Pulsatile Features of Major Arteries in Rats during Hypotension Caused by Acute Blood Loss.

The study examined the modes of pulsations of the femoral and carotid arteries of rats in situ (n=14) during acute blood loss, which sequentially caused a deep BP drop, cardiac and respiration arrest, and termination of ECG signals. When BP dropped to 19 (13; 26) mm Hg, the mechanosensitivity of passively pulsing arteries determined by the ratio of the swing range of electroimpedance oscillations of arterial segment to pulse pressure increased by 3.2 (2 ; 4) times (p<0.05). During the decrease of BP to the threshold value of 13 (8; 15) mm Hg, the arterial pulsing mode changed from passive to intermediate and then to the active one characterized by constriction of arterial segment in response to systolic elevation of BP. After cardiac arrest and BP drop almost to zero, the arterial pulsing switched to autonomic rhythmical vasomotions with the rate, which was greater than the frequency of still sustained QRS pulses of ECG. The observed phenomena are explained by transarterial hypotensive transition hypothesis, which argues that peculiarities of pulsations and vasomotions of major arteries during deep BP drop are typical of arterioles under normal or diminished BP. The study refined the hypothesis of "peripheral heart" and its role in hypo- and hypertension.

[The dependence of medical and diagnostic measures carried out in geriatrics on age, gender and the doctor's health status.]

The article discusses the probable dependence of the actions of a specialist working with geriatric patients on the age, gender, and other characteristics of this specialist. This seemingly unconventional approach to research in the field of gerontology and geriatrics reveals distinct differences in a number of aspects of clinical thinking and following clinical recommendations in doctors of different ages, genders, and in different states of their own health. On the basis of a survey of 126 doctors and an analysis of 2 394 of their opinions, the results were obtained, indicating a certain conservatism of doctors over the age of 50, especially men with extensive clinical experience. The article discusses cases of so-called self-ageism of an elderly specialist who uses in his professional actions the results of diagnosis and treatment of the age-associated pathology that he himself suffers from. It is proposed in the process of continuing education or professional training of geriatricians to take into account their age, sex and health status, as well as accompany classes mandatory determination of the biological age of the specialist.

Relationship between Passive and Active Pulsations of Rat Artery as Vascular Extension of Frank-Starling Law.

The experiments on narcotized male rats (n=30) determined the parameters of passive and active pulsatile modes of isolated segment of femoral artery in situ. Rheographic elasticity (RE) and reactivity (RR) were correspondingly determined as the ratios of peak-to-peak (p2p) magnitudes of passive and active pulsatile oscillations of arterial electroimpedance (AEI) to p2p magnitude of BP undulations. The medians and interquartile ranges of RE and RR were 6 (3; 11) and 70 (40; 110) mΩ/mm Hg, respectively. The maximal and minimal values of RE and RR in various rats differed by 50 and 80 times, respectively, and were bimodally distributed: in major group (n=23), the values were RE<15 and RR<200 mΩ/mm Hg, whereas in minor group (n=7), these parameters were RE>20 and RR>300 mΩ/mm Hg. The above ranges of RE and RR parameters were considered as the diagnostic signs of normal and pseudo-healthy rats with pathologically augmented AEI oscillations, respectively. Statistical analysis of all rats (n=30) revealed the positive correlation between RE and RR (r=0.76) with linear regression RR=31+7.6×RE. It is hypothesized that this correlation is underlain by a mechanism similar to that described by the Frank-Starling law for myocardium.

Effect of Alternating Electric Current on Pulsation Mode of Rat Major Arteries In Situ.

In experiments on narcotized rats, the electrical potential and impedance of isolated segment of the right femoral and/or carotid artery were simultaneously recorded in situ via two extracellular nonpolarizable Ag/AgCl electrodes mounted along the arteries at the interelectrode distance of 4 mm. The active, passive, and intermediate pulsing modes of arterial segment were determined according to the phase relations between its electrical impedance and BP, which was simultaneously measured in the symmetrical part of the respective left artery and used to assess pressure in the examined segment. The study assessed the effect of amplitude (0.2-2.0 mA) of alternating probe current (100 kHz), which was used to measure the electrical impedance of arterial segment, on its pulsing mode. The pulsing mode determined at the initial minimal probe current of 0.2 mA was passive with out-of-phase pulsatile oscillations of electrical impedance and BP. After elevation of the probe current amplitude to maximal level of 2 mA, these oscillations became in-phase indicating transition of the arterial segment to active pulsing mode. This transition was accompanied by appearance of arterial voltage impulses synchronized with BP upstrokes and an 11-fold median increase in the peak-to-peak value of electrical impedance oscillations with the interdecile range of 7-15 (N=28). Under moderate amplitude of probe current (0.3-0.5 mA), the intermediate mode of arterial pulsing was observed featured by a delayed, weak, and short active constriction during BP front, which was insufficient to resist and counterbalance the dilating effect of rising BP. In this case, the pulsatile oscillations of electrical impedance were smaller than those observed in active or passive pulsing modes indicating a possibility to stabilize the arterial diameter during pulsatile oscillations of BP. The effect of alternating electric current on the mode of arterial pulsation is explained with electrical model of smooth muscle cell membrane reflecting the rectifying features of potassium channels and predicting membrane hyperpolarization in response to external alternating current passing across the cell. The visibilities of therapeutic neurotropic and angiotropic stimulation with alternating electric current are discussed.

Pelvic Electric Potential as a Marker of Autonomic Dysfunctions and Risk Factor of Neurogenic Arrhythmias in Humans.

Differential high-resolution ECG (V1-V2) and pelvic electric potential measured between the coccyx and perineum were recorded simultaneously in resting supine position in men with autonomic nervous system disorders (N=37). In healthy volunteers (N=23), the effective (rms) value of PEP presented by median and interdecile range was 30 (20-80) µV within the frequency band of 0.03-80 Hz. In patients, the corresponding value was significantly higher: 140 (80-280) µV. In both groups, the amplitude harmonic spectrum of pelvic electric potential decreased monotonically with frequency according to 1/f1.6 law. In some patients (N=16), rare single or grouped high-amplitude impulses (up to 1 mV) of pelvic electric potential with total duration of about 1 sec were observed; of them, some persons (N=7) demonstrated practically one-to-one synchronous relations between these impulses and arrhythmia episodes indicating abnormal activity of the autonomic nervous system as their most probable common cause. The high-amplitude pelvic electric potential impulses were also observed in ECG records as interference signals with an amplitude attaining 50 µV. Thus, high-resolution ECG and pelvic electric potential can reveal the risk of abnormal neurogenic influences on the heart. The data obtained are discussed in relation to diagnostics of the autonomic nervous system disorders, neurogenic arrhythmias, and risk of sudden cardiac death.

[The impact of transplantation of multipotent mesenchymal stromal cells after liver resection on blood biochemical parameters in mature and old laboratory animals.]

The aim of this study was to study the effect of multipotent mesenchymal stromal cells (MMSC) transplantation on blood biochemical parameters after liver resection in Mature and old laboratory animals. The conducted studies show the ability of old laboratory animals to respond to MMSC transplantation after liver resection by reducing the severity of hepatocyte cytolysis. A comparative analysis of the biochemical parameters of Mature and old laboratory animals after liver resection should be noted a more pronounced response of mature animals in relation to the ability of the liver to synthesize urea.

[EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION].

We've estimated the cellular and metabolic part of geroprophylactic effects of short synthetic tripeptides vesugen and pinealon for correction of the biological age. 32 people (18 men, 12 women) aged 41-83 years with polymorbidity and the organic brain syndrome in remission participated in the study. The preparations of "Pinealon" and "Vesugen" have had the significant anabolic effect. They have improved the activity of the Central nervous system and other vital organs, which slows the rate of aging by biological age indicators. Vesugen has demonstrated more visible geroprophylactic effect than Pinealon. At the same time we've found the prooxidant activity through chemiluminescence. Decrease of markers CD34+ positive hematopoietic polypotent cells in blood has shown significant inhibition of hemopoiesis. Apparently, the cells have not been involved in the adaptive reactions. Pinealon and Vesugen haven't affected the degree of chromatin condensation, so they are safe on nuclear genetic level. This property should be studied in future. In geriatric practice, we recommend to apply the peptides Pinealon and Vesugen as geroprotectors anabolic neuroprotective and no antioxidant type for reducing the rate of aging in patients with the organic brain syndrome vascular and/or traumatic genesis.

Electrical Rhythms Revealed by Harmonic Analysis of a High-Resolution Cardiogram.

The front-end low-noise electronic amplifiers and high-throughput computing systems made it possible to record ECG with a high resolution in the low-frequency range including the respiration and Mayer frequencies and to analyze ECG with digital filtering technique and harmonic analysis. These tools yielded ECG spectra of narcotized rats, which contained the characteristic pulsatile triplets and pentaplets with splitting constant equal to respiration rate, as well as the peaks at respiration and Mayer frequencies. The harmonic analysis of ECG determined the frequency parameters employed to tune the software bandpass filters, which revealed the respiratory (R) and Mayer (M) waves in the time domain with the amplitudes of 20-30 µV amounting to 5% ECG amplitude. The depolarizing myorelaxant succinylcholine chloride capable to trigger various types of arrhythmias, transiently increased R-wave, inhibited M-wave, and provoked a negative U-wave within a heartbeat ECG cycle synchronously with inspiration. It is hypothesized that M-, R-, and U-waves in ECG reflect cardiotropic activity of autonomic nervous system. The respective spectral peaks in ECG can be employed to assess intensity of sympathetic and parasympathetic cardiotropic influences, their balance, and the risk of arrhythmias.

[Comparative biochemistry of process of ageing in men and women].

In the research of a number of biochemical indicators in 858 men and 899 women aged from 20 till 70 years divided into 6 compared groups depending on age and gender clear distinctions in the dynamics of the components of the lipid status, status of lipid peroxidation and antioxidant activity of the blood system, the content of middlemolecular peptides are revealed. Simultaneous determination of the biological age of the subjects also revealed a distinct gender differencies testifying to lower rate of aging of men, despite the probability of earlier, in comparison with women, development of dislipidemia and atherosclerosis. Association of the received gender distinctions both with changes of level of estrogen in women due to menopause and with the peculiarities of stressful impacts on male and female organism in different age periods is supposed.

[Comparative analysis of gerontologic prophylaxis efficiency and membranotropic action of various gas therapy].

The research was executed on 320 male patients aged 35-92 years with various polyorgan pathology in a compensation stage. The treatment by gases was used: hyperbaric oxygenation, dry carbonic acid baths, ozon therapy, hypo oxygen therapy and their combinations. On indicators of biological age various age-dependent geroprophylactics effect of gas therapy was established. On indicators of resistance of erythrocytes various safety of used modes was found.

[Dynamics of health and aging rate of patients of different age and sex in the treatment of moderate multiple pathologies].

The article presents results of investigation of the dynamics of health status of patients of different age and sex, with several non-serious diseases, in the course of their treatment in the hospital, as well as the determination of their biological age before and after the course of treatment. The clear differences in the number of diseases, their nature, duration of the treatment and its effectiveness depending on age and sex were revealed. However, at the age of older than 60 years these differences gradually disappearing. Multiple, although non-serious, pathology has a negative impact on the indicators of the biological age of men in the calendar age of 20-39 years and women in the calendar age of 20-39 and older than 60 years, but the rejuvenating effect of the treatment is extremely low. In a number of cases, in the process of treatment of multiple pathologies the indicators of initially reduced biological age get even higher and adapt to the indicators of the calendar age. The authors explain this from the position of the disturbed by the treatment adaptation of the organism to easy disease, as well as the opportunity of reviewing the biological age significantly reduced in relation to the calendar age as a pathological phenomenon similar to significantly increased biological age.

Cancer burden of breast and gynecological cancers in Bulgaria: epidemiology and clinical aspects.

PURPOSE: In Bulgaria, there are over 3700 cases diagnosed with breast cancer annually and over 3300 with gynecological cancers. The purpose of this study was to estimate the burden of breast and gynecological cancers in Bulgaria, analyzing trends of incidence, mortality and survival for the past two decades. METHODS: Data from the Bulgarian National Cancer Registry for women diagnosed with cancer of breast (C50, ICD10), cervix uteri (C53), corpus uteri (C54) and ovary (C56) during 1993 - 2009 were analyzed. Age-standardized incidence and mortality rates (ASR) per 100,000 persons were calculated using the world standard population. Average annual percent changes (AAPC) for 1993-2009 were estimated by Joinpoint regression. The observed survival was analyzed with the Life Table method for two periods: 1993-1997 and 2005-2009. RESULTS: Incidence rates of the most frequent cancers among Bulgarian women are increasing - from 1.7% to 2.6% annually. Mortality rates are decreasing significantly for breast (-0.8% annually) and increasing for corpus uteri cancers (4.9% annually). Survival for all sites increased from 3 to 8% over the study period. We observed greater proportion of cases diagnosed in stage I in 2009 than in 1993, for the 4 sites. CONCLUSION: These results indicate some differences in trends in incidence and mortality of the reviewed sites compared with other European countries, highlighting the need for more strict adherence to integrated treatment standards and the necessity of introduction of population screening programs.

[Influence of polyorgan pathology on the biological age of male and female patients of different calendar age].

The research was executed on 1433 patients, male (1055) and a female (378), of calendar age from 17 to 93 years with a various polyorgan somatic and psychoneurological pathology in remission. The polyorgan pathology worsens age-dependent indicators and increases the bioage of male and female patients. Thus sexual differences exist and practically disappear with the years. In men the polyorgan pathology makes negative influence on the age-dependent indicators in a greater degree and increases the bioage. This may be a cause of lower life expectancy for men compared with women.

Assessment of intramural blood flow and neurogenic control in intact and hypertrophic urinary bladder with harmonic analysis of bioimpedance in rats.

High-resolution impedancometry and harmonic (Fourier) analysis of variable component of bioimpedance revealed rhythmic oscillations of urinary bladder bioimpedance at the Mayer wave, respiration, and heartbeat frequencies. The power values of the corresponding Mayer, respiratory, and cardiac peaks were calculated to assess circulation in the urinary bladder wall and its autonomic nervous control at various stages of infusion cystometry in intact rats and in the rats with preliminary formed infravesical obstruction (IVO). In intact rats, filling of the bladder with physiological saline diminished the power of the first (fundamental) cardiac peak attesting to a decrease of the blood flow in the bladder wall. Simultaneously, the power of low-frequency Mayer peak reflecting sympathetic activity increased, while the power of respiratory peak decreased supposedly reflecting abatement of the parasympathetic influences. Bladder voiding was accompanied by a decrease of Mayer peak and increase of the respiratory one. Prior to infusion cystometry, the intravesical pressure in IVO rats was elevated while the power of fundamental cardiac peak was below the control value. Filling the bladder in these rats was accompanied by further decrease of the cardiac peak reflecting still greater drop in blood supply. In control rats, voiding the bladder normalized the vesical circulation assessed by the cardiac peak, while in IVO rats this peak remained decreased. The reciprocal changes of Mayer and respiratory peaks observed during infusion cystometry in the norm were replaced by unidirectional decrease in the power of both peaks in IVO rats, which probably attest to disturbance of autonomic nervous control in the hypertrophic urinary bladder in these rats.

[Pain syndrome relapse following herniated disc surgery (diagnosis and treatment)].

The aim of this study was to improve results of treatment of patients with degenerative disc disease at the long-term period after microdiscectomy by developing unique algorithm for diagnosis and treatment of persisting pain syndrome. Patients were divided into two groups. First one included 198 patients with reflex-pain syndromes. In the main subgroup (97 patients) consecutive denervation of spinal facet joints and intervertebral discs was performed to detect referred-pain syndromes. The second group included 64 patients who suffered recurrent nerve-root compression. The main cause was relapse of disc herniation. We used anterior retroperitoneal approach in 34 patients to remove herniated disc and stabilize the segment. Surgery results were assessed by visual-analogue scale and Oswestry index. Consecutive chemical denervation of spinal facet joints and intervertebral discs allowed not only to discover referred-pain syndromes, but enabled to control them. Stepwise surgical treatment resulted in clinical recovery and better outcome in 88.7% of our patients. Decompressive-stabilizing surgery with anterior interbody fusion is a pathogenetic and technically adequate treatment. The long-term follow up results of surgical treatment were better at the group of our patients operated with anterior retroperitoneal approach and anterior foraminotomy. Excellent and good results were obtained at 79.3% cases.

Fourier analysis of human finger bioimpedance variances.

Fourier analysis was employed to determine the amplitudes of spectrum components of small variations of electrical resistance (bioimpedance) in human finger recorded using an original hardware-software complex. It revealed periodic bioimpedance oscillations at the frequencies of heartbeats, respiration, and Mayer wave (0.1 Hz). These periodic variations were observed under normal conditions and during circulation arrest in the arm. It is concluded that the spectrum peaks of bioimpedance variations in the phalanx of human finger reflect periodic blood pressure changes in the major vessels and rhythmic neural control of the regional vascular tone. During normal blood flow, the greatest amplitude of rhythmic changes in bioimpedance was observed at the heart rate; it surpassed by an order of magnitude the amplitudes of respiratory oscillations and Mayer wave. In contrast, the largest amplitude of rhythmical changes of the impedance during circulation arrest corresponded to the oscillations at respiration rate, while the amplitude of variations at the heart rate was the smallest. Under circulation arrest, the maximum frequency of bioimpedance variations was approximately 1.4 Hz (the third respiratory harmonic), which indicates the upper limit of frequency range of neural modulation of vascular tone in human finger. During normal respiration and circulation, two side cardiac peaks were revealed in bioimpedance amplitude spectrum, whose amplitude reflected the depth of the respiratory amplitude modulation of pumping action of the heart. During normal breathing, the second and the third harmonics of the cardiac bioimpedance variations were split reflecting respiratory frequency modulation of the heart rate.

[Cytogenetic study of certain Tilia species]. / Tsitogeneticheskoe izuchenie nekotorykh vidov roda Tilia L.

The number of chromosomes, and mitosis and microsporogenesis were studied in Tilia europaea, T. tomentosa, T. cordata and T. platyphyllos under natural conditions of Voronezh region. Significant mixoploidy of meristematic tissue cells in seedling root tips, mitotic activity and meiosis have been demonstrated for the first time. The number of chromosomes in somatic cells varied from 28 to 140-146. The number 2n = 82 was modal for all the studied species. The number of chromosomes in T. europaea has been determined for the first time. The numbers of chromosomes in the genus Tilia are analysed on the basis of the literature and our own data. The peak of mitotic activity in seedlings and juvenile leaves (8-10%) fell on the night: 0-1 a.m. according to the winter time. Microsporogenesis is simultaneous and asynchronous. In some individual trees various abnormalities of meiosis were found: lagging in time in 1 to 5-6 chromosomes, bridges, fusions of spindles. Variations in pollen dimensions, shape and pore number were detected in many trees.

[Measurement of the concentration of free cytoplasmic calcium in the process of platelet aggregation using a fluorescent method]. / Izmerenie kontsentratsii svobodnogo tsitoplazmaticheskogo kal'tsiia v protsesse agregatsii trombotsitov fluorestsentnym metodom.

A multiwavelength method for measuring free cytosolic calcium concentration is proposed. It is based on the registration of the fluorescent spectrum of calcium--sensitive probe indo-1 and deconvolution of the spectrum into components corresponding to free and bound forms of the probe. Calcium concentration is calculated as a product of calcium-probe dissociation constant by calcium-bound to free form concentration ratio. The obtained values are independent of variations in light-scattering properties of the medium and total dye concentration in the optical channel. It is shown that during ADP-induced platelet aggregation calcium concentration rises without measurable delay after the addition of the inducer and significantly decreases by the time the aggregation begins.

Familial breast cancer. Part II: Relationships with histology, staging, steroid receptors and serum tumor markers.

PURPOSE: To identify differences in clinical characteristics, histological features, hormone receptor status, and tumor marker expression between patients with sporadic and familial breast cancer. PATIENTS AND METHODS: As in the previous Part I of this study, two groups of women with breast cancer were compared. The first group (group I) included 504 patients with a family history of breast cancer. The second (control) group (group II) consisted of 300 patients not reporting such a history in their relatives. The examined parameters in this report were stage and axillary lymph node involvement at the time of the initial diagnosis, treatment methods, hormone receptor status, and serum levels of the tumor markers CEA and CA 15.3. The data were processed and analysed using the SPSS statistical package. The statistical significance of differences between groups and subgroups was evaluated by x(2) Pearson's test and Student's paired t-test. RESULTS: Compared to sporadic cases, patients with familial breast cancer were more often diagnosed at an advanced III or IV stage; metastatic involvement of the regional lymph nodes was more frequent in group I patients. In the same group more radical surgical procedures combined with chemotherapy and local irradiation were performed. In group I the percentage of negative hormone receptors was higher (35.3% versus 22.6%; p <0.0001) for estrogen receptors (ER), and 47.6% versus 32.6% (p <0.0001) for progesterone receptors (PR). Also, in group I raised serum levels of CA 15.3 were significantly more frequent compared with group II (48% versus 35.5%, p <0.0789), and this applied also for CEA values above 50 ng/ml (10.6% versus 1.5%, p <0.0002). CONCLUSION: Familial breast cancer displays particular clinical characteristics, distinguishing it from the sporadic type of the disease. Patients with familial breast cancer are usually diagnosed at an advanced stage. Commonly, the hormone receptors are negative and the serum concentrations of tumor markers elevated. The steroid receptor status represents the most reliable predictor of response to hormonotherapy and an important prognostic factor of the patient's outcome. As a result of their particular characteristics, these patients require more radical surgical techniques combined with pre- or postoperative local radiotherapy and systemic chemotherapy.

Familial breast cancer. Part III: Genome instability and cancer risk.

PURPOSE: The purpose of part III of this study was to direct our efforts towards more detailed genetic studies, which can be used in genetic counselling of patients with breast cancer and their relatives. PATIENTS AND METHODS: We investigated 52 patients, 25 with chromosomal fragility and 17 with spontaneous chromosomal aberrations, all with familial breast cancer (study group). The control group consisted of 10 healthy women without a history of proliferative diseases or breast cancer in their families. The chromosomal fragility and spontaneous chromosomal aberrations were studied in peripheral blood lymphocytes cultured for 72 and 48 hours, respectively, at 37 degrees C, following a standard procedure. RESULTS: In the patients with breast cancer the expression of chromosomal fragility was significantly higher (19.47%) compared to 11.61% in the control group (p<0.0001). In the patients with familial breast cancer the spontaneous chromosomal aberrations were significantly higher (6.72%) compared with those of the normal individuals (1.98%, p<0.0001). In the study group spontaneous breaks in a single lymphocyte were 0.15, while they were 0.05 in the control group (p<0.0001). CONCLUSION: The values of chromosomal fragility and chromosomal aberrations have some practical and theoretical importance in genetic services. The different variants in genomic stability are related with individual breast cancer development risk. Our results support the idea that the fragile sites and chromosomal aberrations may act as predisposing factors in carcinogenesis.