Experiences of a multistep process with medical and psychological interventions for patients with congenital uterine aplasia to achieve motherhood: the Gothenburg-Tübingen collaboration.

Congenital uterine aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a condition associated to a non-functional uterus in the presence of functional ovaries. In a setting where surrogacy is illegal (or not accepted) and adoption is the only alternative, neovaginoplasty and subsequent uterus transplantation (UTx) can provide a route to motherhood for women with MRKHS. This review article describes a multistep process by which patients with MRKHS can achieve motherhood with their own biological child. This process involving a careful clinical diagnosis, psychological counselling, assessment of eligibility for neovagina creation and UTx, the surgical treatment, fertility treatment, and long-term follow-up was developed at the Tübingen University Hospital and in close collaboration with Sahlgrenska Academy, University of Gothenburg, Sweden, where the basic experimental and clinical groundwork for UTx was laid and the first-ever UTx procedure was performed.

Neovagina creation methods and their potential impact on subsequent uterus transplantation: a review.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation.

Tailoring fatty food simulants made from solvent mixtures (2): determining the equivalent migration behaviour of olive oil and of solvents in the case of polyolefins.

It is suggested that solvent mixtures consisting of an ester and of an inert solvent can be used as fatty food simulants capable of having the same migration behaviour as olive oil with plastics. Migration tests carried out with low-density polyethylene for 20 and 48 h in an 8 and 5% mixture of tert-butyl acetate in ethanol respectively gave results equivalent to those obtained with olive oil after 10 days at 40 degrees C. The use of solvent mixtures facilitated the analysis and improved detection limits, giving good repeatability. Furthermore, the more rapid migration in solvent mixtures can be particularly useful for industrial controls as alternative test methods.

Safety and quality of food contact materials. Part 1: evaluation of analytical strategies to introduce migration testing into good manufacturing practice.

The results of a research project (EU AIR Research Programme CT94-1025) aimed to introduce control of migration into good manufacturing practice and into enforcement work are reported. Representative polymer classes were defined on the basis of chemical structure, technological function, migration behaviour and market share. These classes were characterized by analytical methods. Analytical techniques were investigated for identification of potential migrants. High-temperature gas chromatography was shown to be a powerful method and 1H-magnetic resonance provided a convenient fingerprint of plastic materials. Volatile compounds were characterized by headspace techniques, where it was shown to be essential to differentiate volatile compounds desorbed from those generated during the thermal desorption itself. For metal trace analysis, microwave mineralization followed by atomic absorption was employed. These different techniques were introduced into a systematic testing scheme that is envisaged as being suitable both for industrial control and for enforcement laboratories. Guidelines will be proposed in the second part of this paper.

Alternative test methods to control the compliance of polyolefin food packaging materials with the European Union regulation: the case of aromatic antioxidants and of bis(ethanolamine) antistatics based on 1H-NMR and UV-visible spectrophotometry.

In order to decide whether a plastic food packaging material complies with the European Communities (EC) regulation on migration, a quick analysis of two functional classes of plastics additives (aromatic antioxidants and antistatic agents) from polyolefin materials by 1H-NMR and UV-visible spectrophotometry is presented. The scope of spectroscopic methods for alternative and migration tests is presented. 1H-NMR can be used in several ways, from a simple fingerprint of the potential migrants to an identification procedure. Extraction is optimized using UV spectrophotometry. Optimization relies on extraction kinetics, which include the demonstration that extraction is more severe than migration. Only a few hours are required to conclude whether a material complies with the regulation. The specific migration limits are expressed as specific absorbance limit values, alpha. These data can be annexed by food industries to specifications of a plastic packaging material.

Quick methods to control compliance of plastic materials with food packaging regulations.

A general strategy is presented, aiming to provide plastics manufacturers, food industries and enforcement laboratories with quick methods to check whether migration from materials for food contact will be acceptable during the time of use. The strategy involves several steps, with increasing time demand and cost. Monitoring extraction kinetics allows both the optimization of the extraction time, and the selection of conditions where extraction is more severe than migration. The influence of the extracting solvent is discussed. It may give rise to specific non-extraction of some migrants, which may change the conclusions when the solvent is used in replacement of a fatty food simulant. Factors ruling this effect at a given temperature are identified: the affinity to the solvent with the migrant (selectivity), its ability to reach molecules entangled in the polymeric network (accessibility) and its interaction with the polymer (penetration). The kinetic parameters of the penetration of olive oil into polypropylene have been determined by the determination of profiles of concentration.

Guidelines of the Commission of the European Communities: a challenge for the control of packaging.

Questions arising from the Commission of the European Communities Directives and guidelines regulating packaging materials are discussed in relation to whether compliance ensures safety in use and the consequent analytical problems. Difficulties may arise from interactions between food contact materials and food involving mass transfer (migration, off-odours, 'scalping', loss of aroma) or mass transfer and chemical interactions and the implications for safety assurance and regulation are addressed. The criteria for suitable low molecular weight fatty food simulants and conditions for migration testing are presented. In food surveillance, the usefulness of various methods of analysis differs for monomers and for additives. For monomers, IR spectroscopy can identify the polymer type and which specific monomers need controlling; for unknown mixtures of additives, preliminary functional group identification by techniques such as 1H-NMR is useful.

1H-NMR for the safety control of food packaging materials: analysis of extracts from polyolefin samples.

A new approach for the identification of the additives in extracts of packaging plastics, using proton nuclear magnetic resonance (1H-NMR), is presented. The technique can be used in a preliminary step for the determination of contaminants potentially released by the food packaging materials; it may greatly reduce the time required to identify the constituents of the materials, either individually or as functional classes. A classification of the EEC additives is proposed on the basis of chemical shift. 1H-NMR can also be used as a fingerprint technique in the quality control of the food packaging materials.

Differential scanning calorimetry of Cu,Zn-superoxide dismutase, the apoprotein, and its zinc-substituted derivatives.

We have employed differential scanning calorimetry (DSC) to investigate the thermally induced unfolding of native Cu,Zn-superoxide dismutase (SOD), the apoprotein derived from native SOD, and the zinc-substituted derivatives of the apoprotein. We observe two overlapping melting transitions for native bovine SOD with heat capacity maxima at temperatures (Tm) of 89 and 96 degrees C when a scanning rate of 0.82 deg/min is employed. By contrast, the dithionite-reduced native SOD (which contains Cu+ rather than Cu2+) exhibits only a single transition at 96 degrees C. Significantly, we find that the concentration of O2 present in native SOD samples influences the relative magnitudes of the 89 and 96 degrees C peaks. Specifically, the lower temperature transition becomes less pronounced as the concentration of O2 in the sample decreases. On the basis of these observations, we propose that the lower temperature peak corresponds to the melting of the oxidized native protein, while the higher temperature peak reflects the melting of the reduced native protein, which forms spontaneously during the heating process. Our interpretation profoundly differs from that of Lepock et al. [Lepock, J.R., Arnold, L.D., Torrie, B.H., Andrews, B., & Kruuv, J. (1985) Arch. Biochem. Biophys. 241, 243-251], who have proposed that the low-temperature transition corresponds to the reduced form of the protein. We present evidence that suggests that their experiments were complicated by the presence of potassium ferrocyanide, which, in addition to reducing the cupric center, also perturbs the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

The increase in skin 7-dehydrocholesterol induced by an hypocholesterolemic agent is associated with elevated 25-hydroxyvitamin D3 plasma level.

Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N'-(2-chlorophenyl)-N-piperazinyl-1- [propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05 +/- 0.20; HCG 917, 0.3 mg/kg: 1.41 +/- 0.22; HCG 917, 5.0 mg/kg: 2.35 +/- 0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2 +/- 2.2; HCG 917 5.0 mg/kg: 57.6 +/- 6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism.

Resonance Raman and EPR of nitrosyl human hemoglobin and chains, carp hemoglobin, and model compounds. Implications for the nitrosyl heme coordination state.

We report the joint resonance Raman (RR) and electron paramagnetic resonance (epr) study of five- and six-coordinate nitrosyl heme model compounds and of the titled nitrosyl hemoproteins. Both epr and RR spectra fall into two types which, in the models, correspond to five- and six-coordinate nitrosyl hemes. However, neither RR nor epr spectroscopy is highly sensitive to the nature of the bond between a nitrosyl heme and a coordinated nitrogenous base, nor do the results of one technique uniformly correlate with those of the other. It is not possible to use epr spectroscopy as a test for the coordination state of a nitrosyl heme. The position of the highest frequency (depolarized) RR band possibly provides such a test. Any breaking of the very weak bond between nitrosyl heme and proximal histidine in T state human HbNO is more a consequence of tertiary structural features unique to the human alphaNO chains than it is of properties of the T quaternary conformation.

Tertiary structure variability within the quaternary states of hemoglobin: a spin label study.

Using variable temperature techniques, the spin label spectral resolution of hemoglobin labeled at the beta93 cysteines with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodonacetamide has been greatly enhanced. The effects of different ligands, inositol hexaphosphate, pH and salt concentration upon spin labeled ferrous and ferric hemoglobin indicate that the beta chain tertiary structure exhibits considerable variability within the oxy and deoxy quaternary structures. From these studies ligand and spin state changes both appear to be of significance in producing structural changes; binding of inositol hexaphosphate then produces further structural changes secondary in amplitude.