M. S. Setchenska, T. Y. Christova, Z. S. Diankova, Sv. A. Alexandrov
 

 Different hormones mediate their biological responses by binding to the receptors on the cell membrane. These trigger a cascade of events that lead to generation of second messengers of the signal transduction. The transmembrane signalling initiated by some receptors is facilitated by a group of coupling proteins having GTP-binding activity, called G proteins. G-protein-coupled receptors achieve cellular responses by bringing about a change in the activity either of the adenylcyclase pathway or phosphatidylinositol bisphosphate breakdown and sphingomyelin hydrolysis with participation of protein kinase C.
Many hormonal receptors (mainly for growth factors) are participants in the so-called tyrosine-kinase signalling cascades. The insulin receptor, for example, possesses intrinsing tyrosine activity while some other receptors are activated as a result of phosphorylation by a number of cytosol tyrosine-kinases.
The cell ability to respond to a variety of hormonal signals is of the great importance for the regulation of cellular metabolism, proli-feration, differentiation as well as cell death (apoptosis). A large number of these hormonal-induced cascades are attractive pharmacological and therapeutic targets.
 

Key words: hormonal signal, transmembrane, receptor, G-proteins, adenylcyclase, protein kinase C, tyrosine kinase.
 

S. Simeonov, E. Kumchev, E. Enchev, S. Tsvetkova
 

Different noninvasive methods for the assesment of bone metabolism have been introduced in clinical practice in recent years. Together with the new densitometers, allowing exact evaluation of bone mineral content, different biochemical markers have been studied and used in clinical practice to present and estimate the process of bone remodeling. These are substances (collagen metabolites, procollagen peptides, noncollagenous matrix proteins, minerals, enzymes) released to the blood in a rate proportional to the bone resorption, resp. formation, that is their serum and urine levels correlate to the process of bone remodeling, measured by histomorphometry or calcium kinetics. The markers of bone formation are osteocalcin, alkaline phosphatase (total and bone) and type I procollagen peptide as well as some new not enough known noncollagenous matrix proteins, and the markers of bone resorption are hydroxyproline, urinary calcium excretion, pyridinoline, deoxypyridinoline, carboxy- and amino-terminal telopeptides of type I collagen, galactozylhydroxylisine, tartrate-resistant acid phosphatase. There are different methods for the assessment of the markers but recently ELISA-techniques have been mainly used, being precise and easy to perform. Most of the markers have a pronounced circadian rhythm. There is no ideal, highly specific bone marker, because of their pronounced variability (age and sex differences, dietary changes, physical activity, season, menstrual cycle, drugs intake) and in different degree – extraskeletal origin.

Currently the best bone markers are: pyridinoline crosslinks for osteoclastic activity and osteocalcin – for osteoblast activity. Bone markers have increased our knowledge and they are of great use, but the interpretation of the results aimed at clinical decision making (diagnostics or monitoring of treatment) should always be considered parallel to bone mineral density measurement.
 

Key words: bone biochemical markers, bone remodelling – resorption and formation, pyridinoline crosslinks, osteocalcin.
 

V. Tzaneva
 

Hypoglycemia is the most common complication of Type 1 Diabetes. The incidence rate, etiology and clinical characteristics of hypoglycemia were studied in 64 diabetic children followed-up by the author for 1–14 years after the onset of their disease. For a total of 319 years, 23 children (35,9%) survived 48 episodes of severe hypoglycemia which incidence rate amounted to 0,15 episodes per patient per year. In 1996, 6,25% of the observed children were affected by this complication. For one month only, 51,6% of the children suffered at least one attack of mild or slight hypoglycemia which incidence rate was 16,7 episodes per patients per year. 46% of hypoglycemic episodes have developed during the night. The children with severe hypoglycemia had a longer duration of diabetes (5,9 years versus 3,9 years), a lower HbA1c, (7,6% versus 8,5%), a higher insulin dosage (0,97 versus 0,88 UI/kg/24 h) as well as a poorer self-control. Only 8,7% of them measured every week the blood glucose level versus 34% of the children without any severe hypoglycemia. The most common reason for development of hypoglycemia was the delayed or reduced nutrition (in 41,7% of the cases) followed by insulin overdosage (in 22,9%) and increased physical activity (in 20,8%). The most frequent hypoglycemic symptoms were the following: tremor, sweating, feeling of hunger, weakness, and paleness.

A conclusion was drawn that intensified treatment did not enhance the risk of hypoglycemia on condition that the patient was well-trained and performed a regular selfcontrol.
 

Key words: Type 1 Diabetes, hypoglycemia, children, incidence, risk factors.
 

N. Ovcharova, P. Angelova-Gateva, D. Koev, G. Dakovska
 

Thirty diabetic patients of both sexes with mean age 59,6 years were investigated before and after 45 days therapy with monocomponent pork insulins. With IDDM were 3 patients and with NIDDM and secondary failure to sulphonylurea drugs were 27 patients.

The fasting and postprandial blood glucose as well as fructosamine, HbA1, superoxide dismutase (SOD) in the serum and erythrocytes, lipid peroxides, serum cholesterol and trigly-cerides were investigated before and after insulin treatment.

The 45-day treatment with monocomponent pork insulin resulted in an improvement of the metabolic control of the patients with a decrease of the serum glucose levels both fasting and postprandial, as well as a decrease of fructosamine and triglycerides.

It was found a condition characteristic for the presence of an oxidative stress before the treatment together with high serum glucose levels, fructosamine, HbA1, and lipid peroxides.

The SOD activity in the serum and in the erythrocytes and lipid peroxides were not changed after the period of the 45-day insulin treatment.

Maybe longer period of insulin treatment is needed to overcome the situation of oxidative stress in patients with long time duration of diabetes mellitus.
 

Key words: antioxidants, oxidative stress, diabetes.
 

M. Petkova
 

Glucotrol XL® is a new therapeutic formula, delivering the short-acting sulfanylurea glipizide at an effective therapeutic plasma level throughout a 24-hour period.

To eveluate the efficacy and safety of Glucotrol XL® on the glycaemic control in non-insulin dependent diabetic patients (NIDDM) an open, randomized trial was carried out.

Forty thee (21 male and 22 female)  NIDDM patients, previously treated with Minidiab with mean age 61,47±9,17 years, duration of diabetes 12,92±3,28 years, BMI 28,2±2,3 kg/m2 were included in the study.

Statistically significant lower fasting (9,12±2,19 vs. 7,8±2,77 mmol/l, p<0,05) and 2 hours after standard breakfast blood glucose level (9,77±3,83 vs. 7,9±2,7847 mmol/l, p<0,05)  was found 3 months after treatment with Glucotrol XL® compared with Minidiab treatment.

The glycaemic control, evaluated as HbA1c was improved with 0,88% after 3 months. BMI did not change (28,2±2,3 kg/m2 vs. 27,8±1,4 kg/m2) after 3 months with Glucotrol XL® treatment. 

Mean daily dose of Glucotrol XL® was statistically significant lower compared to Minidiab (6,4±2,25 vs. 16,45±7,45 mg).
The results of the present study indicate that Glucotrol XL® is safe and efficient in NIDDM patients.

The minimal dose of Glucotrol XL® given once daily produces significantly lower fasting and postprandial glycaemia and improves the glycaemic control compared to 15 mg Minidiab.
 

Key words: NIDDM, Glipizide gastrointestinal therapeutic system, efficacy.
 

Tsv. Tankova, D. Koev, L. Dakovska, R. Savova, I. Litvinenko, B. Angelova, K. Koprivarova, 
P. Angelova
 

20 patients with type 1 diabetes and severe diabetic neuropathy, of mean age 39,1±9,9 years and mean duration of diabetes 16,2±4,8 years were treated with a-lipoic acid – Tiogamma (W?rwag Pharma) for 10 days 600 mg daily i. v., thereafter 600 mg p. o. for 50 days. On the 10th day we found a decrease of 39% in pain (p<0,01) and by the end of the 2th month it fell by 81% (p<0,001). Vibration perception threshold was reduced in all patients before treatment – mean 1,83±1,6 at the great toe, 1,98±1,5 at the 1st metatarsal and 3,59±1,2 at the medial malleolus, and by the end of second month it reached mean 4,13±1,8 (p<0,001), 4,39±1,7 (p<0,02) and 5,0±0,6 (p<0,05), respectively. There was a significant improvement in the score, characterizing the severity of cardiovascular autonomic neuropathy – from 7,13±0,7 to 4,75±1,6 after the end of treatment (p<0,01). We found improvement in the Valsalva manoeure – from 1,06±0,03 to 1,15±0,06 at the 60th day; in the deep-breathing test – from 2,8±2.1 to 10,0±4,1; and in the lying-to-standing test – from 0,985±0,02 to 1,01±0,02. The change of systolic blood pressure at the lying-to-standing test fell from 20,6±10,8 to 9,4±8,8 at the 60th day. EMG showed increase in nerve conduction velocity of some nerves. Upon finishing the therapy we found changes in th laboratory parameters, characterising oxidative stress – total serum antioxidative capacity increased from 21,02 to 23,26 mg H2O2/ml/min, serum SOD activity – from 264,52 to 316,53 U/l, and erythrocyte SOD – from 0,939 to 1,125 U/gHb.
Our experience suggests that a-lipoic acid appeares to be an effective drug in the treatment of severe peripheral and autonomic diabetic neuropathy.

Key words: diabetic neuropathy, a-lipoic acid, vibration perception threshold.
 

M. Boyanov, A. Angelinin, P. Popivanov, M. Protich
 

We describe a rare syndrome in clinical practice, comprising insulin-dependent diabetes mellitus, neurogenic diabetes insipidus, optic atrophy and sensoneural deafness. A short rewiew is presented on its etiology, pathophy-siology and natural course. The clinical findings, hormonal results and special investigation data of this patient are listed. The syndrome presents with its typical characteristics as well as with other endocrine disorders. Differential diagnosis and treatment are briefly discussed.

Key words: Wolfram syndrome, diabetes mellitus, optic atrophy.
 

A.-M. Borissova
 

Osteoporosis is a chronic, progressive metabolic bone disease, which is preventable and treatable. Osteoporosis is a very important public health problem, because of its “epidemical“ occurrance in middle-age women and the osteoporosis-related fractures. It is necessary to design and implement effective programs for prevention of osteoporosis, which will improve the health status of middle-age women and will reduce the enormous costs of the treatment for osteoporotic fractures.

Risk factors for osteoporotic fractures are low bone mass, high bone turnover rate, poor bone quality.

Subjects to prevention are persons with risk factors for development of osteoporosis and persons with osteopenia.
Guidelines for antiosteoporotic prevention: 1) exercise program; 2) smoking cessation; 3) diet; 4) calcium and vitamin D supplementation; 5) hormone-replacement therapy (HRT).

Subjects to treatment are persons with osteoporosis, persons with osteopenia and other risk factors for development of osteoporosis, persons with fractures.

Guidelines for osteoporosis treatment: 1) exercise program; 2) smoking cessation; 3) diet; 4) calcium and vitamin D supplementation; 5) hormone-replacement therapy; 6) Calcitonin; 7) Bisphosphonates; 8) Fluoride; 9) Ipriflavon; 10) Raloxifene; 11) Tibulon.

The aim of the prevention and the treatment of osteoporosis is not simply a cosmetic change of bone density, but improvement in quality of life.
 

Key words: osteoporosis – diagnosis, prevention, treatment.