Solid-state dynamics and single-crystal to single-crystal structural transformations in octakis(3-chloropropyl)octasilsesquioxane and octavinyloctasilsesquioxane.

Reactive octahedral silsesquioxanes of rod-like [octakis(3-chloropropyl)octasilsesquioxane - T8(CH2CH2CH2Cl)8] and spherical [octavinyloctasilsesquioxane - T8(CH[double bond, length as m-dash]CH2)8] structure can undergo reversible thermally induced phase transitions in the solid state. The phase behaviour has been studied with differential scanning calorimetry (DSC, including temperature modulated DSC), X-ray diffraction, dielectric relaxation spectroscopy (DRS), and nuclear magnetic resonance spectroscopy in the solid state (SS NMR), as well as positron annihilation lifetime spectroscopy (PALS) and polarized optical microscopy (POM). The mechanisms involving fitting the molecules into most symmetrical crystal lattices vary for species of different structure. Thermal energy can be used to expand the crystal lattice leading to thermochromism in the case of T8(CH[double bond, length as m-dash]CH2)8 or conversely to an unusual negative thermal expansion of crystals of T8(CH2CH2CH2Cl)8 that results in their self-actuation. The complex behaviour is reflected in unusual changes in the capacitance and fractional free volume of the material. These phenomena can be used for molecular design of advanced well-defined hybrid materials capable of reversible thermally induced structural transformations. The findings present a new perspective for POSS-based flexible metal-organic frameworks (MOF) of cooperative structural transformability via entropy-based translational sub-net sliding.

Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers.

BACKGROUND AND AIMS: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. METHODS: Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients. RESULTS: The mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100 kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers. CONCLUSIONS: The variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others.

Drying Kinetics and Quality of Dehydrated Cranberries Pretreated by Traditional and Innovative Techniques.

The aim of this study was to analyze the impact of traditional and combined pretreatment on dehydration kinetics and quality of dried swamp cranberries. Fruits were blanched, cut, or treated by combined technique consisting of blanching and application of pulsed electric field. Afterwards, fruits were subjected for osmotic dehydration (OD; 72 hr) in 61.5% sucrose solution or in ternary solution consisting of 30% sucrose with 0.1% addition of steviol glycosides to ensure similar sweetness of both mixtures. In the case of samples treated by combined method, OD was enhanced during first 30 min by sonication. Partially dehydrated cranberries were air dried at 70 °C. The quality of dehydrated fruits was assessed by the means of phenolics content, anthocyanin content, flavonoid content, vitamin C content, water activity, and color. Blanching decreased drying time by 48% to 50% in comparison to cutting. Utilization of combined method reduced drying time of cranberries up to 55% in comparison to cut samples. Water activity of all samples was below 0.6. Blanched samples or blanched and then treated with pulsed electric field and ultrasound contained more anthocyanins and flavonoids and less sucrose than cut samples. PRACTICAL APPLICATION: According to current trends in food and beverage industry, consumers seek for products which does not contain excessive amounts of sugars, salt, or fats. Dried cranberry fruits are rich in bioactive compounds and need to be osmotically dehydrated in sugar solutions to make the taste of the final product acceptable. Osmotic dehydration is also carried out to decrease time of drying, which is one of the most energy intensive processes. Therefore, there is a need to develop a technology with potential to maintain the bioactive compounds, reduce sugar content in comparison to traditionally process fruits, and enhance the kinetics of drying.

Quality of life in noncompliant adults with phenylketonuria after resumption of the diet.

BACKGROUND: Discontinuation of dietary therapy in adults with phenylketonuria can lead to neuropsychological abnormalities and emotional problems. The aim of our study was to assess the change in quality of life in adult patients returning to the diet and to define the reasons for failure in diet resumption. METHODS: Quality of life was assessed by means of the Psychological General Well-Being Index before study entry and subsequently after 3 and 9 months. Reasons for failure in diet resumption were analysed. RESULTS: 53 patients participated in the study. Initial quality of life assessment revealed severe distress in 17%, moderate distress in 28% and positive well-being in 55% of them. In the majority of patients with severe or moderate distress, improvement of subjective well-being was observed (especially in the domains of anxiety and depressiveness) if they managed to return to the diet (blood phenylalanine concentrations before study entry 0.78-1.62 mmol/L, mean 1.16 mmol/L; average blood phenylalanine concentration decrease by 0.42 mmol/L). Only 29 persons managed to maintain the diet for at least 3 months and only 10 participants finished the entire 9-month study protocol. Problems with dietary treatment while at work, the high cost of low-protein products and poor knowledge regarding proper diet were the most important factors responsible for failure in resumption of diet. CONCLUSION: Interpersonal differences exist between adult patients on relaxed diet, in some of whom quality of life often remains good, while others can suffer from severe emotional distress. Returning to diet increases quality of life in the majority of patients.

Molecular modeling of singlet-oxygen binding to anthraquinones in relation to the peroxidating activity of antitumor anthraquinone drugs.

Anthraquinone derivatives are important anti-cancer drugs possessing, however, undesirable peroxidating and, in consequence, cardiotoxic properties. This results from the mediation by these compounds of the one-electron reduction processes of the oxygen molecule, which produces the highly toxic superoxide anion radical and other active oxygen species. This article summarizes the results of our studies on the molecular aspects of the mechanism of anthraquinone-mediated peroxidation which were carried out using enzymatic-assay, electrochemical, and quantum-mechanical methods.

Identification of Mutations Causing 6-Pyruvoyl- Tetrahydrobiopterin Synthase Deficiency in Polish Patients With Variant Hyperphenylalaninemia.

Background: 6-Pyruvoyl-tetrahydrobiopterin synthase (PTPS) is required for biosynthesis of tetrahydrobiopterin, the cofactor of various enzymes including the hepatic phenylalanine hydroxylase. Mutations in the PTS gene result in a variant type of hyperphenylalaninemia, requiring cofactor replacement therapy for treatment. Methods and Results: Four Polish patients with PTPS deficiency were screened for mutations in the PTS gene. Three novel mutations E35G, N36K, and F100V were identified. In one patient, a known mutation D136V was identified in both PTS alleles. Conclusions: Mutation D136V present in both alleles was proposed to be connected with a mild form of PTPS deficiency. The other three mutations were found in heterozygous patients with a central type of PTPS deficiency. D136V mutation is a common mutation in the Polish population.

Should newborn mutation scanning for hyperphenylalaninaemia and galactosaemia be implemented? A Polish experience.

OBJECTIVE: To elucidate whether screening for mutations causing hyperphenylalaninaemia (HPA) and classic galactosaemia could provide important, additional information on a clinical phenotype. METHOD: Genotypes that cause disease at the phenylalanine hydroxylase (PAH) gene and galactose-1-phosphate uridyltransferase (GALT) gene in a group of 101 hyperphenylalaninaemic and 77 patients with classic galactosaemia were established. The PAH and GALT mutations were identified in genomic DNA extracted from whole blood leucocytes using single stranded conformational analysis and direct fluorescent sequencing of polymerase chain reaction (PCR) products. RESULTS: Mild HPA and mild phenylketonurea (PKU) were caused by divergent genotypes. In the studied group a total of 26 different mild and intermediate PAH mutations were identified, most of them being rare ones. Classic galactosaemia was caused by two frequent mutations, accounting for 82% of all mutated alleles. CONCLUSIONS: Identification of mild or intermediate mutations causing HPA could provide fast and reliable information about future clinical outcome of a newborn infant. Molecular diagnosis of HPA should be preceded by biochemical analysis and implemented to differentiate mild forms of HPA and cases of ambiguous classification. Because of multiple rare mutations scattered on all exons, scanning of the entire PAH coding sequence could be useful and cost beneficial. Routine genotyping is not proposed in classic phenylketonuria and classic galactosaemia, as it provides limited additional, prospective information on the clinical phenotype.

Mutations in exon 3 of the PAH gene causing mild hyperphenylalaninemia.

Phenylketonuria (PKU), an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), is clinically very heterogeneous. On molecular level more than 350 mutations in the PAH gene are known to date, which in different genotype combinations could account for biochemical and clinical variability. Mutations located in exon 3 coding for a part of the regulatory domain of the PAH enzyme cause classical PKU, mild PKU, and mild hyperphenylalaninemia (MHP). We describe the phenotypic effects of seven mutations in exon 3 of the PAH gene (R68G, R68S, R71H, S87R, P89S, I95F, and A104D). We propose that mutations located between amino acid positions 71 through 94 cause MHP.

[Malonyldialdehyde, uric acid and white cell count as markers of oxidative stress in acute myocardial infarction and acute coronary insufficiency]. / Dwualdehyd malonowy, kwas moczowy i leukocytoza jako wykladniki stresu oksydacyjnego w swiezym zawale serca i ostrej niewydolnosci wiencowej.

UNLABELLED: Free radicals, produced in large amounts during myocardial ischemia and reperfusion, take part in the degradation of cellular and subcellular membrane structures. The source of oxygen radicals in the ischemic myocardium are neutrophils recruited into the necrotic region, as well as metabolic transformation of hypoxantine and xantine to uric acid. Subsequent reactions generate lipid peroxides and cytotoxic and-products of oxidation, among which is malondialdehyde (MDA). The aim of this study was to measure of MDA, uric acid and white cell count as markers of oxidative stress in patients with acute coronary insufficiency and acute myocardial infarction. We studied 75 participants (20 females and 55 males) aged 38-75, including 13 patients with acute myocardial insufficiency (group I: 6 females and 7 males, aged 40-66 years, mean 59.4 +/- 6.52), 40 patients with acute myocardial infarction (group II: 8 females and 32 males aged 38-72 years, mean 57.3 +/- 9.57) and 22 healthy volunteers (control group: 6 females and 16 males aged 39-75 years, mean 53.1 +/- 9.62). CONCLUSIONS: 1. Elevated levels of MDA in patients with acute myocardial infarction may reflect secondary disorders of cellular metabolism and late appearance of degradation products of lipid peroxides; 2. Uric acid may serve as an additional marker of free radical reactions in patients with acute myocardial infarction and acute coronary insufficiency.

Effect of ultrasound treatment on the water state in kiwifruit during osmotic dehydration.

The present work investigates how ultrasound pretreatment modulates the effects of osmotic dehydration (OD) on the water state and microstructure of kiwifruit. Kiwifruit slices (10mm thick) were subjected to ultrasonic waves in a water bath at a frequency of 35 kHz for 10, 20 and 30 min. OD process was then carried out by immersing the samples in 61.5% sucrose solution equilibrated at 25°C for a contact period of 0, 10, 20, 30, 60 and 120 min. The partition of water into the cellular tissue structures (vacuole, cytoplasm, extracellular spaces and cell wall) was investigated by Time Domain Nuclear Magnetic Resonance (TD-NMR). In parallel, the microstructure of kiwifruits slices was examined using a Scanning Electron Microscope. The results showed that US pretreatment performed for more than 10 min had a positive effect on the mass exchange caused by osmotic dehydration. A creation of microchannels and an increase of the average cross-section area of cells were observed when the samples were pretreated with US before OD. TD-NMR showed a slight redistribution of water through the substructures of the cells, as a function of the length of the US pretreatment applied.

Blood phenylalanine control in phenylketonuria: a survey of 10 European centres.

BACKGROUND: Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet. OBJECTIVE: A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in 10 European centres. METHODS: Centres experienced in the management of PKU from Belgium, Denmark, Germany, Italy, The Netherlands, Norway, Poland, Spain, Turkey and the United Kingdom provided retrospective audit data of all patients with PKU treated by diet over a 1-year period. Standard questions were used to collect median data on blood Phe concentrations, percentage of blood Phe concentrations below upper target reference ranges and frequency of blood Phe sampling. RESULTS: Data from 1921 patients on dietary management were included. Blood Phe concentrations were well controlled and comparable across centres in the early years of life. The percentages of blood Phe concentrations meeting each centre's local and national target ranges were 88% in children aged up to 1 year, 74% for 1-10 years, 89% for 11-16 years and 65% for adults (>16 years). The frequency of home blood sampling, compared with local and national recommendations for monitoring Phe concentrations, appeared to decline with age (from approximately 100% in infancy to 83% in teenagers and 55% in adults). CONCLUSIONS: Although blood Phe control generally deteriorated with age, some improvement was observed in adolescent years across the 10 European centres. The blood Phe control achieved seemed comparable in many of the European centres irrespective of different dietary treatments or national policies.

HLA-B27 is a potential risk factor for posttransplantation diabetes mellitus in autosomal dominant polycystic kidney disease patients.

The aim of this work was to investigate HLA phenotype predisposition to posttransplantation diabetes mellitus (PTDM) in kidney transplant recipients stratified according to kidney failure etiology. Ninety-eight transplant recipient pairs with kidney grafts from the same cadaveric donor were qualified for the study. In each pair, 1 kidney was grafted to an individual with autosomal dominant polycystic kidney disease (ADPKD group) and 1 to recipient with a different cause of kidney failure (non-ADPKD group). All class II HLA antigens were determined with the PCR-SSP molecular method. To identify class I HLA molecules we used both molecular and serologic methods. Diabetes was diagnosed according to the American Diabetes Association criteria. The posttransplantation observation period was 12 months. In the ADPKD group, HLA-B27 was more common in PTDM than non-PTDM patients; 31.6% versus 11.4% (P = .069). The difference achieved significance when comparing insulin-treated with non-insulin-treated patients (44.4% vs 12.4%; P = .029). In the non-ADPKD group, HLA-A28 and HLA-B13 were observed more frequently in patients with PTDM than in recipients without diabetes (22.2% vs 2.5% [P = .0099] and 22.2% vs 3.8% [P = .020]). All of these associations were significant upon multivariate analysis. HLA-B27 allele is a factor predisposing ADPKD patients to insulin-dependent PTDM. Antigens predisposing to PTDM among kidney graft recipients without ADPKD include HLA-A28 and B13.

Use of handheld computers for assessment of prefrontal cortex function in patients with phenylketonuria.

Assessment of prefrontal brain cortex function can be helpful in treatment monitoring in patients with phenylketonuria. We aimed to assess the usefulness of computerized neuropsychological tests developed for handheld computers for this purpose. We observed worse test performance among persons with blood phenylalanine concentrations exceeding the recommended range. Use of handheld computers was assessed by patients and by doctors as interesting, not time-consuming and convenient. This method can be helpful during routine follow-up visits.

Effect of exposure to cold and fasting on the placental glycogen and triglyceride content in the rat.

The effect of exposure to cold (+2 degrees C, 3 and 24 h) and fasting (1, 2 and 3 days) on placental glycogen and triglyceride content was investigated in rats pregnant for 20 days. The stimuli did not affect the level of glycogen in the placenta. The level of triglycerides remained unchanged in the rats exposed to cold. It rose after only one day of fasting and then levelled out on the 2nd and 3rd days. Fasting, but not exposure to cold produced hypoglycemia and elevation of the plasma free fatty acids level. We conclude that activation of the adrenergic system during exposure to cold does not interfere with the glycogen and triglyceride content of the placenta. Prolonged hypoglycemia also does not affect the placental glycogen level although it increases the accumulation of neutral fat.

Metabolic response to starvation in late pregnant rats. II. Fetal response.

Effect of prolonged maternal fasting on the fetal liver and heart glycogen and triglyceride content and on concentration of glucose, urea, uric acid and alpha amino-nitrogen in the amniotic fluid has been studied in rats. The animals were divided into four groups: fed (control), fasted for one day (from 20 to 21 day of pregnancy), fasted for two days (from 19 to 21 day) and fasted for three days (from 18 to 21 day). Maternal fasting for two and three days resulted in reduction in fetal growth. The fetal liver glycogen content was reduced already after one day of fasting, stabilized after two days and then further decreased after three days. The fetal heart glycogen content was reduced only after three days of fasting. The fetal liver triglyceride content increased gradually during the first two days of fasting and then stabilized. The content of triglycerides in the heart was elevated after two and three days of food deprivation. The amniotic fluid glucose concentration decreased after one day of fasting and then stabilized. Fasting did not effect the concentration of the nitrogenous compounds in the amniotic fluid. It is concluded that maternal fasting affects markedly metabolism of energy substrates stored in the fetal liver and the heart and the composition of the amniotic fluid.

Metabolic response to starvation in late pregnant rats. I. Maternal response.

The aim of the present study was to examine effect of prolonged fasting on muscle glycogen and triglyceride concentration as well as on non-protein nitrogen excretion with urine in late pregnant rats. They were divided into four groups: I--fed, pregnant for 21 days, II--fasted for one day (from 20 to 21 day of pregnancy), III--fasted for two days (from 19 to 21 day) and IV--fasted for three days (from 18 to 21 day). The concentration of glycogen and triglycerides was determined in the following tissues: the white and red layers of the vastus lateralis, the soleus, the diaphragm, the heart and the liver. The urine was collected in each group 24 h (from 20 to 21 day). It has been found that concentration of glycogen in the leg muscles is reduced by about 50% and in the diaphragm by 75% already after 24 h fasting and then remains stable. The concentration of glycogen in the heart increases after one day of fasting and then returns to the control value. The effect of fasting on the concentration of triglycerides in the tissues depends on a tissue studied. It decreases gradually in the white vastus, and in the soleus only on the third day. It is elevated during the first two days of fasting in the red vastus, diaphragm and liver and returns to the control level on the third day. The fasting doubled the concentration of triglycerides in the heart. The urinary urea, creatinine, and uric acid excretion decreases and ammonia excretion increases during fasting. The results obtained indicate that the late gestation does not alter response of muscle glycogen metabolism to fasting as compared to the male rats. It does effect metabolism of triglycerides.