar raphe nuclei (ncl. raphealis magnus and parvus), and in the medial and lateral vestibular nuclei. Within the pons, a significant FLI was observed bilaterally in the parabrachial nucleus (especially in its lateral subnucleus), the Kolliker-Fuse nucleus, the nucleus coeruleus, within the medial region of brachium conjunctivum, in the ventrolateral part of the pontine FTG and the FTL. Within the mesencephalon a significantly enhanced FLI was found at the central tegmental field (area ventralis tegmenti Tsai), bilaterally. Positive FLI found in columns extending from the caudal medulla oblongata, through the pons up to the mid-mesencephalon suggests that the aspiration reflex is thus co-ordinated by a long loop of medullary-pontine-mesencephalic control circuit rather than by a unique "center".

Anesthesia↗

Activity of the laryngeal abductor and adductor muscles during cough, expiration and aspiration reflexes in cats.

We studied the temporal relationships and the patterns of electromyographic activities of the posterior cricoarytenoid and thyreoarytenoid muscles (laryngeal abductor and adductor), the diaphragm and abdominal muscles in anesthetized cats during mechanically induced tracheobronchial and laryngopharyngeal coughs, expiration and aspiration reflexes. The posterior cricoarytenoid muscle activity reached the maxima just before the peak of diaphragmatic activity in both types of cough and aspiration reflexes and slightly before the top of abdominal muscle activity in coughs and the expiration reflex. Thus, this muscle contributes to the inspiratory phase of coughs and aspiration reflex and also to the expulsive phase of coughs and the expiration reflex. The thyreoarytenoid muscle presented strong discharges in the compressive phase of coughs and expiration reflex (during the rising part of the abdominal muscle activity) and in the subsequent laryngoconstriction (following the diaphragmal and/or abdominal muscle activity) in all four reflexes. This muscle was also slightly activated at the beginning of the aspiration reflex. The existence of four phases of the cough reflex is also discussed.

Abdominal Muscles↗

[Regulation of respiration and its sleep-related disorders].

Four basic control mechanisms of breathing (brainstem respiratory centre, peripheral and central chemoreceptors, intero- and exteroceptive reflexes and suprapontine influences), as well as their sleep-related disorders are analysed. A decrease in central chemoreceptor sensitivity to CO2 and an increase in upper airway resistance during sleep result in hypoventilation and mild hypoxaemia already in physiological conditions. Compensatory increase in ventilatory effort with synchronous inhibition of pharyngeal dilators during sleep reduces the upper airway lumen manifesting with snoring, upper airway resistance syndrome, and OSA. The resulting hypoxaemia may cause marked cardiovascular, neuro-psychic, endocrine-metabolic and behavioural disorders. The augmented ventilatory effort and hypoxaemia evoke reflex dilation of airways and arousal from sleep, stimulating the sympatho-adrenal system, which provokes autoresuscitation by gasping preventing fatal asphyxia. Failure of this autoresuscitation mechanism seems to cause SIDS. Elimination of voluntary breathing by sleep either in Ondine's curse induced by lesions of respiratory centre, or in congenital central hypoventilation syndrome caused by insufficient central chemoreceptors result in respiratory failure and death. Nocturnal attacks of bronchial and cardiac asthma, lung oedema and other consequences of pulmonary congestion are also discussed. The pathomechanism of extreme daytime sleepiness, chronic fatigue, and disorders of memory, cognitive and other brain functions, are also analysed. Severe cardiovascular consequences of SAS may manifest acutely as angina pectoris, myocardial infarction. dysrhythmias, transient ischaemic attacks and even stroke or sudden cardiac death. OSAS may result also in development of hypertension, central obesity, diabetes mellitus, erectile dysfunction, depression, and various behavioural disorders.

Humans↗

Cardiovascular implications of sleep apnea in patients with congestive heart failure.

Recent epidemiologic studies indicate that approximately 40 to 50% of stable patients with congestive heart failure (CHF) suffer from either obstructive sleep apnea (SA) or Cheyne-Stokes respiration with central SA. In either type of sleep apnea, several mechanisms contribute to significant mechanical and adrenergic stresses upon the failing myocardium. These include hypoxemia, reductions in intrathoracic pressure, rises in systemic arterial pressure, increases in left ventricular afterload, and arousals from sleep worsening the sleep architecture. Consequently, sympathetic activation and parasympathetic withdrawal are the hallmark of sleep-related sleeping disorders that contribute to the progression of heart failure and may adversely affect its prognosis. On the other hand, recent studies indicate that successful treatment of either type of SA with continuous positive airway pressure in patients with CHF results in objective and subjective improvement in the severity of heart failure increases in left ventricular ejection fraction, and reductions in sympathetic nervous system activity. Therefore, the early diagnosis and specific treatment of either obstructive or central SA in patients with CHF is highly warranted.

Heart Failure↗

[Nocturnal cardiac dysrhythmias associated with obstructive sleep apnea].

The occurrence of cardiac dysrhythmias have been analysed in 16 adult patients suffering from obstructive sleep apnea syndrome of various severity randomly selected from more than 300 persons examined in our sleep laboratory from 1996 with a complex polysomnography Alice 3 (Healthdyne). The number of apneic episodes emerging in the first, second and third part of sleep was practically the same although their duration prolonged during the night culminating with an average of 25 sec (p < 0.02). OSA episodes caused a decrease of oxyhaemoglobin saturation to lower values during REM compared to NREM sleep (76.1% versus 81.7%, p < 0.05). Cardiac dysrhythmias occurred more frequently during and immediately after, than before OSA episodes demonstrating their causal relations.

Adult↗

[Blood pressure and heart rate monitoring as a method of detection of sleep apnea].

UNLABELLED: Ambulatory blood pressure monitoring (ABPM) and heart rate variability measurement are frequently used by general practitioners for diagnostic of various cardiovascular diseases. Coincidence of hypertension, heart failure and sleep related breathing disorders are very common. Therefore we proposed to use ambulatory blood pressure monitoring device (ABPM), as a tool, for selection of proper patients for polysomnographic examination in sleep laboratory. METHODS: Power spectral analysis of heart rate (HR) monitored together with blood pressure (BP), was performed using a ABPM device (Cardiotens 01, Meditech Budapest) in 24 adults patients. Low frequency/high frequency ratio (LF/HF), which reflects the sympatho-vagal balance, was calculated for the period of sleep versus wakefulness (S/W). Our aim was to detect changes in sympatho-vagal tone during sleep in the following groups of patients: obstructive sleep apnea syndrome (OSAS, respiratory disturbance index RDI = 43.8, arousal index ArI = 17.1), upper airway resistance syndrome (UARS-RDI = 7.4, ArI = 18.3), CPAP treated group (RDI = 6.4, ArI = 8.1) and controls. RESULTS: S/W ratio reflecting sympathetic activation, was lower in controls (0.59), than in patients with OSAS (0.9; p < 0.025) or UARS (2.16, p < 0.01). S/W ratio in patients treated with CPAP (0.68) was similar to controls (p = 0.38). S/W ratio correlated moderately with arousal index (r = 0.94 in group of patients with OSAS). CONCLUSION: S/W ratio reflecting sympathetic activation upon arousal can be used for screening of patient with sleep related breathing disorders, as well as for assessment of CPAP treatment. ABPM with measurement of heart rate variability can detect also effectiveness of antihypertensive treatment with drugs influencing the autonomous nervous system.

Blood Pressure Monitoring, Ambulatory↗

Heat-induced conformational transition of cytochrome c observed by temperature gradient gel electrophoresis at acidic pH.

Temperature-gradient gel electrophoresis (TGGE) has been used to study the thermal unfolding of ferricytochrome c in low and high concentrations of acetic acid. It has been observed that the mobility of cytochrome c is a linear function of temperature when the system is characterized by a homogeneous population of conformation-state, single molecular species. Within the transition temperature range, the mobility clearly displays the characteristic sigmoidal shape describing the transitions of protein unfolding. The data obtained by TGGE were used to estimate the apparent thermodynamic parameters (enthalpy change deltaHvh and transition temperature Tm), associated with the transition of unfolding. The accuracy of the apparent thermodynamic parameters obtained by this method agrees within error limits with the values obtained by direct calorimetric measurements using differential scanning calorimetry (DSC).

Calorimetry, Differential Scanning↗

Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation.

Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials. Such reflex effects include: 1. Pharyngeal dilation as additional treatment in obstructive sleep apnoea. 2. Bronchodilation after deep nasal breathing in asthmatic attacks. 3. Oesophageal sphincter relaxation alleviating gastro-oesophageal reflux. 4. Provocation of sniff- and gasp-like aspiration for reversal of central apnoea. 5. Arousal from sleep increasing the general reactivity. 6. Increase in muscle tone underlying behavioural defence reactions. 7. Increase in sympathetic activity contributing to powerful cardiopulmonary-cerebral resuscitation. 8. Adrenergic reaction mediated by catecholamine secretion.

Arousal↗

STESYS2: extended STESYS software for MS Windows.

The STESYS2 software is a new version of the IBM PC software supporting interactive stereological measurements. In comparison with the previous STESYS, it is enhanced by a number of useful options, e.g. on-line image input via a TV camera coupled with a microscope operating under MS Windows OS. The main advantage, when compared with other such software packages, is the design of the STESYS2 as a module of the freeware image processing system Image Tool which provides a user-friendly environment including a number of image processing and preprocessing routines. Capabilities of the STESYS2 are illustrated by a practical example: estimation of the surface area of capillaries in the terminal villi of human placenta by the Sandau spatial grid method.

Capillaries↗

[Experience with polysomnography in the diagnosis of sleep apnea].

Whole-night recording of 9-30 parameters and calculation of various indices allow differentiation of various sleep related breathing disorders and estimation of their severity (Fig. 1, 2). Parallel monitoring of changes in ventilation, arterial oxygen saturation, ECG, EEG, EMG and others, give a possibility to appreciate the gradual development of cardiovascular, neuropsychic, endocrine-metabolic and other consequences of sleep related breathing disorders, their dependence on different phases and stages of sleep as well as their alterations by treatment.

Humans↗

[Mechanisms in the development of cardiovascular complications in obstructive sleep apnea].

Obstructive sleep apnoea may be accompanied by various cardiovascular consequences resulting from alteration of the activity of the autonomous nervous system. These changes are mediated by: a--hypoxemia developing during the apnoea, b--severe hypoxemia, hypercapnia and acidosis in postapnoea, c--powerful but ineffective ventilatory efforts causing arousal and stimulation of the cardioexcitatory and vasomotor centres. There are four main pathogenetic mechanisms implementing the cardiovascular changes: 1--Functional alteration in the conduction system and the myocardium resulting in nocturnal cardiac dysrhythmias. 2--Vasoconstriction manifesting as angina pectoris, myocardial infarction, brain attacks and pulmonary or systemic hypertension. 3--Pulmonary congestion leading to cardiac or bronchial asthma or even lung oedema. 4--Neuroendocrine activation, including the sympathetic nervous system, renin-angiotensin-aldosterone system, atrial natriuretic peptide and erythropoietin, which may result in nycturia, nocturnal hypotension and diurnal hypertension.

Arrhythmias, Cardiac↗

[Interesting cases of ventilatory therapy of sleep apnea in a group of our patients].

UNLABELLED: In the group of patients investigated in our sleep laboratory and successfully treated by positive pressure applied in to the upper airways through nasal mask (nCPAP) some interesting cases appeared. These cases show beneficial effect of nCPAP therapy, unfortunately not widely spread and recognized in our country. These patients were unsuccessfully treated before by conventional methods, which did not improve their situation for a longer time. Only after polysomnography carried out in our sleep laboratory and after home treatment with nCPAP or BiPAP machine, the situation radically improved. FIRST CASE: In a director of important enterprise after unrelated car accident atrial fibrillation caused by dilation was discovered, which did not respond even on Electro cardioversion. After recognition of severe obstructive sleep apnoea syndrome (OSAS) this patient was treated successfully by BiPAP. The second case: a bus driver, who falls asleep on the traffic light with full buss of passengers. A diagnose OSAS with a multiple sleep latency test result below 2.5 minutes. The nCPAP treatment allowed him to continue to work, but transiently on different position. The third: 40-year-old patient with a body mass index (BMI) 38 and with dysrhythmias IIIb-IVb according to Lown. The respiratory disturbance index (RDI) was 40 and oxygen desaturation bellow 77%. There was bigeminia on ECG. During four hour with nCPAP treatment there was only two randomly ventricular extrasystols appeared, confirming the beneficial effect of treatment. These cases demonstrate a wide spectrum of cardiac dysrhythmias, which have only functional character, but are important for the practice. The demonstrated cases highlighted the importance of home nCPAP therapy in OSAS patients.

Adult↗

Effect of ionic strength on the interfacial properties of cytochrome c.

The surface tension behaviour of oxidised cytochrome c (cyt c) solution was characterised at various pH and ionic strength at the air/water interface. The pendant drop method employing digital image analysis of the drop shape was applied to the measurement of the surface tension. The adsorption properties of cyt c were utilised to study the protein conformation change effected by acidification and ionic strength. At high ionic strength, the saturated steady-state surface tension shows a cooperative change centred around 3.6 induced by a decrease in pH. Using spectroscopic experiments, the apparent pK of the acid-induced transition of horse cyt c from the native to the molten globular state is equal to 3.5. This fact indicates that the saturated steady-state surface tension is a parameter which might be used to monitor conformation changes of cyt c.

Cytochrome c Group↗