The effect of nitric oxide inhibition and temporal expression patterns of the mRNA and protein products of nitric oxide synthase genes during in vitro development of bovine pre-implantation embryos.

This study was conducted to determine the effect of Nitric oxide (NO) inhibition in bovine in vitro development and expression analysis of the three Nitric oxide synthase (NOS) isoforms: endothelial (eNOS), neuronal (nNOS) and inducible (iNOS), mRNA and protein in bovine oocytes and embryos. Selective inhibitor of NOS, N-omega-nitro-l-arginine methyl ester (l-NAME) was applied at different doses (0, 0.1, 1 and 10 mm) in maturation (experiment 1A), culture medium (experiment 1B) and in both maturation and culture media (experiment 1C). No significant differences were observed in cleavage and blastocyst rates when oocytes were matured in the presence of l-NAME as long as the inhibitor was omitted during fertilization and culture. However, significantly lower blastocyst rates were observed when l-NAME was present at higher level (10 mm) in culture medium alone and in both maturation and culture media. In experiment 2, mRNA isolated from triplicate pools of oocytes and embryos (n = 15-20) was subjected to quantitative real time reverse transcription polymerase chain reaction to investigate the expression of eNOS, iNOS and nNOS mRNA in normal IVP bovine oocytes and embryos. While eNOS and iNOS transcripts were detected at higher level in oocytes (immature and mature), two-cell and four-cell stage embryos, the nNOS was detected only in immature oocyte, two-cell and morula stages. In experiment 3, eNOS and iNOS protein expression analysis was performed in IVP oocytes and embryos and both proteins were detected in the cytoplasm and the nuclei (weak) of oocytes and embryos. These data provide the first evidence for the role of NO production and the presence of mRNA and protein products of NOS isoforms during bovine embryogenesis.

Epidemiology of functional autonomy.

About 90% of all functional thyroid autonomies (FTA) are euthyroid for a prolonged period of time. It is estimated that more than 10% of goiter patients in iodine deficient regions and less than 10% in iodine rich areas have evidence of FTA. After the age of 40, the risk of hyperthyroidism decompensation gradually increases. This risk rises with increasing thyroid volume, nodularity and patient age. In the elderly, hyperthyroidism also occurs in the absence of goiter. After decades of iodine deficiency, especially the intake of unphysiologically high iodine concentrations may result in increased frequencies of hyperthyroidism. In iodine deficient regions, almost half of all cases of hyperthyroidism are FTA related. Following elimination of iodine deficiency, the rate of hyperthyroidism may be reduced below 10%. This will not affect the prevalence of immunogenic hyperthyroidism. The most reliable evidence of FTA is produced using the TcTU supp. test. The highly sensitive TSH0 and the TRH test are 2.5 times less sensitive. Thus, they may still indicate euthyroidism in scintigraphically compensated or decompensated FTA. The TSH0 screening is only recommended with a view to an improved cost/benefit ratio in the elderly, females above the age of 40, and ill persons. Acutely ill and psychiatric patients should be excluded. Already 1 year after the introduction of iodine into the medical treatment of thyroid disorders, Coindet reported in 1821 his epidemiologically relevant clinical observation of an increase in hyperthyroidism, predominantly of the functional autonomy type. In the meantime, detailed and universally accepted knowledge has become available on the pathogenesis and pathophysiology of functional thyroid autonomy (Gerber et al., 1985). Data on the epidemiology of functional autonomy continue to apply only to the regional population they are based on. They allow to draw conclusions on the prevalence and natural course of functional thyroid autonomy (FTA). The different forms and prevalence rates of hyperthyroidism reflect the severity and duration of the nutritional iodine deficiency on one hand and the quality of iodine prophylaxis on the other.

Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial.

BACKGROUND AND STUDY AIMS: A second-look endoscopy is often performed to evaluate the efficacy of a prior injection therapy in patients with bleeding peptic gastric or duodenal ulcers. Although this strategy is widely established, it does not rely on unequivocal data from controlled studies. In a prospective, randomized, controlled multicenter trial we assessed the effect of programmed endoscopic follow-up examinations with eventual retreatment on the outcome of bleeding ulcers in these patients. PATIENTS AND METHODS: One hundred and five patients with gastric or duodenal peptic ulcers presenting with active (Forrest type I) or recent (Forrest type IIa and IIb) bleeding upon endoscopy within four hours after admission were included in the study. Emergency treatment consisted of the sequential injection of both epinephrine (1:10,000 v/v) and up to 2 ml of fibrin/thrombin around the ulcer base. Fifty-two patients were randomized to receive programmed endoscopic monitoring with eventual retreatment in cases of Forrest type I, IIa, or IIb ulcers beginning within 16-24 hours after the index bleed. Follow-up endoscopies were continued until the macroscopic appearance revealed a Forrest type IIc or III ulcer. Fifty-three patients in the control group were closely monitored, and only received a second endoscopy when there was clinical or biochemical evidence of recurrent bleeding. The groups did not differ with respect to age, sex, site and severity of bleeding. RESULTS: The numbers of patients with recurrent bleeding were similar whether they were endoscopically monitored or not (21% versus 17%, P=0.80 chi-squared test). In addition, there was no statistically significant difference between the two groups with respect to the number of blood units transfused, need for surgical intervention, hospital stay or number of deaths (Mann-Whitney U-test). Improving local ulcer stigmata was not related to a better outcome. CONCLUSIONS: Programmed endoscopic follow-up examinations with eventual retreatment in patients locally injected for an acute or recent hemorrhage from a gastric or duodenal ulcer did not influence their outcome when compared to patients receiving only a second endoscopic intervention upon evidence for recurrent hemorrhage. Scheduled control endoscopies cannot be recommended after an initial successful endoscopic treatment of peptic ulcer bleeding when selection of the patients for second-look endoscopy is directed by the Forrest criteria.

[Effect of organized general preventive administration of iodized salt on struma incidence and ioduria in 11-16-year-old children in the Jena endemic area]. / Einfluss der organisierten allgemeinen Iodsalzprophylaxe auf die Strumafrequenz und Iodurie bei 11-16jährigen Kindern im Jenaer Endemiegebiet.

In 1988 and in 1991, i.e. two and five years after the introduction of a general iod salt supply (32 mg KJO2/kg salt) in our region, we investigated the frequency of goiters and the level of iodine excretion in urine in 504 and 336 school children of 11 to 16 years of age. In 1988 the assessment of goiter size was made by inspection and palpation according to the recommendation of WHO. 36% of the school children were found to have goiters of type I b or II. The average urine excretion of iodine amounted to 46.2 +/- 37.2 micrograms Iod/g creatinine (n = 353). In 1991 we selected school children with goiters by the same criteria and found frequency (34%) to be nearly unchanged compared to 1988. Furthermore we investigated these goiters with ultrasound and confirmed the diagnosis in 100 from 107 children. The average daily urine excretion of iodine was significantly higher in 1991 (57.7 +/- 24.8 micrograms/Iod/g creatinine, n = 328) than in 1988. However this value is below the level recommended by the WHO (minimum 75 micrograms Iod/g creatinine). Despite the increase of the iodine intake over the last years, the frequency of goiters in pubertal school children in the Jena region is endemic. This fact supports the demand for a general and sufficient iodine supply.

Treatment of juvenile goitre with levothyroxine, iodide or a combination of both: the value of ultrasound grey-scale analysis.

The effects of oral iodide, levothyroxine and of iodide and levothyroxine in combination were studied in three groups of 30 children, age 13-15 years, with euthyroid goitre. As endpoints of this study, we used thyroid volume reduction, thyroid hormones, thyrotropin and thyroid grey-scale histograms by computerized analysis. The three groups were well matched with respect to mean age, body weight and pretreatment thyroid volumes and thyroid hormones. Mean urinary iodide excretion before treatment was in the range of 30 micrograms/g creatinine, since the study was conducted in an iodine-deficient area. All three treatment regimens led to significant reductions in thyroid volume within one month. After six months on 100 micrograms of levothyroxine, thyroid volume had decreased from 14.1 +/- 4.2 ml to 8.3 +/- 2.6 ml (mean +/- SD); on 150 micrograms of iodide, from 18.5 +/- 6.2 ml to 8.8 +/- 2.7 ml; and on 100 micrograms of iodide plus 50 micrograms of levothyroxine, from 17.2 +/- 3.1 ml to 8.3 +/- 2.0 ml. When treatment was discontinued for three months, or the dosage reduced, thyroid volume increased again in the levothyroxine (to 11.3 +/- 2.5 ml) but not in the iodide group. Grey-scale values (by ultrasound, computer-aided estimation) after nine months were significantly different between the three treatment groups; no change was observed with levothyroxine, but after 150 micrograms of iodide as well as after combined treatment with levothyroxine and iodide there were marked decreases of grey-scale values; this is interpreted as reflecting a decrease in follicle size and colloid content of the thyroid which takes place after iodide supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Coronary heart disease and insulin concentration in type II diabetic patients--results of a diabetes intervention study]. / Koronare Herzkrankheit und Insulinkonzentration bei Typ II-Diabetikern--Ergebnisse der Diabetesinterventions-studie (DIS).

There is experimental, clinical and epidemiological evidence that elevated insulin levels are associated with development of atherosclerosis. Early results came from studies in non-diabetics, but the situation with respect to diabetes is more complex and not so clear. The Diabetes Intervention Study is a population-based follow-up study in newly detected type II diabetics (30- to 55-yr-old). After 5 years 431 men and 320 women received a complex check up with oral glucose tolerance tests and measurements of plasma insulin and glucose levels, fasting and 2h post-load. Regarding the metabolic parameters, the fasting and postprandial insulin levels were higher among the patients having coronary heart disease (15% of men, 36% of women), as compared to patients without this disease. In multivariate analysis sex, age, antihypertensive treatment, blood pressure, body mass index, and fasting insulin levels were independently associated with the prevalence of coronary heart disease in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with diet and/or oral antidiabetics. Body mass index and triglycerides were the only variables that independently correlated to insulin: fasting insulin = 0.4 (body mass index) + 0.1 (triglycerides) - 4,2. In future prospective studies of diabetics relating insulin concentrations to the development of vascular disease are of particular interest and necessity. Because hyperinsulinemia may contribute to accelerated atherosclerosis in NIDDM-patients, the aim of the treatment of type II-diabetes should be to correct hyperglycemia without aggravating insulin levels and other cardiovascular risk factors.

[Interdisciplinary preventive use of iodine in former East Germany following reunification and the status of packaged iodized table salt for improving alimentary iodine supply. Retrospect and prospects]. / Die interdisziplinäre Jodprophylaxe der ehemaligen DDR nach der deutschen Wiedervereinigung und der Stellenwert des jodierten Paket-Speisesalzes für die Verbesserung der alimentären Jodversorgung. Ein Rück- und Ausblick.

The general interdisciplinary iodine prophylaxis which began in the former GDR in 1985/86 led to the amelioration of the alimentary supply with iodine and to success which was taken notice of also internationally. The amelioration of the supply with iodine was above all derived from the use of iodized mineral mixtures in animal production. According to the analyses performed up to 1990 the state of development could be maintained for the time being. With the German reunification the general iodine prophylaxis was deprived of its legal fundament and with the reorganization of agriculture the expanding use of iodized mineral mixtures was no more guaranteed. Respecting the principle of voluntariness the application of iodized kitchen salt is to be propagandized above all in children, adolescents and pregnant women and the use in big kitchens, restaurants and in the foodstuff industry.

[Incidence of hyperthyroidism in the Halle area before and after introduction of general preventive iodine treatment]. / Hyperthyreoseinzidenz im Bezirk Halle vor und nach Einführung der allgemeinen Iodprophylaxe.

With an average frequency of more than 10% the former GDR is an endemic area of struma with an iodine insufficiency of second to third degree. After an effort for many years we succeeded in introducing the gradual prophylaxis with iodine preparations with the help of the action of an interdisciplinary iodine commission. After an initial addition of 25 mg of potassium iodide to the kilogram kitchen salt beginning with 1986 an iodination with 32 mg KJO3/kg was established for circa 85% of the so-called packet articles. At the same time an iodination of the mineral mixtures for the animal feed was performed. From the supplementation altogether resulted a daily iodine uptake of about 135 microgram. Apart from a reduction of strumata of newborn to lower than 1% further provable effects of the supplementation of iodine developed. Among others the losses of animals could be diminished and the production of meat and milk could be improved. In the animal production the annual losses in a value of more than 180 million GDR mark were eliminated. As the only side-effect foreseen an increase of the hyperthyroidisms by a factor between 2 and 3 appeared. It concerned both immunogenic and autonomy-caused overfunctions and is to be compared to the success of iodination known from other countries, egg. Tasmania. The cases of hyperthyroidism are transitory, in the course moderate and concern only already preformed, so-called latent form.(ABSTRACT TRUNCATED AT 250 WORDS)

A 5 year interdisciplinary control of iodine deficiency in the GDR.

The interdisciplinary iodine prophylaxis in the GDR is a successful measure for control of ID. The iodization of nearly all the salt is planed perhaps with reduction of the iodine concentration. However, next further steps may be done in cooperation of the Interdisciplinary Iodine Commission with the "Arbeitskreis: Jodmangel" in the FRG.

[Dietary iodine deficiency in East Germany following introduction of interdisciplinary preventive use of iodine]. / Zur Frage des alimentären Jodmangels in der DDR nach Einführung der interdisziplinären Jodprophylaxe.

The interdisciplinary iodine prophylaxis introduced in 1985/86 comprises the iodination of 84% of the packaged salt with 32 mg KIO3/kg salt and the use of iodized mixtures of mineral substances in animal production. At the beginning of this measure with an average renal ioduria of 19.0 +/- 1.0 micrograms J/g creatinine in the GDR there was at least still an iodine deficiency of 2nd degree. It increased from north to south: 20.3 +/- 1.0 in contrast 13.4 +/- 1.5 micrograms J/g creatinine. In the middle of 1986 a clear improvement of the supply with iodine began. The renal iodurias had more than doubled. For the GDR the mean ioduria was 43.4 +/- 0.9. The relation from north to south had, if anything, inverted: 37.3 +/- 2.1 in the north, 42-49 micrograms J/g creatinine in the centre and south of the GDR. Nearly one third of the population no more undergoes an iodine deficiency. The intrathyroidal iodine content increases. The improved supply with iodine among others is evident in: reduction of the connatal goiter below 1%, reduction of the recall rate in the TSH hypothyroidism newborn screening, normal thyroid gland mass of the newborn, reduction of the goiter frequency in children and adolescents, transient increase of the frequency of hyperthyroidism, in particular based on functional autonomies in persons older than forty years. In animal production losses of produce amounting to 181 Mic/a were eliminated.

[Changes in the thyroid status of school children in relation to improved dietary iodine intake]. / Untersuchungen zum Verhalten des thyreoidalen Status bei Schulkindern unter den Bedingungen einer verbesserten alimentären Jodversorgung.

Five years after the introduction of the iodine prophylaxis examinations on the reaction of the thyroidal state were carried out in 150 children, 9 to 15 years of age in a district of the Erzgebirge in the south of the GDR. The results of the T3-, T4- and TSH-concentrations within the serum demonstrated in all the children an euthyroid metabolic condition. The medium renal iodine elimination of 37.3 +/- 4.7 micrograms iodine/g creatinine still resulted in an ionic deficiency of 2nd degree. The thyroid volumes too measured by sonography and the thyroid masses figured out were significantly more voluminous than those of children of the same age in countries with a sufficient iodine supply since years. The incidence rate of struma in 13-15-year-old children amounted to 21 per cent. The systematic accomplishment of interdisciplinary iodine prophylactic measures will further on be essential during the next years in the GDR.

Interdisciplinary aspects of iodine prophylaxis in German Democratic Republic.

Endemic goiter still occurs in several European countries. Alimentary iodine deficiency could be proved as the main cause of endemic prevalence. Extensive epidemiologic surveys showed the great medical and economical impact of this matter for the GDR. Over 200 million Marks might be spent for diagnosis and treatment of thyroid patients per year. Also in the field of veterinary medicine and animal production iodine deficiency plays an important role. Under the conditions of iodine deficiency the fodder containing nitrate and glucosinolates (e.g. bruised rape extraction) results in additional goitrogenic effects (so-called indirect or relative iodine deficiency). Due to iodine deficiency disorders considerable losses of yields in cattle, pigs and sheep occurred. The content of iodine in animal products used for human nutrition was subsequently low. Considering the ecological implication of these problems an Interdisciplinary Iodine Commission within the Society for Endocrinology and Diseases of Metabolism of the GDR was established. Together with the governement authorities it worked out corresponding recommendations for the prophylaxis and control of its efficiency. In 1986 the iodination of most of the packed salt (32 mg KIO3/kg = = 19 mg I/kg) and the administration of iodinated mineral mixtures for the animal production were started for pigs in the whole territory of GDR and for cattle in the southern counties of the GDR only. These activities have been accompanied by information of TV as well as in the newspapers and medical journals. Thus, an improved supply of iodine to the population through iodinated table salt and animal products can be taken into account. The efficiency of these prophylactic measures is controlled interdisciplinarily.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of iodized mineral substance mixtures for cattle and swine on iodine requirements and struma prevention]. / Die Wirkung jodierter Mineralstoffmischungen für Rind und Schwein auf die Jodversorgung und Strumaprophylaxe.

In the southern districts of the GDR the calculated iodine uptake of adults was 80 micrograms/day before the iodine supplementation of the mixtures of mineral substances and the packet kitchen salt. The iodine supplementation of the mixtures of mineral substances for cattle and pig tripled the iodine content of the milk or increased it fivefold in the county of Erfurt and doubled the proportion of iodine of the meat, the inner parts and the sausage produced from them. In a daily consumption of 0.31 of milk and 250 g of meat and sausage a surplus supply of 35 micrograms of iodine for adults was calculated in the southern counties of the GDR. The 35 micrograms of iodine for the future necessary for covering the demand of iodine are certainly delivered by the iodized kitchen salt.

[Development and effectiveness of struma prevention in East Germany]. / Zur Entwicklung und Effektivität der Strumaprophylaxe in der DDR.

For the control of iodine deficiency disorders in man and animal since 1985/1986 measures have been introduced which were interdisciplinary attuned: 84% of the paketed salt are iodized (32 mg KIO3/kg) and iodized mixtures of mineral substances are used in the animal production of agricultural useful animals. The effectiveness of the iodine prevention becomes visible by an increase of the renal iodine excretion, regression of the frequency of connatal goitre and iodine deficiency disorders in the animal production. Increased manifestations of cases of hyperthyroidism as sequelae are of transient importance.

[Alimentary iodine deficiency in East Germany and its reflection in thyroid parameters following the initiation of struma prevention]. / Zum alimentären Jodmangel in der DDR und seiner Widerspiegelung in thyreoidalen Parametern nach Beginn der Strumaprophylaxe. Eine Zwischenbilanz 1985.

By regional and countrywide studies carried out in the past 10 years the occurrence of endemic goitre and iodine deficiency (ID) of grade II has been demonstrated in 1981. In 1983 till 1985 an iodized salt (25 mg KI/kg) was offered mainly in the southern counties of the G.D.R. This measure has been followed by the production of 84% of the whole paket salt iodized with stable potassium iodate (32 mg KIO3/kg) since July 1985 and delivered in all the G.D.R. Nevertheless, in the end of 1985 the persistence of iodine deficiency of grade II has yet to be stated by low renal iodine excretion, low iodine content of milk and human milk post partum. The reference values of TT3 (0.84-3.76 nmol/l) and TT4 (41.8-137.3 nmol/l) assessed in 1985 for the G.D.R. are to be interpreted before the background of an iodine deficiency of grade II.

[Status of goiter prevention in East Germany from an interdisciplinary viewpoint]. / Zum Stand der Strumaprophylaxe in der DDR aus interdisziplinärer Sicht.

The endemic goiter occurs still in many countries of Europe. Alimentary iodine deficiency could be proved as essential cause of the increased prevalence. Comprehensive epidemiological investigations refer to the medical importance of this appearance for the GDR. 200 million marks might have to be spent annually for diagnostics and therapy. Also in the production of animals sequelae of iodine deficiency play a great part. Nitrate containing and glucosinolate containing feeding stuffs (e. g. rape extraction groats) here under the conditions of the iodine deficiency additionally develop goitrogenous effects (so-called indirect or relative iodine deficiency), which lead to decrease in vitality and clinical symptoms in the agricultural useful animals cattle, pig and sheep. The iodine content of animal products was frequently low. In view of the ecological connection of these problems an interdisciplinary iodine commission was founded which in accordance with the responsible state organs elaborates adequate recommendations for the prophylaxis and control of efficiency. From 1986 was begun with the iodisation of the largest part of packet salt (32 mg KJO3/kg) und the delivery of iodized mineral mixtures for the production of animals. Thus is to be reckoned with an improved direct supply of iodine for the population by iodized table salt or an indirect one over animal product. The iodisation of the entire common salt with modified iodine concentration is striven for. Measures for the control of efficiency are introduced.

[Value of sonography in assessing nodular changes of the thyroid in an endemic goiter area]. / Zur Wertigkeit der Sonographie für die Beurteilung nodöser Schilddrüsenveränderungen im Strumaendemiegebiet.

In an area of endemic goiter 304 patients with an increased thyroid gland were examined by palpation, sonographically and partly scintigraphically. The average age was 37 (12-78) years, the average age of the patients with nodular changes of the thyroid gland 38-44 years. Patients with a diffuse struma were significantly younger with an average age of 33 years. A false-positive enlargement of the thyroid gland established by palpation occurred in 16.1% (n = 49/304). In the sonographic examination 148 out of 304 patients revealed a diffuse enlargement of the thyroid gland without provable nodular change. However, in about one third already more or less clearly characterized regressive changes could be observed. In 156 of the 304 patients 109 times solitary nodes and 47 times multinodular changes were established sonographically. In more than one third of all nodular goiters or one fifth of all patients examined a cyst was demonstrated sonographically. Two thirds of the sonographically established nodular changes were, however, solid. In 53 of all 304 examined patients could sonographically be established additional, unexpected nodes which had escaped the palpation and partly also the scintigraphic investigation. In 14% the node suspected by palpation could not be ascertained sonographically. According to the echo structure echo-poor and echo-equal solid nodes dominated. The frequency of carcinomata of the solid nodes was 6.7%. Apart from 4 echo-poorly and 2 complexly structured nodes a carcinoma of the thyroid gland demonstrated itself sonographically to the same echo. Finally conclusions are drawn for the diagnostics of the thyroid gland in the endemic area of goiter.