A. S. Alexandrov
 

Biological rhythms are inherent to all life organisms and are a necessary condition for their normal life activity. During the last years is observed a rapid development of the methods for their study.

The study, explanation, taxonomy and using in practice of this phenomenon is a part of the science of biology called chronobiology. Its aim is to answer some of the following questions: Which is the principle for measuring the time in biological systems? Do “biological clocks“ exist? Where is the “clock mechanism“ situated? How “biological clocks“ transfer their signals to the executive organs of the organism? What are the molecular mechanisms of their activity? 
Nowadays these questions are far from their final answer though the studies during the last years have highlighted some of the mechanisms of their action.

The current review describes the main characterisitcs of biological rhythms such as pe-riod, phase, acrophase, amplitude, relative amplitude, etc. The systematic terminology of biological rhythms is shown based on their periodicity, particularly the peculiarities of the circadian rhythms. More detailed attention in the review is paid to the biological rhythms of gonadotropic hormones.

The author hopes that in this review the reader may find a stimulus toward gaining an interest in the science of chronobiology necessary to reach a more dynamic understanding of the entire field of endocrinology as it relates more broadly, beyond personal health, to our environment as a whole.
 
 

Key words: chronobiology, endocrinology, circadian rhythms, oscillatio, pulsatile.
 

S. Zacharieva
 

 The menopause consitutes an important physiological change in women’s life and usually takes place around 51 years of age. Because of the increasing life expectancy, by the year 2000 the women aged 45 and more will constitute about 1/4 of the world population. This fact accounts for the growing interest in women in pre- and postmenopause and their health problems. The cardiovascular diseases are the main cause of death in women and their incidence increases dramatically after the meno-pause sets in. Arterial hypertension is less common in women than in men before the time of the menopause thereafter its prevalance in women increases. Whether the menopause ?per se“ contributes to the age-related increase in blood pressure in women is controversial. Cross-sectional studies have established higher blood pressure among post-menopausal than preme-nopausal women at a certain age, while longitudinal studies have not confirmed these findings. 
Hormone replacement therapy is the basis of current prevention of cardiovascular diseases. The mechanisms of its vasoprotective effect are complex and involve alterations in endothelial function, smooth muscle cell prolife-ration, vascular reactivity and in lipid metabolism. Further studies are needed to optimize the diagnosis and treatment of arterial hypertension in menopausal women.

Key words: arterial hypertension, menopause, hormone replacement therapy.
 

R. Savova, K. Kalinov, S. Chavrakova, K. Koprivarova, G. Popova, S. Goranova
 

The aim of this study was to dermine the incidence of type I (insulin dependent) diabetes mellitus among children aged 0-14 years in Western Bulgaria. The study included the region of Western Bulgaria with total population of 2 807 000. Two independent sources of data were used: 1. Notification of new cases in the Department of Diabetes, University Children’s Hospital in Sofia; 2. Diabetes Outpatient Centre in Sofia, local hospitals, outpatient clinics and two sanatoria, providing patients with free of charge insulin.  The completeness of ascertainment was done by capture-recapture method. In the period 1989-1994 303 newly diagnosed children with IDDM were registered with total ascertainment rate 97=34%. Mean annual age/sex specific incidence rate was 9.82/100 000/year (95% Cl 8.72; 10.94). No significant temporal variation within years was observed (c5=4.2 p>0.1). A slight, but not significant predominance of the incidence rate among females existed (10.13/100 000/year for females vs 9.54/100 000/year for males, p = 0.255). Significantly higher incidence of IDDM was found in pubertal age group (10-14 years) compared to younger age groups (0-4 and 5-9 years) (p < 0.001). Incidence rate ranged within different georgraphical districts from 6.31 to 12.03/100 000/year, being higher in Sofia town (p < 0.1). Significantly higher incidence rate was found among urban residents compared to these from rural areas (p < 0.004). We concluded that the mean annual age/sex incidence rate of IDDM among children aged 0-14 years or under in Western Bulgaria is comparable to those, reported from other Central European countries. Significant influence of pubertal age and urbanisation for increasing of incidence of IDDM was established.
 

Key words: Type I (insulin dependent) diabetes mellitus, children, incidence rate.
 

R. Kocic
 

The association between free fasting plasma insulin level and myocardial infaction, as well as the correlation of insulin level with hyperlipidemia and the level of counterregulatory hormones was studied in 24 patients surviving myocardial infarction but with no history data of diabetes mellitus and in 18 patients with history of non-insulin dependent diabetes mellitus. The results of the patients surviving myocardial infarction were compared between the first and seventh day of hospitalization. Non-diabetic patients had higher insulin at first and seventh day of surviving of myocardial infarction. Analysing the correlation between insulin and plasma lipids, positive correlation was found between insulin and cholesterol, LDL-cholesterol, triglycerides, prebeta lipoproteins and especially high correlation with apoprotein B level, but negative with the level of HDL and HDL2-cholesterol as well as with apoprotein A level. Analysing the level of free fasting insulin with the level of counterregulatory hormones, higher positive correlation was found with TSH, but negative with cortisol level in spite of its increase during myocardial infarction. The results obtained indicated that hyperinsulinemia could not be excluded as a possible risk factor for atherosclerosis and coronary disease, but most probably it may be a factor that could influence other risk factors especially plasma lipoprotein metabolism.
 

Key words: hyperinsulinemia, myocardial infarction, non-insulin dependent diabetes.
 

M. Boyanov, M. Petkova, M. Protich

Insulin resistance is known to be the result of genetic damage. The Insulin Receptor Substrate-1 (IRS-1) plays a major role in the insulin signal transduction.

Aim of this study was to produce clear evidence that the insulin resistance in a patient with lipoatrophic diabetes could be the result of structural changes in her IRS-1 gene.

We used cultured fibroblasts from that patient to obtain genomic DNA. Using specific polimerase-chain reaction (PCR) conditions we managed to amplify different fragments of her IRS-1 gene and further to clone them. Applying the classical as well as the direct sequencing methods we were able to sequence her IRS-1 gene in its full length.

We found 5 point mutation sites and a deletion site in her IRS-1 gene.

Under the assumption that those structural changes are not attributable to genetic polymorphism or to the cloning and sequencing reactions themselves, we suppose that they encode a different aminoacid sequence of the patientХs IRS-1 protein. Although none of the since known phosphorylation sites are involved, those changes are possibly the cause of the underlying insulin resistance.

The study clearly shows that molecular medicine can in the future become a major diagnostic tool.
 

Key words: Insulin-Receptor Substrate-1, IRS-1 gene, DNA analysis, mutations, insulin resistance.
 

N. Nenchev, E. Marinova, A. Djambazova, K. Todorov

Determination and attainment of ЧdryТ body weight of normohydration is a principal problem in the treatment of haemodialysis patients. This obtained by extraction of fluids (ultrafiltration) during haemodialysis, associated with extracellular and intracellular volume chan-ges. The measurement of total body bioelectrical impedance in wide frequnce range 200 Hz Р 300 kHz gives the information about these processes.

The measurements have been carried out with 34 diabetic patients on longterm dia-lysis. We established high correlation coefficient between total bioimpedance, calculated total body water (TBW) and realized ultrafiltration Р r > 0.9.

We also determined the distribution of extra- and intracellular TBW as well as the changes taking place in these compartments during haemodialisis.
 

Key words: bioelectrical impedance, impedance spectroscopy, haemodialysis, body fluid balance, diabetes mellitus.
 

P. Angelova-Gateva, M. Petkova, Y. Vladimirov, V. Krumova

The data during the last 10 years demonstrated the important role of the free radical processes in the development of atherosclerosis, coronary heart disease, diabetes mellitus, etc. As a very important factor in this direction was accepted the high total serum cholesterol, the peroxidised low density lipoproteins and the low level of the high density lipoproteins cholesterol. There is no information on the content of peroxidised lipids in the HDL.

The aim of this study was to investigate the distribution of the total thiobarbituric acid reacting substances in the fraction of the serum, containing predominantly HDL, and in the precipitate of the LDL+VLDL, answering the question Р are HDL scavengers of peroxidised lipids from the tissues to the liver.

The data received demonstrated that the HDL-chol in healthy controls was 36% from the total, but the HDL serum fraction TBARS was 60% from the total TBARS. In the group of NIDDM patients HDL-chol was 18% and the TBARS Р 43% from the total serum TBARS. The LDL-chol in the control group was 52% and the LDL+VLDL TBARS was 43%. In the group of NIDDM patients LDL-chol was 77%, and the TBARS Р 48% (in the precipitate containing LDL+VLDL).

These data demonstrated that in healthy people the observed about 36% HDL-cholesterol corresponds to more than half of the serum TBARS. In the group of NIDDM patients some difference was observed, which is interesting for future investigations. These data demonstrated the HDL as scavenger for lipid peroxides from the tissues to the liver. That is maybe its main phisiological function.

The high level of the HDL-TBARS contributes to the normal level of the total TBARS in the serum.

Key words: lipids, HDL, diabetes, free radicals
 

L. Dakovska, B. Lozanov, R. Kovacheva, R. Ivanova, Hr. Vulkova, G. Kirilov, I. Atanasova

Thyroid Associated Ophtalmopathy (TAO) is considered to be an organ-specific autoimmune disease and many investigations on the markers associated with this process are in progress.

The aim of the present study was to evaluate the prevalance of a serum autoantibodies against pig eye muscle membrane antigens, determined by Western immunoblotting, with respect to their clinical significance in patients with or without ophthalmopathy.

Fifty patients with TAO (39 w, 11 m, Class 3Р6 by ATA) and control groups of 16 patients with GraveХs disease (GD), 9 with nonautoimmune thyroid disease (NATD) as well as 15 healthy subjects all of which had no symptoms and signs of TAO, were investigated. Pig eye muscle membrane fraction was used as antigen for determining the serum autoantibodies (PEMM-Ab) after SDS-electrophoresis and Western blotting.

Tests of the sera from patients with TAO showed several bands of reactivity Р against 64 kDa, 55 kDa, 48 kDa and 95 kDa protein components with different prevalence, but these against 64 kDa antigen were the most expressed as intensity as well as frequency. Anti-64 kDa-PEMM Ab were established in 34/50 (68%) of the patients with severe active TAO as well as in 4/16 (25%) of those with GD without eye disease. None of the healthy persons as well as those with NATD revealed Ab-positivity. PEMM-Ab positivity tended to correlate with the severity and activity of the eye disease, summarized as Ophthalmic Index.

The results of this investigation confirm the usefulness of PEMM-Ab as marker of the specific autoimmunity in TAO.
 

Key words: TAO, PEMM-Autoantibodies, Ophthalmic index.