[Frequency view on genome changes testing]. / Frekvencní pohled na vysetrení odchylek genomu.

Laboratories dealing with human genome, both inherited and acquired changes, dispose with similar methods and technology. The spectrum of genetic tests is relatively broad and the number of mutations or variants tested differs substantially. Also the number of examinations carried out in individual laboratories varies. Data presented in the tables come from the year 2004 and indicate the number of examinations requested and number of positive results. Many laboratories mentioned in the registry CZDDNAL (http://www.uhkt.cz/lab_a_vysetreni/nr lab_dna_diag/dna_lab_db) perform the same tests but there is also a great number of tests carried out by only one laboratory. Reasons of the request, cost-effectiveness and clinical utility of genetic testing is being discussed.

Tissue metabolism and plasma levels of thyroid hormones in critically ill very premature infants.

Thyroid status was characterized in very preterm infants (gestational age < or =32 wk; n = 61) from birth through d 14, and in infants who died within 16 d after delivery (n = 10), where it was also correlated with metabolism of iodothyronines in peripheral tissues (brain, liver, kidney, skeletal muscle, and adipose tissue). At 3 d of life, mean plasma levels of thyroxine, triiodothyronine, and TSH started to decrease, being lower in the critically ill compared with healthy premature neonates. Activities of the three iodothyronine deiodinases enzymes (type I, II, and III, respectively) were detected in all postmortem tissue samples, except for absence of the type II activity in kidney. All activities were the highest in liver and differed in other tissues. Lack of correlation between the type I activity in liver (and kidney), and plasma levels of thyroid hormones suggested that the thyroid was the primary source of circulating triiodothyronine. On the other hand, namely in brain, correlations between activity of the deiodinases and plasma hormone levels were found which suggested a complex control by thyroid hormones of their own metabolism. High activity of type III in liver, adipose tissue, and skeletal muscle demonstrated a role of these tissues in thyroid hormones degradation. Results support the view that peripheral tissues of very preterm infants are engaged in local generation of triiodothyronine, and inactivation of thyroid hormones, but do not represent a major source of circulating triiodothyronine.

[Ret proto-oncogene mutation found in the Czech population and its predictive value for offspring of patients with medullary carcinoma of the thyroid gland]. / Mutace nalezené v Ret protoonkogenu v ceské populaci a jejich prediktivní prínos pro potomky pacientu s medulárním karcinomem stítné zlázy.

The authors completed a total of 23 pedigrees with the clinical diagnosis of medullary thyroid carcinoma (5 MEN 2A pedigrees, 11 FMTC pedigrees and 7 MTC pedigrees). Using the method of polymerase chain reaction (PCR), it was possible to define the rate of the most frequent mutations in exons 10, 11 and 16 of Ret-protooncogene present in the Czech population. The most frequent hereditary mutation found in MEN 2A and FMTC groups is substitution of thymine for cytosine in position 2095 of the transmembranous domain of the Ret-tyrosine kinase gene. Another six types of known mutations were tested.

[Thyroglobulin and microsome autoantibodies and their clinical significance in adult type I diabetics]. / Výskyt protilátek proti tyreoglobulinu a proti mikrosomum u dospelých diabetiku I. typu a jejich mozný klinický význam.

In 34 patients with type 1 diabetes manifested in postadolescent age (mean age at time of diagnosis 25 years, 18 women and 16 men) after the establishment of the diagnosis perspectively the presence of antibodies against thyroglobulin and the microsomal fraction and their relation to affection of the thyroid gland was investigated. During an investigation of 20% of the patients the authors provided repeatedly evidence of the presence of both antibodies, in 23% repeatedly only against microsomes. In 21% some antibodies were detected only once. In the course of the investigation in 65% of the patients thyroid antibodies were found. The clinically most serious affection of the thyroid gland (from the sonographic an functional aspect) was found in groups 1 an 2, while in groups 3 and 4 in the majority of patients the thyroid gland was not affected. A different pathogenesis of the disease in the above groups is suggested in the areas of DR and DQ during HLA typing, the behaviour of other antibodies and differences in dermatoglyphic examinations. Moreover there is a high ratio of women in the first two groups (61%) and conversely of men in groups 3 and 4. In the discussion attention is drawn to the different course of diabetes in patients with thyroid autoimmunity.

[The effect of fish oil on metabolic parameters in patients with type 2 diabetes mellitus associated with dyslipidemia]. / Ucinky rybích oleju na nekteré metabolické parametry nemocných s diabetes mellitus 2. typu a pruvodnou dyslipidémií.

BACKGROUND: The authors discuss the effect of administration of fish oils rich in n-3 fatty acids in diabetic patients type 2 and draw attention to the possible deterioration of glucose homeostasis. The objective of the investigation was to assess changes of the lipid and carbohydrate metabolism in type 2 diabetics with associated dyslipidaemia after enrichment of the diet with n-3 fatty acids. METHODS AND RESULTS: To 17 patients with type 2 diabetes and dyslipidaemia fish oil containing 5.5 g n-3 fatty acids per day was administered. After six weeks a decline of triglycerides was recorded (-47%, P < 0.01), free fatty acids (-27%, P < 0.01) and a rise of HDL2-cholesterol (25%, P < 0.05). The concentration of apo B, apo A-1, LDL- and HDL cholesterol did not change significantly. There were no significant changes of the blood sugar level, glycosylated haemoglobin and fructosamine. The insulin and C-peptide concentration on fasting (and after glucagon stimulation) did not change significantly. With regard to the HDL2-cholesterol and 18:0 fatty acid concentration in serum the group can be divided into responders (with a decline of glycosylated haemoglobin) and non-responders. The two groups have a reverse trend of blood sugar levels and insulinaemia and differ as to the metabolism of 18:1 n-7 acid. CONCLUSIONS: Enrichment of the diet with n-3 fatty acids in diabetics with dyslipidaemia has a favourable effect on the plasma lipid spectrum without causing deterioration of parameters of diabetes compensation. Among the group of patients some can be found where fish oil administration improves also glucose homeostasis.

Long term administration of ascorbic acid does not improve a decreased bone weight and mineral content in rats with neonatally induced streptozotocin diabetes.

Adult female rats which were neonatally made diabetic with streptozotocin showed evidence of a pronounced decrease of dry weight, ash weight, calcium, phosphorus and ascorbic acid content in the femur, as compared with control rats. However, such diabetic rats receiving large doses of ascorbic acid (100 mg/kg/day) for 85 days did not show any improvement of the above measures in spite of normalization of bone ascorbic acid content. Thus, additional ascorbic acid given to diabetic rats with osteopenia restored bone ascorbic acid content but did not improve the bone loss resulting from chronic diabetes mellitus. Additional ascorbic acid given to intact rats did not show any additional effect on the increase of bone mass and mineral content.

Hereditary hypertriglyceridemic rat: a new animal model of metabolic alterations in hypertension.

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.

[Anti-insulin antibodies and insulin resistance]. / Antiinzulinové protilátky a inzulinorezistence.

The submitted review deals with the phenomenon of immunological insulin resistance in insulin dependent diabetics which develops as a result of the presence of circulating anti-insulin antibodies as a response of the organism to administered insulin. This phenomenon is a liminal situation when anti-insulin antibodies exceed as to their concentration and affinity a certain arbitrary limit and the increasingly impaired pharmacokinetics of insulin cause a clinically manifest metabolic decompensation of the disease with the necessity of large daily doses of exogenous insulin. The authors discuss factors ensuing from the type of the administered insulin preparation, as well as the biological predisposition of the patient which potentiates the production of anti-insulin antibodies. Some laboratory methods are discussed which are used for the assessment of anti-insulin antibodies in vitro and the authors summarize individual physical variables which characterize the antibody system and which can be extracted by special mathematical procedures from experimental radioimmunoanalytical data. Only a detailed characterization of the antibody system makes it possible to evaluate the influence of this system on the pharmacokinetics of insulin.

[Cellular and molecular mechanisms of insulin resistance]. / Celulárne a molekulárne mechanizmy inzulínovej rezistencie.

In the submitted review the authors give an account of contemporary knowledge regarding the mechanism of insulin action, including a brief account of pathological conditions associated with insulin resistance. The development of knowledge of problems of insulin resistance syndromes was always very dynamic, and due to the introduction of techniques of molecular biology and genetics at the turn of the eighties and nineties, a further very marked step forward was made. Despite this it will take some time before molecular mechanisms which will confirm (or rule out?) the etiopathogenetic importance of insulin resistance not only for diabetes but also for hypertension, dyslipidaemia, IHD will be revealed.

[The effect of polyene phosphatidylcholine administration on lipid metabolism and glucose tolerance in patients with hyperlipoproteinemia IIB]. / Ovlivnení metabolismu lipidu a glukózové tolerance u pacientu s hyperlipoproteinémií typu IIB podáváním polyenového fosfatidylcholinu.

BACKGROUND: Up to now, clinical and experimental studies have brought only inconsistent data about the effectiveness of polyene phosphatidylcholine (PPC) in treatment of dyslipidemia. The aim of this randomized, double blind study was to verify the effects of the polyene phosphatidylcholine preparation Lipostabil forte R (Rhone-Poulenc-Röhrer, Köln, FRG), given orally in a daily dose 2.7 g for three months to patients with hyperlipoproteinemia type IIB and hypoalfacholesterolemia both on the plasma lipids, lipoproteins, apolipoproteins and the parameters of glucose tolerance. METHODS AND RESULTS: Administration of PPC to 30 patients with hyperlipoproteinemia type IIB and hypoalfacholesterolemia led to a significant rise of HDL-cholesterol, HDL3-cholesterol and plasma apolipoprotein A-I concentrations in comparison with the group treated with placebo. At the same time, plasma apolipoprotein B concentration slightly increased. Blood glucose, immunoreactive insulin and non-esterified fatty acid concentrations during the oral glucose tolerance test didn't change significantly after PPC administration. CONCLUSIONS: It seems PPC could be the appropriate supplement to the treatment of patients with decreased concentrations of HDL-cholesterol and plasma apolipoprotein A-I.

Changes of calcemia and magnesemia during oral glucose tolerance test (OGTT) in relation to glucose tolerance.

We have examined 56 subjects with normal glucose tolerance (NGT), 33 with impaired glucose tolerance (IGT) and 15 diabetics type II (DM) by an oral glucose tolerance test with 75 g of glucose and in addition to glycemia and C-peptide we estimated also calcemia, magnesemia, ionized calcium level (plus corrected ionized calcium level) in all time intervals. The basal glycemia and C-peptide values were different in each examined group, while the magnesium values distinguished only the DM group from the others. The corrected Ca2+ in 60 min decreased significantly in DM, while after 120 min there were no differences in the values. Magnesemia in NGT decreased after 60 and 120 min, while by IGT and DM it rised in both such intervals. The difference between IGT and DM was highly significant. Our findings give evidence about the changes in the distribution of magnesium already at an early stage of decrease glucose tolerance. The importance of this finding for an early IGT diagnostics and its further classification still remains to be definitely evaluated.

[Neuroendocrine carcinoma of the pancreas with the hyperinsulinism syndrome]. / Neuroendokrinní karcinom pankreatu se syndromem hyperinzulinismu.

In a 26-year-old woman with symptoms of hyperinsulinism explorative laparotomy revealed a pancreatic tumour metastatizing into the liver. Intensive cytostatic therapy led to a temporary inhibition of hyperinsulinism, however, in the course of two years massive infiltration of the retroperitoneum, left adrenal, gastric wall, liver, mesentery and abdominal lymph nodes by a tumour occurred. On necroptic examination the tumour had characteristics of a neuroendocrine carcinoma with carcinoid features. Part of the tumour cells were argyrophil; reliable evidence of insulin production, which during the terminal stage of the disease played again a major part in the clinical picture, was made possible only by the use of a very sensitive Czech made antibody against C peptide.

Early changes of serum N-acetyl-beta-glucosaminidase, tissue plasminogen activator and erythrocyte superoxide dismutase in relation to retinopathy in type 1 diabetes mellitus.

Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.

[Endothelial dysfunction in diabetes mellitus]. / Endoteliální dysfunkce u diabetes mellitus.

Impairment of the vascular endothelium and its functions is a common sign of several serious diseases (atherosclerosis, hypertension, vascular spasms, thromboses) and is the initial stage of vascular affection in diabetes mellitus. The endothelium plays an important role in the transformation of some substances with a cardiovascular action and it secretes itself vasoactive substances. Vascular affections in diabetes are characterized by impaired homeostasis of vasoactive substances of endothelial origin--raised levels of vasoconstrictor factors (endothelins, thromboxanes) and reduction of vasodilatating factors (prostacyclin, EDRF--endothelin derived relaxing factor) as well as disorders of their interrelations. Vasoactive agents lead at the same time also to alteration of the growth and proliferation potential of smooth muscle cells of the vascular wall and thus to remodelling of the vascular structure in diabetes. At present possible ways how to influence these processes in a favourable way are intensely studied and discussed.

[Changes in humoral pressor and depressor factors in essential hypertension during lisinopril therapy]. / Zmeny presorických a depresorických humorálních faktoru u esenciální hypertenze pri lécbe lisinoprilem.

Arterial hypertension is nowadays no longer considered an isolated disorder of blood pressure regulation but a multifactorial disease with metabolic and cellular deviations. From the therapeutic aspect of thus conceived hypertension today inhibitors of the angiotensin converting enzyme seem most promising. With regard to their assumed comprehensive effect, the authors investigated simultaneously selected pressor and depressor humoral indicators and other indicators in 21 hypertensive patients with stage I and II of essential hypertension before and after three-month treatment with an angiotensin converting enzyme inhibitor lisinopril (Prinivil, Merck, Sharp and Dohme) and compared them with findings in 21 normotensive healthy subjects. Hypertensive subjects before treatment had, as compared with normotensives, significantly lower urinary kallikrein (7.8 +/- 1.2 < 18.0 +/- 4.2 EU/24hr, a significantly higher basal plasma adrenalin (1.27 +/- 0.20 > 0.54 +/- 0.20 pmol/ml) and adrenalin after a glucose load (1.26 +/- 0.22 > 0.51 +/- 0.12) and a higher relative plasma viscosity (1.74 +/- 0.02 > 1.67 +/- 0.01). The two groups did not differ significantly as to the plasma renin activity, plasma aldosterone and fibrinogen concentration and the level of urinary prostaglandins per 24 hr: 6-keto-prostaglandin F1a, thromboxane B2 and prostaglandins E and F2a. The 75 g glucose load produced an increased plasma renin, aldosterone and noradrenaline activity in normotensives as well as hypertensives before and after lisinopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure changes induced by chronic insulin treatment in Wistar rats.

Hyperinsulinaemia may play a causal role in the development of hypertension in obese hypertensives. However, experimental evidence supporting this statement is inappropriate. The main purpose of this study was to evaluate the chronic effects of insulin administration on blood pressure, total-body glucose metabolism and urinary catecholamine excretion. After 10 weeks of insulin injection blood pressure was substantially increased in insulin-treated animals compared to those treated with saline (125 +/- 2 vs 108 +/- 2 mm Hg, p < 0.001). There were no differences in glycaemia, plasma triglyceride levels and free fatty acid levels between these two groups. Plasma level of corticosterone was increased in both insulin-treated and saline-treated rats as compared to untreated animals suggesting that the level of stress was similar in both injected groups. The urinary excretion of norepinephrine and dopamine was increased in the insulin-injected group by about 120% and 310%, respectively. Our data clearly indicate that long-term insulin administration increased blood pressure but the underlying mechanisms remain to be elucidated.

[Hyperinsulinemia--the common denominator in type II diabetes mellitus,obesity, hypertension, hypertriglyceridemia and atherosclerosis]. / Hyperinzulinémie--spolecný jmenovatel pro diabetes mellitus II. typu, obezitu, hypertenzi, hypertriglyceridémii a aterosklerózu.

During the last twenty years we witnessed a remarkable increase in knowledge of the mechanism as regards insulin action, the central hormone of metabolic regulations. Interest in cellular and molecular mechanisms of action was conditioned by a high prevalence of insulin resistance and the fact that insulin resistance holds a key position in the pathogenesis of many diseases, in particular atherosclerosis, obesity, hypertension, diabetes mellitus type II, ovarian hyperandrogenism and others. The syndrome of hyperinsulinaemia/insulin resistance is the basic component of the so-called X syndrome defined in 1988 by Reaven. It is encountered in subjects with a normal glucose tolerance but a predisposition for diabetes type II. If this disposition, probably genetic by nature, is potentiated by the central type of obesity and a sedentary lifestyle it can influence the development of hypertension and dyslipidemia. The sum of these factors promotes acceleration of atherosclerosis and frequently its premature manifestations: myocardial infarction and other cardiovascular diseases which hold the first place as regards causes of death on a world wide scale. It is important to identify but also to treat this complex not only metabolic risk factors for macrovascular diseases. It is a paradox that some drugs used as antihypertensives can cause deterioration of insulin resistance, subsequently influence in an adverse manner dyslipidemia and thus increase the metabolic risk of cardiovascular diseases. In the submitted paper the authors tried to summarize hitherto expressed views on the syndrome of hyperinsulinaemia and insulin resistance, using as a basic the results of their own work.

[Modelling the kinetics of C-peptide and hepatic extraction of insulin (in type 2 diabetics and non-diabetics with hypertriacylglycerolemia)]. / Modelování kinetiky C-peptidu a jaterní extrakce inzulinu, (u diabetiku 2. typu a nediabetiku s hypertriacylglycerolémií).

Increased glucose release from the liver which is responsible to a considerable extent for fasting hyperglycaemia in type 2 diabetics is associated with hepatic insulin resistance. Assessment of insulin extraction in the liver can therefore be useful in investigations of all pathophysiological conditions with deviations of glucose tolerance, or in the course of insulin secretion. The control group was formed by 8 healthy men, mean age 43.6 +/- 5.9 years, mean BMI 24.7 +/- 2.8. The authors examined also a group of 7 men with diabetes mellitus type II, mean age 46.7 +/- 5.9 years, BMI 31.4 +/- 8.9 and 6 men with hypertriacylglycerolaemia, mean age 44.2 +/- 3.1 years and mean BMI 26.2 +/- 1.4. All were examined by the intravenous glucose tolerance test with frequent blood sampling. In every sample the blood sugar level, insulin level and C-peptide level were assessed. The data were evaluated and the "hepatic insulin extraction index" was thus obtained. The "hepatic insulin extraction index" was significantly lower in type 2 diabetics throughout the experimental period (0-180 min.) as well as during individual intervals evaluated (0-20 min. and 20-180 min.). In subjects with hypertriacylglycerolaemia this index was lower only during the 0-20 min. interval. Changes of the "hepatic insulin extraction index" in patients with hypertriacylglycerolaemia do not reach the intensity recorded in diabetics and may thus indicate a milder grade of hepatic insulin resistance.

[Albuminuria and N-acetyl-beta-glucosaminidase activity in a prospective study of type I diabetics]. / Albuminurie a aktivita N-acetyl-beta-glukosaminidázy v prospektivní studii u diabetiku I. typu.

The authors investigated a group of 47 type I diabetics in a prospective study extending over 8 years. Every year they evaluated the albuminuria and the N-acetyl-beta-glucosaminidase (NAG) activity in serum and urine and the results were compared with the state of compensation of diabetes and with the clinical finding on the ocular fundus. During the eight-year period newly manifested microalbuminuria developed in 8 of 32 patients (25%) who at the onset had a normal finding. In patients with newly manifested microalbuminuria the authors found a significant rise of the fructosamine serum concentration (p < 0.05) and at the same time a rise of serum NAG activity (p < 0.05). A positive correlation was proved between the serum NAG activity and glycated haemoglobin (r = 0.67, p < 0.01). In 13 patients (28%) in the course of the eight-year period the finding on the ocular fundus deteriorated. In these patients the NAG serum activity was elevated already at the onset of the investigation, while albuminuria rose in the course of the mentioned period. Dynamic changes of the NAG serum activity along with albuminuria can serve as bio-chemical markers of developing microangiopathy the manifestation of which is hastened by deteriorated compensation of diabetes.