Radiopharmacokinetics and radiation dose from 99mTc-HM-PAO (Preliminary report)

Whole body retention measurements were performed in volunteers after i.v. injection of ^99mTc-HM-PAO (Ceretec^®). The organ accumulation was measured in mice and data were transferred to standard man according to ICRP. Absorbed dose calculations were made with these data by using the concept of absorbed fractions (MIRD method). In man, the whole body retention and the retention in the brain could be calculated by direct measurement, absorbed doses to the other organs could only be derived from animal data. The absorbed dose to the brain derived from human data (10.3 Gy/MBq) is greater by a factor of 2 than that derived from animal data. The highest absorbed dose was received by the thyroid (24.4 Gy/MBq), the absorbed dose to the ovaries, testes and whole body ranged from 2.8 to 4.2 Gy/MBq.Dedicated to Professor Dr. Guenter Liess on the occasion of his 65th anniversary     

Liver transplantation in a patient after COVID-19 – Rapid loss of antibodies and prolonged viral RNA shedding

To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA.     

Implications for farmers of measures to reduce sugars consumption

ObjectiveTo estimate the impact of reduced consumption of free sugars in line with World Health Organization recommendations, on sugar farmers globally.MethodsUsing multiregion input–output analysis, we estimated the proportional impact on production volumes of a 1% reduction in free sugars consumption by the public. We extracted data on sugar production from the Food and Agriculture Organization of the United Nations database for the top 15 sugar-cane- and beet-producing countries globally, and created a custom multiregion input–output database to assess the proportions of production going to human consumption, drawing on household expenditure surveys and national input–output databases (data valid for years 2000–2015). We also considered the impact on production volumes in relation to countries’ gross domestic product.FindingsA high proportion of current sugar production from these countries goes to human consumption, and would thus be impacted by reduced consumption of sugars. The largest impacts on cane sugar production, and thus on farmers, would likely occur in Brazil, China, India and Thailand and on beet production in Belarus, Germany, Russian Federation and United States of America.ConclusionA global opportunity exists for public health leadership to bring together the health, economic, environmental and agriculture sectors to collaborate and build capacity for promotion of alternative livelihoods for sugar farmers. Lessons regarding strategy and the importance of political economy factors can be learnt from tobacco control measures. Further research to quantify the impact of reductions in sugars consumption would provide useful insights for designing policies to complement and strengthen efforts to improve diets and health.     

Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53^+/−, p53^−/−) and Hd-rR HNI hybrid (p53^+/−) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53^+/− fish than in p53^−/− fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.     

Capillary neoformation in the rat heart-stereological studies on papillary muscles in hypertrophy and physiologic growth

Summary Stereological investigations on myocardial capillaries provided evidence that the common estimator of capillarity, the capillary density (i.c., number of capillary profiles per unit transverse sectional area), underestimates the true capillary supply since the capillary axes are not oriented perfectly in parallel to the myofiber axes. Recently, we studied the true capillarity, i.c., the length density of capillaries (L_v=capillary length per capillary volume), in some experimental models of cardiac hypertrophy which have been published elsewhere. It has been shown that L_v decreases in renovascular hypertension, but is maintained in physical exercise and after chronic thyroxin application. However, the growth pattern of capillaries in hypertrophic hearts has not yet been analyzed. In the present paper it is demonstrated that important information on the capillary network can be derived from the two-dimensional capillary-to-fiber ratios (2D CFR: capillary profiles per myofiber profiles in transverse sections) and from the three-dimensional capillary-to-fiber ratios (3D CFR: capillary length per unit myofiber length). Increase in both suggests neoformation of additional capillary branches in parallel connection. Retrospective analysis of the quantitative data indicates that in hypertrophy induced by physical exercise or by chronic thyroxin application capillary neoformation in parallel connection counterbalances increase of oxygen diffusion distance due to myofiber enlargement. In renovascular hypertension, capillary neoformation in parallel connection does not occur. Studies on normal growth indicated both a slight decrease of L_v of capillaries, as well as a continuous neoformation of additional capillary branches.     

Histamine H3 receptor-mediated inhibition of noradrenaline release in pig retina discs

Summary Discs of pig retina were preincubated with ³H-noradrenaline, ³H-dopamine or ³H-serotonin and then superfused. Electrical field stimulation increased the outflow of tritium from discs preincubated with ³H-noradrenaline or ³H-dopamine, but no from discs preincubated with ³H-serotonin. The tritium content at the end of superfusion was similar in discs preincubated with ³H-noradrenaline or ³H-dopamine but about tenfold lower in discs preincubated with ³H-serotonin. The tritium content in discs preincubated with ³H-noradrenaline was markedly reduced when desipramine was present during preincubation but was not affected by selective inhibitors of dopamine and serotonin uptake. The tritium content in discs preincubated with 3Hdopamine and ³H-serotonin, in contrast, was reduced or tended to be reduced by a selective dopamine and serotonin uptake inhibitor, respectively.The electrically evoked overflow of tritium from discs preincubated with ³H-noradrenaline was abolished by tetrodotoxin or omission of Ca²⁺. In discs superfused with desipramine, the electrically evoked overflow was enhanced by phentolamine but not affected by histamine. When both desipramine and phentolamine were present in the superfusion medium, histamine inhibited the evoked overflow (pIC₁₅ 6.85). This effect was mimicked by the histamine H₃ receptor agonist R-(–)--methylhistamine as well as by its S-(+)-enantiomer (pIC₁₅ 7.85 and 5.30, respectively) but not by the H₁ receptor agonist 2-(2-thiazolyl)ethylamine and the H₂ receptor agonist dimaprit (each 10 mol/l). The inhibitory effect of histamine was abolished by the H₃ receptor antagonist thioperamide 0.32 mol/l and attenuated by impromidine 3.2 mol/l but not affected by the H₁ receptor antagonist dimetindene 3.2 mol/l and the H₂ receptor antagonist ranitidine 10 mol/l.The results suggest that, in the pig retina, noradrenaline is taken up into, and released from, noradrenergic neurones (most likely vascular postganglionic sympathetic nerve fibres, less probably tissue-specific noradrenergic neurones of the retina) and that noradrenaline release is subject to modulation via H₃ receptors and probably also a-adrenoceptors.Send offprint requests to E. Schlicker at the above address     

Ifosfamide combination chemotherapy in advanced breast cancer

The objective of our clinical studies was to develop an effective combination chemotherapy regimen (CHT) with acceptable side effects, consisting of the two most potent drugs used as single agents in breast cancer. We tested the combination of an anthracycline, epirubicin (A) at 70 mg/m² i.v. on day 1 or (B) at 120 mg/m² i.v. on day 1 with an alkylating drug ifosfamide (IFO), (C) at 2.5 g/m² in an i.v. infusion given over 4 h on days 1–3 or (D) at 5 g/m² in a 24-h i.v. infusion given on day 1. Courses were repeated every 4 weeks. The combinations were given as first-line therapy as follows: CHT (A, C) in six cases and CHT (B, C) in five cases of advanced breast carcinoma, and CHT (B, D) in seven patients with primary inflammatory breast cancer. Due to side effects (e.g., stomatitis, mental disturbances) and applicability, CHT regimen (B, D) was preferred. Responses (12/18) occurred 1–3 cycles earlier than those previously achieved using the conventional epirubicin/cyclophosphamide CHT. We conclude that 5 g/m² IFO given i.v. over 24 h with uroprotection (mesna) in a two-drug regimen is an effective dose with tolerable toxicity. Alopecia was seen in all cases. However, according to our experience, myelotoxicity is the dose-limiting factor for both of these drugs.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Thermoresponsive Reversible Unimer Micelles of Amphiphilic Fluorinated Copolymers

Amphiphilic fluorinated copolymers PEGMAx-co-FAy and TEGMAx-co-FAy are prepared by activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). All polymers present a reversible thermoresponsive lower critical solution temperature-type behavior, and a cloud point temperature (T_c) in the range of 30–60 °C strictly dependent on the length of the oxyethylene side chain, the content of the hydrophobic counits, and the concentration of the solution. Combined small angle X-ray scattering (SAXS) and dynamic light scattering measurements are used to study the self-assembly behavior in water, organic solvents (tetrahydrofuran [THF] and dimethylformamide [DMF]), and a fluorinated solvent (hexafluorobenzene [HFB]). SAXS confirms the formation of compact-globular single-chain self-folded unimer micelles in water below T_c, which generally presents small hydrodynamic diameters (D_h ≤ 8 nm) as a result of the folding of the hydrophobic perfluorohexylethyl acrylate counits. The copolymers are also able to form reverse unimer micelle in HFB. The copolymers are not able to self-assemble in unimer micelles in THF or DMF solutions, in which they adopt conventional random coil conformations.     

Characterization of recast Nafion films by small- and wide-angle X-ray scattering

Room temperature recast Nafion

1 General formula:

films, prepared under different humidities in the curing atmosphere, were characterized by small- and wide-angle X-ray scattering (SAXS and WAXS). SAXS reveals that the humidity influences the size of the ionic clusters in these polymer films. It was found that the number and size of ionic clusters increases with increasing relative humidity. WAXS indicates the presence of locally ordered regions of the backbone polymer. These results allow a qualitative understanding of the electrochemical behaviour of Nafion recast films cured at different humidities, as described in the literature.