Hulín I

Neurobiology of cancer: Interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain

The interactions between the nervous, endocrine and immune systems are studied intensively. The communication between immune and cancer cells, and multilevel and bi-directional interactions between the nervous and immune systems constitute the basis for a hypothesis assuming that the brain might monitor and modulate the processes associated with the genesis and progression of cancer. The aim of this article is to describe the data supporting this hypothesis.

Neural-endocrine-immune complex in the central modulation of tumorigenesis : Facts, assumptions, and hypotheses

For the precise coordination of systemic functions, the nervous system uses a variety of peripherally and centrally localized receptors, which transmit information from internal and external environments to the central nervous system. Tight interconnections between the immune, nervous, and endocrine systems provide a base for monitoring and consequent modulation of immune system functions by the brain and vice versa. The immune system plays an important role in tumorigenesis. On the basis of rich interconnections between the immune, nervous and endocrine systems, the possibility that the brain may be informed about tumorigenesis is discussed in this review article. Moreover, the eventual modulation of tumorigenesis by central nervous system is also considered. Prospective consequences of the interactions between tumor and brain for diagnosis and therapy of cancer are emphasized.

Signal-averaged ECG in patients with antidepressant therapy

The signal-averaged electrocardiography (SAECG) identifies patients at risk of ventricular arrhythmias and sudden cardiac death. Since the similarity has been known of the pharmacology of class I antiarrhythmics and tricyclic antidepressants, the potential proarrhythmic effects of antidepressants has become a particular problem. The influence of sodium channel blocking antidepressant drugs on the SAECG time-domain parameters was evaluated, using high-pass filters of 25 Hz and 40 Hz. SAECG was performed in 11 depressed patients with normal cardiac status before and for 4 weeks after antidepressant initiation. At the filter setting of 25 Hz, a significant worsening of all studied SAECG parameters (filtered QRS duration, low-amplitude signal duration, root mean square voltage in the first and in the last 40 ms of the filtered QRS) was found in our patient group. Using a 40 Hz high-pass filter, the results were similar. Antidepressant therapy significantly prolonged filtered QRS duration, significantly reduced root mean square voltages in the first and in the last 40 ms of the filtered QRS and non-significantly prolonged low amplitude signal duration. Amitriptyline and maprotiline induced late potentials (LP) in 2 patients at 40 Hz high pass filter setting. No patient had LP at 25-250 Hz. Our pilot study indicates that sodium channel blocking antidepressant drugs may affect SAECG variables similarly to class I antiarrhythmics. SAECG might be useful in categorizing of antidepressant agents and risk stratification of psychiatric patients.

Heart remodeling in the hereditary hypertriglyceridemic rat: effect of captopril and nitric oxide deficiency.

Abstract: Aim—The hereditary hypertriglyceridemic (hHTg) rat is characterized by insulin resistance, hypertension, and hypertriglyceridemia. Thus, we investigated whether (a) remodeling of the heart left ventricle (LV) is present under the given hypertensive situation and (b) whether this potential alteration could be influenced by an inhibition of the angiotensin converting enzyme (ACE) and/or by a blockade of nitric oxide production. Methods—Five groups of rats were investigated: control Wistar (C) rats, hHTg rats, hHTg rats given captopril (100 mg/kg/day) (hHTg + CAP) or NG‐nitro‐l‐arginine methyl ester (L‐NAME, 40 mg/kg/day) (hHTg + L‐NAME), and hHTg rats given the combination of both drugs (hHTg + CAP + L‐NAME) for 28 days. Systolic blood pressure (SBP) was measured by tail‐cuff plethysmography each week. After cervical dislocation, the relative weights of the left and right ventricles (LV/BW, RV/BW) were obtained, the LV nucleic acid concentrations were analyzed, and the fibrosis amount was quantified with aid of a semiquantitative histological technique. Results—In the hHTg group, the increased SBP (141.7 ± 4.4 vs. 117.2 ± 3.1 mmHg in controls) was linked to hypertrophy of the LV (1.63 ± 0.05 vs. 1.30 ± 0.03 g/kg in controls) with only a minimum of fibrosis. DNA concentration in the LV was decreased (0.45 ± 0.03 vs. 0.69 ± 0.04 mg/g w.w. in controls) in the hHTg group. Captopril normalized SBP and decreased the LV/BW (1.44 ± 0.04 g/kg). Chronic administration of L‐NAME to the hHTg rats additionally enhanced (189.3 ± 5.9 mmHg) the already raised SBP, stimulated fibrosis development, and increased DNA concentration (0.54 ± 0.02 mg/g w.w.) in the LV compared to hHTg group, yet without additional weight increase of the LV. The combined treatment of the hHTg rats with CAP and L‐NAME resulted in normal SBP and the development of LV hypertrophy, and fibrosis was substantially reduced. Conclusions—(a) The heart of hHTg rats carries signs of LV hypertrophy with minimal fibrosis. (b) Nevertheless, LV fibrosis was increased in the hHTg + L‐NAME group. (c) Captopril normalized SBP and decreased the extent of LV hypertrophy in both the nontreated hHTg and the hHTg + L‐NAME groups and (d) substantially reduced the development of LV fibrosis in the hHTg + L‐NAME group. LVH in hHTg rats may be induced by sympathoadrenal system activation, circulating volume enlargement, and impairment of nitric oxide (NO) production rather than by activation of the renin‐angiotensin‐aldosterone system.

Remodeling in myocardial infarction and body surface potential maps

This study deals with the capabilities of body surface integral and departure maps to evaluate the chronic stage of myocardial infarction based on dividing the left ventricle into 12 segments. The effects of ventricular remodeling on electrocardiographic potential distributions are considered. A 61-year-old male patient was examined five times by body surface potential mapping during a period of 9 months after acute myocardial infarction. Integral maps were calculated for 60 ms after QRS onset and compared with mean data from a control group using departure maps. Integral maps showed a continual reduction of negative potentials in the lower half of the torso with time. The negative area covered the lower torso in the departure maps during the whole study, but its form and value changed. According to the location of the departure area, the surface projection of the scar moved from a position corresponding to inferior segments to a position corresponding to posterior segments. Its size also decreased. Echocardiographic examinations showed progressive enlargement of both ventricles with time. Therefore, the authors postulate that the changing pattern of body surface potential maps was mainly influenced by ventricular remodeling after myocardial infarction.

Activity of Brain Stem Groups of Catecholaminergic Cells in Tumor‐Bearing Rats

The aim of the present study was to investigate the activity of tyrosine hydroxylase (TH) immunopositive neurons, measured by Fos protein expression, in the hindbrain noradrenergic (NA) cell groups in animals exposed to visceral tumor growth for 28 days induced by intraperitoneal implantation of fibrosarcoma cells. We were also interested in determining whether brain stem NA neurons of tumor‐bearing and intact animals exhibit similarities in their response to a strong heterotypic stimulus—immobilization (IMO) stress. We found increased Fos expression in NA cells of the nucleus tractus solitarii (A2 cell group) and of the A1 cell group of tumor‐bearing rats. However, Fos expression in other brain stem NA cell groups, including A5, locus ceruleus, and A7, were similar to control rats. The effect of 60 min of IMO was evident in both groups, but there were no differences between Fos expression in brain stem NA cell groups in control and tumor‐bearing rats. This indicates that the sensitivity of NA cells in tumor‐bearing animals was not altered by the IMO‐induced stress challenge. However, whether the increased Fos expression in NA cells in tumor‐bearing animals is a consequence of a specific visceral response activated by cancer development or just a nonspecific event accompanying the cancer progression requires further study.

Segmental blood flow through intramyocardial coronary arteries during ventricular systole

The presented hypothesis assumes, in contrast with the currently prevailing view, that blood continues to flow through the coronary vascular bed even during systole. The contraction of differently oriented myocardial layers closes the penetrating branches of the coronary arteries in the interlayer boundaries. Coronary arteries of a different caliber are during systole under equal intramyocardial pressure. In accordance with the theory of elasticity, the action of an equal external pressure decreases with the lumen of the vessel and, thus, the net effect of these forces will push the blood into smaller vessels within the segment in the layer. This hydrodynamic effect empties the larger coronary arteries during systole so that they are ready for the subsequent massive influx of blood during diastole. The possible applications of this hypothesis in various physiological and pathological conditions are compatible with the present knowledge and might contribute to a more precise understanding of implicated pathophysiological mechanisms.

Gliding-window fast Fourier transform analysis of the entire QRS complex and the distribution of area ratio peaks in healthy subjects and patients with myocardial infarction

BackgroundThe high-frequency contribution (i.e. 60–120 Hz) within the QRS complex of the surface ECG is supposed to be related to the arrythmogenic substrate underlying sustained ventricular tachycardia in patients with coronary artery disease. One of the factors that prevents a wider clinical application of spectral analysis based on the fast Fourier transform is the considerable intra-individual variability of its results. This study presents a novel alternative approach of frequency-domain analysis, aimed at minimizing this methodological drawback. MethodsThe proposed method uses gliding-window fast Fourier transform analysis of the signal-averaged ECG to provide values expressing the area ratio for two predefined frequency ranges (60–120 Hz divided by 0–120 Hz). The term gliding window is derived from the methodological principle by which the window analyzed is moved from the onset of the QRS complex into the ST segment. Values of area ratios obtained for every time instant of the interval of gliding are the basis for construction of curves. These are further analyzed in order to find patterns that characterize abnormal ventricular activation, with special emphasis on the identification of arrhythmogenic correlates. ResultsIn a group of 30 healthy subjects, the distribution of area ratio peaks was characterized according to their value and timing. The distribution of area ratio peaks in 43 patients with myocardial infarction differed substantially from the normal distribution in the control group. The amplitude of the peaks and their timing was not related to the occurrence of late ventricular potentials. ConclusionThe method of gliding-window fast Fourier transform analysis eliminates the variability of results obtained by traditional spectral analysis of the ECG signal. A higher number and a different distribution of high-frequency peaks during the QRS complex in postmyocardial infarction patients reflect abnormal ventricular activation. However, late ventricular potentials are not related to a higher proportion of high frequencies in the corresponding time interval within the terminal QRS complex.

Dangerous versus useful hypertension (A holistic view of hypertension)

The authors aim to offer a holistic view on hypertension and its treatment. Their approach is fairly confrontational, particularly by suggesting that hypertension may play a role in optimizing the blood flow and enhancing oxygen delivery. An increase in blood pressure brings about a threat of catastrophes. Therefore hypertension might be considered as either a subsequent complication, or an inevitable adaptation. When changes of many complicated and complex mechanisms result in retention of sodium and water, then the treatment of this condition is so far the most logical conclusion, and possibly beneficial to the patient. This can be done by influencing the peripheral resistance or the load of vascular bed. However, in some cases a moderate overfilling of the system with no increase in heart rate could be interpreted as an optimal solution for organism that does not necessarily need to be medically treated. This may apply especially to young hypertensive patients, and in cases when no catastrophe is assumed to take place. Lowering the blood pressure to average population levels in each case, especially by means of aggressive therapy may not necessarily lead to improved tissue perfusion. A decrease in blood pressure reduces the risk of catastrophes. However, on the other hand, it can deteriorate the tissue perfusion and cause unfavorable long-term consequences.

Frequency-Domain Analysis of the QRS Complex After Treatment of Childhood Cancer with Anthracycline Cytostatics

Long-term cardiac complications, occurring several years after completion of anticancer treatment, may develop from subclinical myocardial damage induced during cardiotoxic therapy. The aim of this study was to evaluate the usefulness of frequency-domain signal-averaged ECG analysis of the QRS complex for assessing the cardiotoxicity of anthracycline cytostatics. Altogether, 172 signal-averaged electrocardiography (SAECG) registrations were performed in 50 repeatedly evaluated oncologic patients. These registrations were performed 0.2-15 years after completion of anthracycline therapy for childhood cancer. The control group consisted of 120 healthy children and young volunteers; in 20 of these controls, SAECGs were performed repeatedly. Using gliding window fast Fourier transformation within the QRS complex, values area ratio (AR) 60-120 Hz/0-120 Hz were calculated in X, Y, and Z lead. Area ratio of patients after anthracycline therapy was significantly higher than those in control group in X lead. Differences in frequency content in the QRS complex between patients and controls might signal an initial stage of anthracycline-induced myocardial damage.