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Biomedical subjects

P Langer

Publications and source records attributed to P Langer.

At least 91 records · Page 5Linked to original sources

Decreased blood level of beta 2-microglobulin in the employees of a factory which produced polychlorinated biphenyls.

Under the project of evaluating the health status of the employees of CHEMKO factory (East Slovakia) which produced PCBs between 1955 and 1985, the level of beta 2-microglobulin (beta 2-m) was measured in the serum of 242 subjects from CHEMKO (Group A) and two control groups from much less polluted areas: 1,277 females from a small mountainous village (Group B), 2,179 adults from the area of a large city of Kosice (Group C). The level of thymidine kinase (TK) was measured in the groups A and B only. In addition, age-matched groups of 155 women each from all areas were evaluated. In both the whole group and the age-matched group from CHEMKO the level of beta 2-m was significantly lower (P < 0.001) than that in the respective control groups, while no difference was found in the level of TK. In conclusion, it is suggested that the decrease of beta 2-m in CHEMKO employees might be related to the immunotoxic effects of organochlorines.

Adult↗

Regulation of gene expression for lipogenic enzymes in the liver and adipose tissue of hereditary hypertriglyceridemic, insulin-resistant rats: effect of dietary sucrose and marine fish oil.

Hypertriglyceridemia is closely linked to insulin resistance. Increased dietary intake of n-3 polyunsaturated fatty acids reverses both hypertriglyceridemia and insulin resistance. To evaluate molecular mechanisms responsible for the hypotriglyceridemic effects of n-3 polyunsaturated fatty acids, the expression of genes for lipogenic enzymes in liver and white and brown adipose tissue was estimated in hereditary hypertriglyceridemic rats which underwent an euglycemic hyperinsulinemic clamp. Before the clamp, animals were fed a basal or a high (63%) sucrose diet with or without fish oil for two weeks. Results were compared to data obtained from control animals subjected to the identical protocol. In hereditary hypertriglyceridemic rats, gene expression for malic enzyme was increased in liver and in brown adipose tissue but not in white adipose tissue. The high sucrose diet raised malic enzyme mRNA levels in liver of both hereditary hypertriglyceridemic and control rats, and this effect was more pronounced in brown adipose tissue. Supplementing the high sucrose diet with fish oil led to a suppression of malic enzyme gene expression in liver and brown adipose tissue of control rats. However, this inhibitory effect was not as pronounced in the hereditary hypertriglyceridemic rats. Raised levels of fatty acid synthase mRNA in liver and brown adipose tissue of control rats fed high sucrose diet were suppressed by consumption of diet high in n-3 fatty acids. On the other hand, in hereditary hypertriglyceridemic rats fed high sucrose diet, fish oil supplementation failed to suppress increased levels of fatty acid synthase mRNA in liver and in brown adipose tissue. It appears that hereditary hypertriglyceridemic rats have elevated levels of mRNA for lipogenic enzymes in liver and brown adipose tissue and dietary control leading to an alteration of hypertriglyceridemia influences gene expression of lipogenic enzymes only under special dietary circumstances.

Adipose Tissue↗

Regulation of gene expression and activity of malic enzyme in liver of hereditary hypertriglyceridemic (hHTG) insulin resistant rat: effect of dietary sucrose and marine fish oil.

The effect of increased dietary intake of n-3 polyunsaturated fatty acids (PUFA) on hepatic malic enzyme (EC 1.1.1.40) gene expression and activity was investigated in either hereditary fixed or dietary induced hypertriglyceridemia after euglycemic hyperinsulinemic (6.4 mU/kg/min) clamp. The hereditary hypertriglyceridemic rats (hHTG) were fed for 2 weeks basal (B) or high (63 cal %) sucrose (HS) diet, with or without fish oil (FO, 30 wt % n-3 PUFA). The results were compared with the data obtained in control (C) animals subjected to identical protocol. In hHTG rats, increased gene expression [hHTG: 1.7 +/- 0.1 vs. C: 0.5 +/- 0.05 arbitrary units (AU), P<0.02] for malic enzyme (ME) was not accompanied by increased activity of this enzyme in liver [hHTG: 1.1 +/- 0.1 vs. C: 3.1 +/- 0.4 nkat/mg, P<0.001]. HS feeding raised the activity [HS-hHTG: 4.2 +/- 0.3 nkat/mg, P<0.001; HS-C: 7.5 +/- 0.9 nkat/mg, P<0.001] and mRNA levels [HS-hHTG: 10.4 +/- 0.3 AU, P<0.001; HS-C: 7.7 +/- 0.3 AU, P<0.001] in liver of both hHTG and control rats. The supplementation of HS diet with FO led to striking suppression of activity by 63 % [2.8 +/- 0.5 nkat/mg, P<0.001] and gene expression [2.9 +/- 0.2 AU, P<0.001] for ME in liver of control rats. Such inhibitory effect was not as pronounced in hHTG rats and reached about 50 % in the ME activity [HS+FO: 2.0 +/- 0.06 nkat/mg vs. HS:4.2 +/- 0.3 nkat/mg, P<0.001] or 30 % decrease in ME mRNA levels [HS+FO: 7.5 +/- 0.8 Au vs. HS:10.4 +/- 0.3 AU, P<0.001]. Thus, hHTG rats have markedly elevated levels of mRNA for malic enzyme in liver accompanied by decreased enzymatic activity. Dietary manipulations leading to alteration of hypertriglyceridemia (HS diet, omega-3 PUFA) influenced both the activity of malic enzyme and its transcription in the liver.

Journal Article↗

Inhibition of cold stimulated thyrotropin release in rats by neurotropic drugs: specific or unspecific effect?

Male Wistar Olac rats were kept in stainless steel cages at 24 +/- 1 °C. Three days before the experiment they were transferred into another room and kept 3 days at 30 °C. On the day of experiment, groups of 14-16 animals each were injected i.p. with 10 mg/kg morphine hydrochloride (MO), 1.5 mg pimozid (PI), 10 mg/kg cyproheptadine (CY) or with the combinations of MO+PI and MO+CY in the doses indicated above. Exactly after 30 min each animal was transferred to individual plexiglass cage and then a half of each group (consisting of 7-8 animals) was transferred to the cold room (4 °C), while the other half was kept at 30 °C. Precisely after 60 min the animals were quickly decapitated, the trunk blood was collected and thyrotropin (TSH) was estimated in serum using specific rat TSH radioimmunoassay kit supplied by National Pituitary Agency, Bethesda, Md. It was found that the level of TSH significantly decreased (P < 0.01) in PI injected group even at 30 °C as compared with all other groups. The same was found at 4 °C. In addition, at 4 °C the groups injected with CY, PI+MO and CY+MO showed the TSH level significantly decreased (P < 0.01) as compared with "cold control" and even with the group injected MO only. Since the animals injected with PI and CY irrespectively of MO were deeply sleeping and showed decreased body temperature and blood pressure, it was suggested that the effect of these and possibly some other drugs using for the study of the central regulation of cold stimulated TSH release may be at least partly, if not completely, unspecific.

Journal Article↗

[Organic chlorinated pollutants and the thyroid gland].

This review presents the definition of main groups of organic chlorinated pollutants (polychlorinated biphenyls, dibenzodioxines, dibenzofurans, hexachlorobenzene, hexachlorocyclohexane, DDT etc.). Moreover, the similarity of their effects with those of steroid and thyroid hormones either via steroid/thyroid receptor or via specific Ah-receptor is described. Special attention is paid to their effects on the thyroid gland in experimental conditions as well as on professionally and nonprofessionally exposed population. Finally, own preliminary data are presented which were obtained by the examination of 249 employees of the factory Chemko producing polychlorinated biphenyls in 1955-85 as compared with control groups of 218 adults from Moldava, Trebisov and Kosice and 278 women from Orava. In women from Chemko the frequency of thyroid volumes (by ultrasound) over 22,1 ml was 40/202, while that from Moldava was 16/170 (p < 0.001). In the employees of Chemko also significantly higher frequency of thyroid antibodies anti-thyroperoxidase, anti-thyroglobulin and anti-TST-receptor was found.

Animals↗

Tumor cell--endothelium adhesion in an artificial venule.

Adhesion of tumor cells to endothelial cells is a crucial step in the complex sequence of metastasis. In addition to type and local density of adhesion molecules on both cell types, shear forces exerted by the blood flow have been described to be of major importance in governing cell adhesion. Most of the experiments on the molecular basis of tumor-endothelial cell adhesion have been performed as static assays which lack shear forces. We have developed an artificial venule which shares the following in vivo characteristics. A confluent layer of endothelial cells lines the luminal surface of a glass capillary of 1 mm i.d. with pores of 30 nm diameter to allow diffusion of molecules from outside the capillary. Physiological pressure of 16 mbar, flow rate of 2 cm/s, and shear forces of 2 dynes/cm2 are maintained. This device allowed us to show that under dynamic conditions adhesion of B16 mouse melanoma cells to EA.hy926 endothelial cells is mediated most likely by a lectin-like structure on B16 cells and oligosaccharide(s) on endothelial cells. In addition, endothelial activation-independent adhesion was found to be restricted to only a fraction of endothelial cells, as the number of B16 cells that adhered was independent of the number of B16 cells applied.

Animals↗

Variational expression of functionally different macrophage markers (27E10, 25F9, RM3/1) in normal gingiva and inflammatory periodontal disease.

Keratinocytes and macrophages share under immunologically activated conditions several surface proteins. We investigated immunohistochemically with monoclonal antibodies and the APAAP technique the expression pattern of 27E10 antigen (inflammatory macrophages), 25F9 antigen (resident macrophages) and RM3/1 antigen (intermediate macrophages in healing tissue) in 29 specimen biopsies of different stages of gingivitis and periodontitis. Macrophages of each subtype exhibited a different localization pattern depending on the stage of inflammation. Furthermore, suprabasal oral gingival epithelia showed a constant 27E10 expression, independent of the stage of inflammation. In contrast, all layers of the sulcus and pocket epithelia in gingivitis and periodontitis were strongly 27E10-positive, indicating immunological activation. 25F9 antigen was expressed on basal keratinocytes independent of the stage of inflammation, whereas RM3/1 was constantly negative on keratinocytes. The expression pattern of these functionally different macrophage markers on lesional macrophages and keratinocytes indicates varying differentiation and activation and suggests a participation of these cells in the local immune response in periodontal infection.

Adult↗

Acute changes in biliary excretion of reverse triiodothyronine in rats after insulin-induced hypoglycemia: effect of glucose, verapamil, cycloheximide and actinomycin D.

Biliary excretion of reverse triiodothyronine (rT3) was estimated in rats during hypoglycemia induced by a 10-min infusion of 1 U of insulin (INS) and for the following 5 h. During that period an increase in biliary rT3 was found. This was seen also during the infusion of exogenous glucagon (10 micrograms in 1.2 ml of saline per 1 h for 5 h) given independently of INS. The infusion of glucose (1 g/kg per 50 min or 2 g/kg per 110 min) following INS infusion delayed the increase in rT3. The increase in rT3 was prevented by actinomycin D (1 mg/kg) when injected before (90 min), but not after (30 min) INS, and also by cycloheximide (2.5 mg/kg) injected immediately before INS. The same dose of cycloheximide also prevented a similar increase of rT3 during the infusion of exogenous glucagon. Verapamil (5 mg/kg divided into five doses per 4 h) blunted the increase of rT3. These data indicate that following INS injection counter-regulatory hormones may be responsible for the increased production of rT3; this altered metabolic activity apparently is dependent on protein synthesis.

Animals↗

[The present status of iodine deficiency disorders in Slovakia and perspectives in their prevention].

During 1949-1953 more than 157,000 of inhabitants were examined (i.e. more than 5% of total population) (Podoba, 1962) and the average prevalence of goitre of about 70% was found in women and about 40% in men. In the districts with the highest goitre prevalence also cretinism was found. The average values of urinary iodine in 86 villages were less than 35 micrograms/24 h. In 1951-1953 the production and mandatory consumption of iodized salt has been initiated and 10 years later a considerable decrease in goitre prevalence especially in adolescents was found. Systemic measurements during 1952-1994 showed that in about 25% of salt samples from the distribution network the iodine content was less than the requested amount of 25 +/- 10 mg KI/kg. Further decrease was found in the salt samples from households which apparently resulted in lower intake of iodine than originally expected. After 1987 some institutions joined the actions organized by ICC/IDD (International Council for Control of Iodine Deficiency Disorders), the aim of which was to evaluate the present status of iodine intake and thyroid volume namely in children and adolescents from posttotalitary countries with which it was not possible to establish any cooperation before. The examination of thyroid volume by sonographic volumetry in 4254 children and adolescents showed that 9% of values were higher than 97 percentile level of what is currently being recognized as normal range (Gutekunst and Teichert, 1993).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The present and future of providing iodinated salt to the population].

Iodine content was estimated in 401 samples of table salt (out of which 365 from the distribution network and 101 from households). The values of 85.5% of samples from the distribution network were in normal range (i.e. 25 +/- 10 mg KI/kg) while 9.8% of samples showed the values below that range. The samples from households showed lower values, only 70.2% being in normal range and 28.6% below that which was 3 times more than in those from the distribution network. Such difference may be explained by the loss of iodine from the salt during the storage due to the effects of moisture, temperature and light. However, less satisfactory iodine levels were found in the salt imported from Poland (9 of 28 samples below the normal range, i.e. 32%), Austria (5 from 9 samples below normal range, i.e. 55%) and in the sea salt (7 from 11 samples below normal range, i.e. 63%), while satisfactory values were found in the salt from Germany (all 5 samples examined were in normal range). From 1126 samples from the distribution network examined during 1981-1986 were 63.6 in normal range, while 88.4% out of 612 samples examined during the period 1987-1990 hat their iodine levels in normal range. Present data show satisfactory iodine content in the salt which justifies the assumption of satisfactory iodine intake in the population of Slovakia. (Tab. 2, Ref. 6.).

Humans↗

Thyroid volume and urinary iodine in school children and adolescents in Slovakia after 40 years of iodine prophylaxis.

The thyroid volume (by ultrasonographic volumetry) was estimated in 4,254 schoolchildren and adolescents 6-18 years of age from 12 districts of Slovakia and urinary iodine (by dry alkaline ashing followed by spectrophotometry) in 1,174 spot urine samples. No differences in thyroid volume or in iodine excretion between individual districts were found. Similarly, no differences in thyroid volume between sexes were found up to the age of 14 years, however, thereafter, such volumes were considerably higher in boys. When comparing our cummulated data with those reported by others for a population with optimal iodine intake, it was found: 1. the medians for most of the examined age groups were slightly higher, 2. the percentage of values which were higher than 97 percentiles of normal population was 3.01 for the age of 6-14 years, while that for the age of 15-18 years was 9.04. Only 35.9% of all values of urinary iodine were in the optimal range (i.e. 10-20 mud/dl), while 56.1 were less than 10 micrograms/dl and 15.9% less than 5 micrograms/dl, the remaining 8.0% over 20 micrograms/dl. In spite of long-term iodine prophylaxis (since 1949), the intake of iodine apparently is still not satisfactory, since a considerable amount of individuals appeared to be iodine deficient on the day of examination. Iodine intake, however, may be marginally sufficient up to the age of about 13-14 years, while later a higher number of enlarged thyroids was found which may be classified as goitre endemy grade I.

Adolescent↗

[Expression of the OKM5 antigen (CD36) in normal keratinocytes and inflamed mucosa].

In 62 oral mucosa biopsies of different localization and diagnoses, immunohistochemically investigated with the APAAP technique, the OKM5 expression on keratinocytes was connected with the epithelial keratinization. In parakeratotic epithelia, an obvious CD36 upregulation was detectable. Surprisingly, there was no correlation between neither the state of inflammation nor the diagnoses and the OKM5 keratinocyte expression; the oral localization by itself appeared to be responsible for the CD36 expression.

Adolescent↗

Biliary excretion of iodothyronines (T4, T3 and rT3) after administration of exogenous thyroxine: effect of glucose and insulin.

Thin polyethylene tubings were inserted into the bile duct and femoral vein to 5 groups of 6-12 rats each under pentobarbital anesthesia. The bile was collected into glass vials which were changed every 2 h for a total of 8 h. The individual groups were infused for 8 h with following solutions in a rate of 1.2 ml/h: 1. saline; 2. saline after fasting for 48 h before the experiment which was also the case in all following groups; 3.30% glucose in saline; 4. the same glucose with 1 U insulin per h; 5. 1 U insulin only in saline. After the first control interval each animal was injected 2 micrograms L-thyroxine in 0.5 ml alkaline saline into a venous cannula. In each bile sample total thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) were measured with the aid of specific radioimmunoassay and the results were expressed as ng/2 h. After the injection of exogenous T4 the excretion of this substance in bile significantly increased. In the case of T3 a significant decrease of biliary excretion was found in all fasted groups as compared with fed control (group 1). However, during the prolonged infusion of insulin resulting in severe hypoglycemia (group 5) the excretion of T3 stepwise significantly decreased, while at the same time that of rT3 significantly increased as compared with the other fasted groups including control, that infused with glucose or that infused glucose with insulin. It was suggested that this might result from the effect of counterregulatory hormones.

Animals↗

Retrospectively evaluated finding of larger thyroid volume in east Slovakian adolescents in 1987 than in 1992. Effect of Chernobyl?

Previously published data on thyroid volume in 207 boys and 220 girls aged 15-16 years obtained in January 1987 (which happened to be just by chance 8 months after nuclear accident in Chernobyl) in Kosice (located 700 km from Chernobyl) were compared with recently obtained data (January 1992) from 85 boys and 129 girls of the same age and in the same place. It was found that in 1987 the average thyroid volume in a group of both sexes was 3.4 ml higher than in 1992 (p < 0.001), while the respective difference in girls only was 4.2 ml (p < 0.001). No differences in the urinary excretion of iodine were found. Though it cannot be retrospectively proven, it is hypothesized that the increased thyroid volume in 1987 might result from some delayed changes due to irradiation thyroiditis. The data are considered to deserve further attention.

Accidents↗

Acute effect of some hormones on the metabolism of polyamines in rat liver in vivo as measured by their biliary excretion.

Groups of 6-11 adult male rats were anesthetized with pentobarbital and thin polyethylene tubings were inserted into the common bile duct and femoral vein. The bile was collected for 1 or 2 h periods within a total of 6-8 h and the excretion of putrescine (PUT), spermidine (SPD) and histamine (HA) was estimated with the aid of high performance liquid chromatography and expressed as nmol per time. In each experiment the first time interval was used as control one and then various hormones (insulin, glucagon, cholecystokinin and dexamethasone) and glucose were infused into a femoral vein. Significant increase of PUT and HA excretion was found after glucose infusion which was prevented by simultaneous infusion of insulin. Moreover, the infusion of cholecystokinin resulted in a similar significant increase of PUT, SPD and HA, while dexamethasone and glucagon were without any considerable effect. Finally, a significant increase in PUT and SPD excretion was observed after severe hypoglycemia due to the infusion of insulin. It is concluded that such approach may be used as a novel method for a study of polyamine metabolism in the liver in vivo.

Animals↗