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Abstract Transcription, a critical process in molecular biology, has found many applications in RNA synthesis, including mRNA vaccines and RNA therapeutics. However, current RNA characterization technologies suffer from amplification and enzymatic biases that lead to loss of native information. Here, we introduce a strategy to quantitatively study both transcription and RNA polymerase behaviour by sizing RNA with RNA nanotechnology and nanopores. To begin, we utilize T7 RNA polymerase to transcribe linear DNA lacking termination sequences. Surprisingly, we discover alternative transcription termination in the origin of replication sequence. Next, we employ circular DNA without transcription terminators to perform rolling circle transcription. This allows us to gain valuable insights into the processivity and transcription behaviour of RNA polymerase at the single-molecule level. Our work demonstrates how RNA nanotechnology and nanopores may be used in tandem for the direct and quantitative analysis of RNA transcripts. This methodology provides a promising pathway for accurate RNA structural mapping by enabling the study of full-length RNA transcripts at the single-molecule level.

Plasma volume (PV) undergoes constant and dynamic changes, leading to a large intra-day variability in healthy individuals. Hydration is known to induce PV changes; however, the response to the intake of osmotically different fluids is still not fully understood. In a randomized controlled crossover trial, 18 healthy individuals (10 females) orally received an individual amount of an isotonic sodium-chloride (ISO), Ringer (RIN), or glucose (GLU) solution. Hemoglobin mass (Hbmass) was determined with the optimized carbon monoxide re-breathing method. Fluid-induced changes in PV were subsequently calculated based on capillary hemoglobin concentration ([Hb]) and hematocrit (Hct) before and then every 10 minutes until 120 min (t0–120) after the fluid intake and compared to a control trial arm (CON), where no fluid was administered. Within GLU and CON trial arms, no statistically significant differences from baseline until t120 were found (p > 0.05). In the ISO trial arm, PV was significantly increased at t70 (+138 mL, p = 0.01), t80 (+191 mL, p < 0.01), and t110 (+182 mL, p = 0.01) when compared to t0. Moreover, PV in the ISO trial arm was significantly higher at t70 (p = 0.02), t110 (p = 0.04), and t120 (p = 0.01) when compared to the same time points in the CON trial arm. Within the RIN trial arm, PV was significantly higher between t70 and t90 (+183 mL, p = 0.01) and between t110 (+194 mL, p = 0.03) and t120 (+186 mL, p < 0.01) when compared to t0. These results demonstrated that fluids with a higher content of osmotically active particles lead to acute hemodilution, which is associated with a decrease in [Hb] and Hct. These findings underpin the importance of the hydration state on PV and especially on PV constituent levels in healthy individuals.

The title compound, [IrZnI2(C10H15)(C3H9P)2]·0.5C6H6 or [Cp*(PMe3)2Ir]-[ZnI2] (Cp* = cyclo-C5Me5) was obtained and characterized as its benzene solvate [Cp*(PMe3)2Ir]-[ZnI2]·0.5C6H6. The bimetallic complex in this structure contains the Lewis-acidic fragment ZnI2 bonded to the Lewis-basic fragment Cp*(PMe3)2Ir, with an Ir—Zn bond distance of 2.452 (1) Å. The compound was obtained by reacting [Cp*(PMe3)IrI2] with 2-Ad2Zn (2-Ad = 2-adamantyl), resulting in the reduction of the IrIII complex and formation of the IrI–ZnII adduct. The crystal studied was a twin by non-merohedry with a refined BASF parameter of 0.223 (1).

The synthesis and structural characterization of the molecular compound (μ3-benzene-1,2-dithiolato)hexacarbonylbis(μ3-1,1,1,4,4,4-hexafluorobut-2-ene-2,3-dithiolato)tricobaltmolybdenum, [Co3Mo(C4F6S2)2(C6H4S2)(CO)6] or Mo(tfd)2(bdt)(Co(CO)2)3 (tfd is 1,1,1,4,4,4-hexafluorobut-2-ene-2,3-dithiolate and bdt is benzene-1,2-dithiolate), are reported. The structure of the molecule contains the molybdenum tris(dithiolene) complex Mo(tfd)2(bdt) coordinated as a multidentate ligand to three cobalt dicarbonyl units. Each of the three cobalt centers is relatively close to molybdenum, with Co...Mo distances of 2.7224 (7), 2.8058 (7), and 2.6320 (6) Å. Additionally, each of the cobalt centers is bound via main-group donor atoms, but each one in a different way: the first cobalt atom is coordinated by two sulfur atoms from different dithiolenes (bdt and tfd). The second cobalt atom is coordinated by one sulfur from one tfd and two olefinic carbons from another tfd. The third cobalt is coordinated by one sulfur from bdt and two sulfurs from tfd. This is, to the best of our knowledge, the first structurally characterized example of a molybdenum (tris)dithiolene complex that coordinates to cobalt. The F atoms of two of the –CF3 groups were refined as disordered over two sets of sites with ratios of refined occupancies of 0.703 (7):0.297 (7) and 0.72 (2):0.28 (2).

The complex cation in the title compound, (carbonyl-1κC)(1η5-pentamethylcyclopentadienyl)(μ-2,3,9,10-tetramethyl-1,4,8,11-tetrathiaundeca-2,9-diene-1,11-diido-1κ2S,S′′′:2κ4S,S′,S′′,S′′′)ironnickel(Fe—Ni) hexafluorophosphate, [FeNi(C10H15)(C11H18S4)(CO)]PF6 or [Ni(L′)FeCp*(CO)]PF6, is composed of the nickel complex fragment [Ni(L′)] coordinated as a metalloligand (using S1 and S4) to the [FeCp*(CO)]+ fragment, where (L′)2− is [S—C(Me)=C(Me)—S—(CH2)3—S—C(Me)=C(Me)—S]2− and where Cp*− is cyclo-C5(Me)5− (pentamethylcyclopentadienyl). The ratio of hexafluorophosphate anion per complex cation is 1:1. The structure at 150 K has orthorhombic (Pbcn) symmetry. The atoms of the complex cation are located on general positions (multiplicity = 8), whereas there are two independent hexafluorophosphate anions, each located on a twofold axis (Wyckoff position 4c; multiplicity = 4). The structure of the new dimetallic cation [Ni(L′)FeCp*(CO)]+ can be described as containing a three-legged piano-stool environment for iron [Cp*Fe(CO)`S2'] and an approximately square-planar `S4' environment for Ni. The NiS2Fe diamond-shaped substructure is notably folded at the S—S hinge: the angle between the NiS2 plane and the FeS2 plane normals is 64.85 (6)°. Largely because of this fold, the nickel–iron distance is relatively short, at 2.9195 (8) Å. The structural data for the complex cation, which contains a new unsaturated `S4' ligand (two C=C double bonds), provide an interesting comparison with the known NiFe hydrogenase models containing a saturated `S4'-ligand analogue having the same number of carbon atoms in the ligand backbone, namely with the structures of [Ni(L)FeCp(CO)]+ (as the PF6− salt, CH2Cl2 solvate) and [Ni(L)FeCp*(CO)]+ (as the PF6− salt), where (L)2− is [S—CH2—CH2—S—(CH2)3—S—CH2—CH2—S]2− and Cp− is cyclopentadienyl. The saturated analogues [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ have similar Ni—Fe distances: 3.1727 (6), 3.1529 (7) Å (two independent molecules in the unit cell) and 3.111 (5) Å, respectively, for the two complexes, whereas [Ni(L′)FeCp*(CO)]+ described here stands out with a much shorter Ni—Fe distance [2.9196 (8) Å]. Also, [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ show interplanar fold angles that are similar between the two: 39.56 (5), 41.99 (5) (independent molecules in the unit cell) and 47.22 (9) °, respectively, whereas [Ni(L′)FeCp*(CO)]+ possesses a much more pronounced fold [64.85 (6)°]. Given that larger fold angles and shorter Ni—Fe distances are considered to be structurally closer to the enzyme, unsaturation in an `S4'-ligand of the type (S—C2—S—C3—S—C2—S)2− seems to increase structural resemblance to the enzyme for structural models of the type [Ni(`S4')FeCpR(CO)]+ (CpR = Cp or Cp*).

The title compound, hexakis[μ3-1,2-bis(trifluoromethyl)ethene-1,2-dithiolato]-octahedro-hexapalladium(II), [Pd(C4F6S2)]6, crystallizes as its benzene solvate, [Pd(tfd)]6·2.5C6H6, where tfd is the dithiolene S2C2(CF3)2. The molecular structure of [Pd(tfd)]6 is of the hexametallic cube type seen previously in three examples of hexameric homoleptic palladium monodithiolene structures. All structures have in common: (a) the cluster closely approximates a cube containing six PdII atoms, one at the centre of each cube face; (b) 12 S atoms occupy the mid-points of all 12 cube edges, providing for each PdII atom an approximately square-planar S4 environment; (c) each S atom is part of a dithiolene molecule, where the size of the dithiolene ligand necessitates that only sulfur atoms on adjacent cube edges can be part of the same dithiolene. This general cube-type framework has so far given rise to two isomeric types: an S6-symmetric isomer and a C2-chiral type (two isomers that are enantiomers of each other). The structure of [Pd(tfd)]6 is of the C2-type. Out of the 12 CF3 groups, three are rotationally disordered over two positions. Further, we answer the question of whether additional, previously undiscovered, isomers could follow from the cube rules (a) through (c) above. An exhaustive analysis shows that no additional isomers are possible and that the list of isomers (one S6 isomer, two C2 enantiomers) is complete. Each isomer type could give rise to an unlimited number of compounds if the specific dithiolene used is varied.

Ulrich Feifel1, Gudrun Wallenstein1, Karl-Ludwig Rominger1, Dirk Trommeshauser2, Juliane Platz21Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216 Ingelheim, Germany; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorf Straße 65, 88397 Biberach, GermanyAbstract: Data are presented from two randomized, double-blind, placebo-controlled studies in which the tolerability of tiotropium Respimat® Soft Mist™ Inhaler (SMI), a new-generation, propellant-free device for use in COPD, and the ocular safety of tiotropium were examined. In Study 1, 36 healthy males received tiotropium 8, 16, or 32 µg (n = 9/dose) or placebo (n = 3/dose level), administered once daily via Respimat® SMI for 14 days. Safety and pharmacokinetics were evaluated. In Study 2, 48 healthy males received tiotropium 0.02, 0.04, 0.08, 0.16, 0.28, or 0.40 µg (n = 6/dose) or placebo (n = 2/dose level), applied as two drops to one eye (the highest dose was a significant multiple of a percentage of the proposed Respimat® SMI clinical dose that could be inadvertently deposited in the eye). Ocular parameters were measured over 24 hours. Tiotropium Respimat® SMI at doses up to 32 µg was well tolerated in Study 1; typical dose-dependent anticholinergic adverse events of mild-to-moderate intensity were observed. In Study 2, ocular tiotropium administration did not affect pupil diameter, pupillary reflex, intraocular pressure, or accommodation. Tiotropium Respimat® SMI was well tolerated. Inadvertent ocular exposure to tiotropium up to 0.40 µg is unlikely to result in ocular adverse effects.Keywords: Respimat® Soft Mist™ Inhaler, tiotropium, anticholinergic, chronic obstructive pulmonary disease

Nonlinear optical microscopy was used to image the localization of astaxanthin accumulation in the green alga, Haematococcus pluvialis. Polarization-in, polarization-out (PIPO) second harmonic generation (SHG) and third harmonic generation (THG) microscopy was applied to study the crystalline organization of astaxanthin molecules in light-stressed H. pluvialis in vivo. Since astaxanthin readily forms H- and J-aggregates in aqueous solutions, PIPO THG studies of astaxanthin aggregates contained in red aplanospores were compared to PIPO THG of in vitro self-assembled H- and J-aggregates of astaxanthin. The PIPO THG data clearly showed an isotropic organization of astaxanthin in red aplanospores of H. pluvialis. This is in contrast to the highly anisotropic organization of astaxanthin in synthetic H- and J-aggregates, which showed to be uniaxial. Since carotenoids in vitro preferentially form H- and J-aggregates, but in vivo form a randomly organized structure, this implies that astaxanthin undergoes a different way of packing in biological organisms, which is either due to the unique physical environment of the alga or is controlled enzymatically.

In the wake of the redefinition of the kilogram, the last unit of the International System of Units (SI) that is still based on a man-made artefact, discussions were launched on the necessity of redefining other units, amongst other the unit mole. Since 1971 the mole is defined as the amount of substance of a system that contains as many elementary entities as there are atoms in 0.012 kilogram of carbon 12. The symbol of the unit is 'mol'. When the mole is used, the elementary entities must be specified and may be atoms, molecules, ions, electrons, other particles, or specified groups of such particles. The definition is based on the pre-existing choice to set the relative atomic mass of carbon 12 equal to 12 exactly. In the proposed new definition the mole is the amount of substance containing exactly 6.022 141 79 × 1023 atoms or molecules, ions, electrons, other particles, or specified groups of such particles, i.e. the Avogardo constant would have a fixed value without an uncertainty. This contribution critically examines the submitted arguments to justify the proposed redefinition of the unit mole by 2011 for their persuasive power to change a scientific and cultural good such as a unit of measurement. As shown, there are no convincing scientific arguments for a redefinition of the mole that stand a closer examination. The current definition is well understood, established in science and technology for almost 50 years and is still up to date.

In the title compound, (C24H20As)[Pt(C4F6S2)2], the cation lies on a twofold rotation axis while the anion has crystallographic inversion symmetry. The PtII ion is in a slightly distorted square-planar coordination environment. The F atoms of both unique –CF3 groups are disordered over two sets of sites, the ratios of refined occupancies being 0.677 (15):0.323 (15) and 0.640 (16):0.360 (16). The crystal structure is the first to date of a monoanionic [Pt(tfd)2]− species [tfd is 1,2-bis(trifluoromethyl)ethene-1,2-dithiolate] with a non-redox-active cation.

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)

It is reported on the clinical experiences in the care of 19 patients with insulinoma. The relatively simple proof of the existence of an insulinoma which is possible by the determination of insulin is performed by the recognition of a pathognomonic insulin--blood glucose--quotient in fasting state and in the fasting test, respectively. Stimulation tests are less evident and do not lead to any further clinically relevant information. The difficulty of the diagnosis consists in the localisation of the tumour. Without clinically urgent necessity an operation without localisation of the tumour should not be performed.

It is reported on a now 48-year-old male with a multiple endocrine neoplasia (MEN I). The most impressive symptomatology issued from a relapsing organic hyperinsulinism the cause of which were multiple islet cell tumours. Up to now the hyperparathyroidism was not mastered by the removal of two adenomas of the parathyroid gland. As third fact in this clinical picture, called also Hiob syndrome, the hypophyseal manifestation developed in form of a space occupation with a hypersomatotropism, the course and final clarification of which are still open.

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 values of the per cent 24 h radioiodine uptake in the GDR are above 60--70% and speak for a low alimentary intake of iodine or renal excretion of iodine below 40 micrograms J/d. Like the struma prevalences they show a tendency increasing from north to south and characterize the whole European situation of iodine deficiency including its decrease from west to east. The mean values of radioiodine uptake of 71.7 +/- 13.2% (n = 110) in euthyroids of the district of Karl-Marx-Stadt correspond to the iodine deficiency as it occurs approximately in the districts of Erfurt, Dresden, Munich or Freiburg/B. The alimentary iodine intake of 38.4 +/- 17.2 micrograms J/d and the renal iodine excretion of 29.9 +/- 16.1 micrograms J/d, calculated from the 24 h radioiodine accumulation values of 40 euthyroid persons by means of a mathematical model developed by Oddie and co-workers were low. The latter only slightly differed (P less than 0.05) from its chemically estimated excretion of iodine in the urine: 23.1 +/- 16.9 micrograms J/g creatinine (n = 73). Between the calculated and chemically estimated excretion of iodine there was a relatively strict correlation of r = 0.68 (n = 26; P less than 0.001). The introduction of an iodine prophylaxis is regarded as an urgent necessity. Later on a new estimation of the regional "normal values" is necessary for the per cent radioiodine uptake.

10% of the inhabitants of the district of Naumburg were examined for their state of the thyroid gland. The average morbidity of struma was 25.2%. Above all the struma stages I and II were found. The maxima of frequency were in the age groups of the 20--29-year-old persons with 68% in the females and 27.4% in the males. Of the 585 inhabitants of the village Grossjena (85% of the total population) 32.9% has a struma. The patterns of distribution corresponded, apart from a second peak in the females at the time of the climacterium, to the patterns found in the whole region of Naumburg. The average iodine excretion in the urine of 19.9 micrograms/g creatinine was still undercut by the 12- to 15-year-old pupils of this village with 14.8 micrograms/g creatinine. The relation of female to male carriers of struma was on an average at 2.5 : 1. In individual age groups the sex-conditioned differences were eliminated. Relation of sex, excretion of iodine and frequency of struma confirm the endemic character of the struma disease in the district of Naumburg and confirm an iodine deficiency of IInd to IIIrd degree. The results intensely emphasize the necessity of a centrally regulated iodate prophylaxis.

In 119 children and adolescents with restricted growth whose secretion of growth hormone (hGH) was investigated in the insulin hypoglycaemia test, different hGH-secretion patterns were found. 52.1% of the investigated persons showed a prestimulatory stress-conditioned hGH-secretion. There were no relations to age or to sex. The hypoglycaemia-conditioned secretion of hormone following this spontaneous release has quantitatively no relation to the size of the decrease of blood sugar. However, it is also determined by the trend of secretion in the pretest-phase. Different modes of synthesis and release are the cause for this behaviour. High spontaneous hGH-levels decrease the hypoglycaemia effect of the intravenously applied insulin. In 33.9% of the cases the levels of the growth hormone are lower during the proper test phase or only as high as in the preparation time. Twelve times the poststimulatory values simulated a hyposomatotropism. The eventual importance of the secretion patterns remains up to now unclear for the longitudinal growth.

Knowledge about the physiology of the fetal and maternal regulating circle of the thyroid gland is the prerequisite for the right valuation of thyroidal parameters and for a risk-poor treatment of diseases of the thyroid gland during pregnancy. The conditions of the passage at the fetoplacental unit require particular attention in the use of thyroid depressants. Hyperthyreoses as well as bland strumae may be increased in their distinction by a pregnancy. Maternal hyperthyroidism has often a mild course. While thyreostatic drugs must be applied in their least effective dosage, for the substitution with thyroid hormones there is a higher demand than in non-pregnant women. Fetus and newborn as well as the mother need a narrow-mashed control which should be performed interdisciplinarily in a special consulting.

An islet cell tumor, characterized by proinsulin level significantly elevated above normal human pancreas, has been found to contain insulin- and glucagon-degrading activity. Examination by chromatography on Sephadex G-75 of the degradation products formed from insulin showed A chain, and B chain rich-A chain aggregate as previously found with rat pancreatic islets. There was, however, little conversion of A chain to low molecular weight components indicating that insulinoma peptidase that has been found to degrade glucagon at about pH 6.8 degraded that A chain to a markedly lower rate. In contrast to the insulin-degrading activity, which was activated by glutathione in the presence of EDTA, the peptidase activity was not affected by the thiol compound. The activity of the peptidase was markedly inhibited by chelating agents, i.e., EDTA and o-phenanthroline, whereas chymotrypsin and trypsin inhibitors, i.e., TOS-PheCH2Cl, TOS-LysCH2Cl, soybean and pancreas trypsin inhibitor were found to have no effect.

In experiments with laboratory mice of different age (3, 9, 13, 18, 31 and 52 weeks old) directed changes of the daily pattern of plasma insulin concentration depending on the development stage of the animals could be quantified. The circadian acrophase undergoes a negative shift from the end of dark/beginning of light period in 3-weeks-old mice to the end of light/beginning of dark period in adults. The amplitude decreases up to an age of 9 weeks, whereas the amount of ultradian components is high, and increases during further development. Similar changes could be obtained for the daily pattern of feeding activity, occurring however some weeks earlier. The result is a temporary desynchronisation. In adult animals the phase correlations are relatively stable. The plasma insulin concentration reaches its maximal value before the maximum of feeding activity, thus stimulating a high food consumption and utilisation rate.

About 30% of amenorrhoeic women have a disturbed prolactin secretion. In about 10% the cause is a hypophyseal-suprahypophyseal tumour. Taking into consideration the degree of severity of the galactorrhoe, the amenorrhoe is connected with incontinence of milk. Also disturbances of the male potency may with partly similar symptomatology be conditioned by a hyperprolactaemia. For the development of hypogonadism the physiologic effect of prolactin gives sufficient explanations. With the introduction of dopaminergic substances which influence the disturbed regulating circle hypothalamus-hypophysis in the sense of an inhibition of the prolactin secretion new conservative possibilities for the therapy of disturbances of fertility are the result. With adequate recommendations for the radioimmunologic determination of prolactin the WHO made allowance for the central position of prolactin in the pathogenesis of hypogonadism. In particular the existence of hypophyseal microadenomas presumes a close cooperation between gynaecologists, radiologists, ophthalmologists and endocrinologists in the clarification of hyperprolactinaemic disturbances of fertility.

In 11 patients with acromegaly the peripheral thyroid hormones were determined and a TRH-TSH-test was carried out. Depending on the result of the determination of the growth hormone the patients were classified into two groups (active and inactive acromegaly). The serum thyroxin level and the T3-binding capacity were normal. Only in a few patients decreased triiodotyronine levels were found. Independent of the degree of activity of the acromegaly positive as well as negative TRH-TSH-tests were found. The struma in patients with acromegaly which is frequently to be observed seems to be in a causal connection with this disease. The examination show altogether that the control of the function of the thyroid gland and the TRH-TSH-test do not deliver an essential contribution for the diagnostics of acromegaly itself.

The combination of sonography and biopsy in the diagnostics of the thyroid gland results in a reliability of 100%. Thus the routine application effective diagnostics and therapy is justified. The course control after emptying of the cyst is simplified, the therapeutic effect of the puncture can be revealed. It can be attracted as evident method which is poor in risk for the confirmation of an indication to operation. This form of examination is possible also then, when no sonographic device with a puncture is at our disposal.

In 20 patients with a heavy overweight in the course of a fasting cure at 5 different moments gustation tests were carried out: in satiated state, in the acute fasting state and during the building-up phase. It could be proved that the thresholds in the acute fasting state are significantly lower than in the satiated state. Also in the building-up phase this tendency is pointed at. An efferent influence on the receptors evoked by hunger is discussed as cause. A direct relation between the change of the gustation sensitivity and individual metabolic parameters did, however, not develop under the experimental conditions given.

Macrosome newborns from mothers with an insulin-bound diabetes mellitus and also from mothers with a gestational diabetes show in the cord blood nearly always insulin levels additional to increased glucose values, which, compared with the normal controls are ten-fold higher in some cases. During the first three hours of life the blood glucose values decrease extremely. To prevent central injuries, caused by stronger hypoglycaemia, the early supply of oligosaccharides by continuous gastric infusion has proved as the most careful procedure. Stronger increases of blood glucose do not occur by this method and the insulin levels show a continuous tendency to normalisation.

It is reported on the possibilities of the application of anti-androgenics, especially of cyproterone acetate. The indication extends to hirsutism, sexual deviations, growth disturbances in pubertas praecox as well as diseases of the prostate. Particularly strong standard are to be applied in the treatment of fertile women, as there exists the danger of an intrauterine feminisation of male foetuses, when a pregnancy was not absolutely excluded. Side-effects and results of animal experiments are mentioned. The therapeutic mechanism of the anti-androgenics can be explained with the help of a concurrency mechanism at the androgen receptor or acceptor.

72 of 413 adults and 55 of 112 children with intact function of the hypophysis revealed secretions of the growth hormone already in the preparation time for a clinical test. These variations of the HGH basal levels must be regarded as conditioned on test. In the judgment of the function of the anterior lobe of the pituitary gland with the help of the dynamics of the HGH-secretion the changes in the pretest-period should be included in order to avoid false diagnoses. From the secretion of the growth hormone conditioned on stress hitherto no conclusions can be made to the following course of the HGH-secretion.

During pregnancy the thyroid is subjected to increased demands which is associated with a tendency to endogenous iodine deficiency. Under the conditions of insufficient iodine supply in the GDR the pathophysiological changes result in: 1. prevalence of goiter in about 60% of pregnant women; 2. enlargement of the extent of neck in more than 50% of all pregnant women examined only returning to the prepregnant status in 25%-40%; 3. prevalence of goiter in newborn with 5%; 12.8% of 1948 stilborn had macroscopically an enlarged thyroid gland, the highest weight being 45 g. More than 53% of the stilborn examined by autopsy had a thyroid weight of over 3 g; 4. in contrast to the regions with sufficient iodine supply renal iodine excretion was steadily decreasing during pregnancy and post partum, changing the iodine deficiency from grade II to grade III; 5. low iodine excretion in newborn: 1.3 +/- 0.2 microgram I/day in goitrous (1.2 +/- 0.2 nmol I/mmol creatinine) 2.2 +/- 0.4 micrograms I/day in non-goitrous (2.0 +/- 0.4 nmol I/mmol creatinine); 6. according to ETR more than 50% of the pregnant examined showed a hypothyroid tendency. The pathophysiological changes during pregnancy caused by insufficient iodine supply can be met efficiently by careful thyroid hormone treatment or by the administration of 150 micrograms I daily. A mandatory iodine salt prophylaxis is demanded.

In experiments with laboratory mice a desynchronisation of daily rhythms in plasma insulin concentration and feeding after inversion of the light-dark periodicity is documented. Whereas the feeding rhythm follows the exogenous Zeitgeber (differences concern above all the quantity of food which decrease after inversion), the acrophase of the hormone rhythm is stable in relation to astronomic time. The daily mean, however, is reduced and the main maximum is split into three components. The results support the hypothesis that rhythms of the two investigated parameters are generated by separate oscillators.

In 142 test persons the insulin hypoglycaemia test as well as the glucagon propranolol test were performed under the interrogation of a hyposomatotropism. The combination of these tests proved as suitable for the answers to this inquiry. The insulin hypoglycaemia test led in 29%, the propranolol glucagon test only in 6% to the false indication of a hyposomatotropism. Thus the propranolol glucagon test has the higher diagnostic certainty. Insulin hypoglycaemia test and propranolol glucagon test seem to have a different effect.