Differential changes to splanchnic and peripheral protein metabolism during the diet-induced development of metabolic syndrome in rats.

Little is known about the effects of the development of metabolic syndrome (MS) on protein and amino acid (AA) metabolism. During this study, we took advantage of the variability in interindividual susceptibility to high fat diet-induced MS to study the relationships between MS, protein synthesis, and AA catabolism in multiple tissues in rats. After 4 mo of high-fat feeding, an MS score (ZMS) was calculated as the average of the z-scores for individual MS components [weight, adiposities, homeostasis model for the assessment of insulin resistance (HOMA-IR), and triglycerides]. In the small intestine, liver, plasma, kidneys, heart, and muscles, tissue protein synthesis was measured by 2H2O labeling, and we evaluated the proportion of tissue AA catabolism (relative to protein synthesis) and nutrient routing to nonindispensable AAs in tissue proteins using natural nitrogen and carbon isotopic distances between tissue proteins and nutrients (Δ15N and Δ13C), respectively. In the liver, protein mass and synthesis increased, whereas the proportion of AA catabolism decreased with ZMS. By contrast, in muscles, we found no association between ZMS and protein mass, protein synthesis (except for a weak positive association in the gastrocnemius muscle only), and proportion of AA catabolism. The development of MS was also associated with altered metabolic flexibility and fatty acid oxidation, as shown by less routing of dietary lipids to nonindispensable AA synthesis in liver and muscle. In conclusion, MS development is associated with a greater gain of both fat and protein masses, with higher protein anabolism that mainly occurs in the liver, whereas muscles probably develop anabolic resistance due to insulin resistance.

Simulation of H p (10) and effective dose received by the medical staff in interventional radiology procedures.

Interventional radiology and cardiology are widespread employed techniques for diagnosis and treatment of several pathologies because they avoid the majority of the side-effects associated with surgical treatments, but are known to increase the radiation exposure to patient and operators. In recent years many studies treated the exposure of the operators performing cardiological procedures. The aim of this work is to study the exposure condition of the medical staff in some selected interventional radiology procedures. The Monte Carlo simulations have been employed with anthropomorphic mathematical phantoms reproducing the irradiation scenario of the medical staff with two operators and the patient. A personal dosemeter, put on apron, was modelled for comparison with measurements performed in hospitals, done with electronic dosemeters, in a reduced number of interventional radiology practices. Within the limits associated to the use of numerical anthropomorphic models to mimic a complex interventional procedure, the personal dose equivalent, H p (10), was evaluated and normalised to the simulated Kerma-Area Product, KAP, value, indeed the effective dose has been calculated. The H p (10)/KAPvalue of the first operator is about 10 µSv/Gy.cm2, when ceiling shielding is not used. This value is calculated on the trunk and it varies of +/-30% moving the dosemeter to the waist or to the neck. The effective dose, normalised to the KAP value, varies between 0.03 and 0.4 µSv/Gy.cm2. Considering all the unavoidable approximation of this kind of investigations, the comparisons with hospital measurement and literature data showed a good agreement allowing to use of the present results for dosimetric characterisation of interventional radiology procedures.

A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients.

CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late asthmatic response (LAR) to inhaled allergen at screening were randomised to receive CHF6001 400 µg or 1200 µg or placebo administered once a day using a dry powder inhaler. The three treatment periods were 9 days; allergen challenges were performed on day 9 and induced sputum was obtained after 10 h from challenge. Washout periods between treatments were up to 5 weeks. Both CHF6001 doses significantly attenuated the LAR; the primary endpoint analysis showed that CHF6001 400 µg and 1200 µg caused reductions of 19.7% (p = 0.015) and 28.2% (p < 0.001) respectively of the weighted FEV1 AUC4-10h compared with placebo. The difference between the CHF6001 doses was not statistically significant (p = 0.223). Compared with placebo, CHF6001 caused greater reduction in sputum eosinophil counts, although these changes were not statistically significant. CHF6001 was well tolerated, with similar numbers of adverse events in each treatment period. This inhaled PDE4 inhibitor has the potential to provide clinical benefits in patients with atopic asthma.

First results of an eye lens dosimetry survey in an interventional cardiology department.

The eye lens annual dose limit for exposed personnel to ionizing radiation has recently been revised by the ICRP--International Commission on Radiological Protection and the proposed new limit has been accepted by European legislation through the Council Directive 2013/59/EURATOM 2013. Among medical exposed personnel, the staff performing interventional cardiology are usually affected by relevant doses. For this reason a survey, employing dosemeters characterized in terms of H(p)(3), was performed in order to get the order of magnitude of the doses received by the eye lens, at least as a first guess.The survey showed that the annual dose limit can easily be reached if a proper radiation protection approach is not implemented.

A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content.

BACKGROUND AND AIMS: Fish, especially fatty fish, are the main contributor to eicosapentaenoic (EPA) and docosahexaenoic (DHA) intake. EPA and DHA concentrations in red blood cells (RBC) has been proposed as a cardiovascular risk factor, with <4% and >8% associated with the lowest and greatest protection, respectively. The relationship between high fat fish (HFF) intake and RBC EPA + DHA content has been little investigated on a wide range of fish intake, and may be non-linear. We aimed to study the shape of this relationship among high seafood consumers. METHODS AND RESULTS: Seafood consumption records and blood were collected from 384 French heavy seafood consumers and EPA and DHA were measured in RBC. A multivariate linear regression was performed using restricted cubic splines to consider potential non-linear associations. Thirty-six percent of subjects had an RBC EPA + DHA content lower than 4% and only 5% exceeded 8%. HFF consumption was significantly associated with RBC EPA + DHA content (P [overall association] = 0.021) adjusted for sex, tobacco status, study area, socioeconomic status, age, alcohol, other seafood, meat, and meat product intakes. This relationship was non-linear: for intakes higher than 200 g/wk, EPA + DHA content tended to stagnate. Tobacco status and fish contaminants were negatively associated with RBC EPA + DHA content. CONCLUSION: Because of the saturation for high intakes, and accounting for the concern with exposure to trace element contaminants, intake not exceeding 200 g should be considered.

ON THE PLACEMENT OF APRON DOSEMETERS AND DOSE ASSESSMENT IN INTERVENTIONAL CARDIOLOGY PROCEDURES: PRELIMINARY RESULTS.

Personnel involved in interventional practices are likely to be exposed to higher radiation doses than other workers in the medical field. Personnel monitoring and radiation protection measures play a crucial role in keeping these doses below the limits. EURADOS (European Radiation Dosimetry Group) Working Group 12 performed a series of investigations showing how the complexity of the scattered field reaching the operators can influence the doses to the operators. The present work was aimed at determining the possible effects on the registered doses of the scattered field and the actual position of a dosemeter on apron. This study has been performed through Monte Carlo simulations and it was validated through measurements. It does not claim to identify the 'best' position for the dosemeter, but to assess the variability of its response, showing how a variability of the order of +/- 30% to 40 should be taken into account.

Reconstruction of the pelvic ring in iliac or iliosacral resections: allograft or autograft?

BACKGROUND: The necessity to reconstruct the pelvic ring after an iliac or iliosacral resection is still debated. Different reconstructive techniques are available, including autologous and homologous graft and custom-made prosthesis. The aim of this study was to evaluate the functional outcome and complications of patients who underwent resection of iliac bone and part of the sacrum for primary bone tumour and reconstruction with an allograft or autograft. METHODS: We retrospectively evaluated 18 patients (10 males and 8 female) with a mean age of 28 years (range 9-56) who were operated between 1992 and 2015. Six patients were reconstructed with an autograft (Group A) and 12 patients with an allograft (Group B). All complications were recorded. At final follow-up, patients with the original reconstruction still in site were functionally evaluated with MSTS Score. RESULTS: Mean follow-up time was 107 months (range 4-221). Two patients (11.1%) had an external hemipelvectomy for local recurrence, and 3 patients died of the disease. Mean MSTS Score was comparable between the two groups 21.7 (range 20-25) in Group A and 19.9 (range 4-28) in Group B. Patients with partial sacral resection had an increased risk of local recurrence and lower MSTS Score [15.5 (range 7-20) vs. 22.2 (range 4-28)]. CONCLUSIONS: Biological reconstruction of pelvic ring with autologous or homologous bone graft gives acceptable functional results. However, the decision on how to reconstruct the pelvic ring after iliac resection should be taken on a patient-by-patient basis.

Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28.

Immune checkpoint inhibitors have revolutionized cancer therapy leading to exceptional success. However, there is still the need to improve their efficacy in non-responder patients. Natural killer (NK) cells represent the first line of defence against tumours, due to their ability to release immunomodulatory cytokines and kill target cells that have undergone malignant transformation. Harnessing NK cell response will open new possibilities to improve control of tumour growth. In this respect inhibitory checkpoints expressed on these innate lymphocytes represents a promising target for next-generation immunotherapy. In this review, we will summarize recent evidences on the expression of NK cells receptors in cancer, with a focus on the inhibitory checkpoint programmed cell death protein 1 (PD-1). We will also highlight the strength and limitations of the blockade of PD-1 inhibitory pathway and suggest new combination strategies that may help to unleash more efficiently NK cell anti-tumour response.

Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences.

Depending on the amount of alimentary proteins, between 6 and 18 g nitrogenous material per day enter the large intestine lumen through the ileocaecal junction. This material is used as substrates by the flora resulting eventually in the presence of a complex mixture of metabolites including ammonia, hydrogen sulfide, short and branched-chain fatty acids, amines; phenolic, indolic and N-nitroso compounds. The beneficial versus deleterious effects of these compounds on the colonic epithelium depend on parameters such as their luminal concentrations, the duration of the colonic stasis, the detoxication capacity of epithelial cells in response to increase of metabolite concentrations, the cellular metabolic utilization of these metabolites as well as their effects on colonocyte intermediary and oxidative metabolism. Furthermore, the effects of metabolites on electrolyte movements through the colonic epithelium must as well be taken into consideration for such an evaluation. The situation is further complicated by the fact that other non-nitrogenous compounds are believed to interfere with these various phenomenons. Finally, the pathological consequences of the presence of excessive concentrations of these compounds are related to the short- and, most important, long-term effects of these compounds on the rapid colonic epithelium renewing and homeostasis.

The ENEA neutron personal dosimetry service.

The ENEA Radiation Protection Institute has been operating the only neutron personal dosimetry service in Italy since the 1970s. Since the 1980s the service has been based on PADC (poly allyl diglycol carbonate) for fast neutron dosimetry, while thermal neutron dosimetry has been performed using thermoluminescence (TL) dosemeters. Since the service was started, a number of aspects have undergone evolution. The latest and most important changes are as follows: in 1998 a new PADC material was introduced in routine, since 2001 TL thermal dosimetry has been based on LiF(Mg,Cu,P) [GR-200] and (7)LiF(Mg,Cu,P) [GR-207] detectors and since 2003 a new image analysis reading system for the fast neutron dosemeters has been used. Herein an updated summary of how the service operates and performs today is presented. The approaches to calibration and traceability to estimate the quantity of H(p)(10) are mentioned. Results obtained at the performance test of dosimetric services in the EU member states and Switzerland sponsored by the European Commission and organised by Eurados in 1999 are reported. Last but not least, quality assurance (QA) procedures introduced in the routine operation to track the whole process of dose evaluation (i.e. plastic QA, acceptance test, test etching bath reproducibility and 'dummy customer' (blind test) for each issuing monitoring period) are presented and discussed.

Batch homogeneity of LiF(Mg,Cu,P)-GR200 and LiF(Mg,Cu,P)-MCP-NS TL detectors for use as extremity dosemeters at ENEA personal dosimetry service.

The results of a study of two commercially available LiF(Mg,Cu,P) TL materials, a GR200 detector and a MCP-Ns thin detector, are described in order to use these phosphors for individual monitoring for the extremities. After a dosimetry system has been type tested, the implementation routine is not straightforward. Additional tests and software modification are needed to make the routine system work comply with the type test results. Not often can literature be found on the steps required to implement the results in a routine study. This paper reports the results of the individual calibration of about 15 000 extremity dosemeters, 12 000 containing a GR200 detector and 3000 an MCP-Ns thin detector. It describes the experimental procedure followed in order to assure reproducibility and stability of the results with proper accuracy and reliability. In particular, this is the first time that results on homogeneity of such a large batch of MCP-Ns detectors are reported.

The implementation in routine of the ENEA new personal photon dosemeter.

The ENEA photon dosemeter, introduced in 1995, consisting of two differently filtrated LiF(Mg,Cu,P) detectors, has been modified recently. The ABS (acrylonitrile butadiene styrene) plastic support has been replaced by a new aluminium card supporting the same two detectors (LiF(Mg,Cu,P) GR200). The new card, fully developed at the ENEA-Radiation Protection Institute (which is going to be patented), can now be processed through a Harshaw Model 6600 Automated TLD Reader, a hot gas reader. This paper reports the results of the individual calibration of approximately 60,000 LiF(Mg,Cu,P) GR200 detectors inserted on the new aluminium cards. Before the implementation in routine of the new cards, the reader has been characterised. Steps and tests to be made to use the card in routine (i.e. reader stability, linearity, reproducibility, etc.) are reported. The whole dosimetric system now combines the very good performances of the Harshaw Model 6600 reader and that of LiF(Mg,Cu,P) thermoluminescent material.

Atypical onset of antiphospholipid syndrome in pregnancy: a case report.

BACKGROUND: We present a case of an atypical onset of antiphospholipid syndrome (APS). CASE: A woman in her 15th week gestation had a thrombosis of an unknown cerebral cavernoma, which was successfully removed. Twenty-six days after, she was admitted for a severe pain in right hypochondrium and a second class HELLP syndrome was diagnosed. Two days after, she had a fetal loss. After 1 month, laboratory tests revealed high level of antiphospholipid antibodies. At the same time, she developed a spontaneous thrombosis at her right arm. After 6 weeks, antiphospholipid antibodies, tested again, result positive. CONCLUSION: Antiphospholipid antibodies often cause pregnancy complications, but, to our knowledge, this is the first report of an association of antiphospholipid antibodies, with cerebral cavernoma thrombosis and early onset HELLP syndrome.

Great vessels transposition and aortic arch exclusion.

AIM: We describe our experience in endovascular repair of Thoracic Aortic Aneurysms and Dissections (TAAD) involving the aortic arch in high risk patients (HRP). METHODS: Twenty-nine patients presented with TAAD involving the aortic arch and were treated by endovascular exclusion. Pathologies were as follows: atherosclerotic aneurysms of the descending thoracic aorta in 15 cases, acute Stanford type A dissections in 6 cases, Stanford type B dissections in 7 cases (1 acute), and 1 false aneurysm of the ascending aorta. Total-arch transpositions of all supra-aortic vessels (aortic debranching) to the ascending aorta were done in 11 cases throught median sternotomy. We performed carotido-carotid bypass (hemi-arch transposition) in 16 patients by cervicotomy. Secondary to surgical transpositions, we placed endovascular stentgrafts in all but 2 patients for final exclusion, the 2 remaining being planned for later exclusion. The Talent, Excluder, TAG and Zenith endografts were used in 12, 3, 1 and 4 cases respectively. Banding technique was associated in some cases. RESULTS: All surgical transpositions were successful although 1 led to a minor stroke (1/29=3.5%), which worsened to major stroke after endovascular exclusion. Endovascular procedures were performed in all but one case (26/27=96.3%). Two patients (2/26=7.7%) died from catheterization related complications after endovascular exclusion (iliac rupture and left ventricle perforation). One patient had a delayed minor stroke (1/26=3.8%). Recirculation was found in 13.3% (2/15) of aneurysms and 27.3% of thoracic false channels. During a mean follow-up of 15.7 months (13 days to 45.5 months), 1 patient (1/26=3.8%) who had preoperative chronic pulmonary failure died at 6 months from respiratory worsening. We observed one case (3.8%) of unilateral limb palsy unrelated to cerebral ischemia, which we successfully treated by cerebrospinal fluid (CSF) drainage. No stent-related complication was seen. One new type 1 endoleak appeared at 12 months on an aneurysm, which resolved after stentgraft extension. Three thoracic dissection false channels remained patent during follow-up, of which one was retrograde originating distally in the descending aorta. CONCLUSIONS: Secondary endovascular exclusion of thoracic aortic diseases involving the arch in HRP is made feasible thanks to the preliminary aortic debranching. Total-arch transposition may be of greater interest in case of proximal neck length uncertainty and potential embolization from the aortic arch. Mid-term results are good although patients must be followed carefully to detect aortic recirculation and enlargement.

Biosynthetic origin of syringomycin and syringopeptin 22, toxic secondary metabolites of the phytopathogenic bacterium Pseudomonas syringae pv. syringae.

The biosynthesis of syringomycin (SR) and syringopeptin 22 (SP22), bioactive lipodepsipeptides of the phytopathogenic bacterium Pseudomonas syringae pv. syringae, was studied by feeding (14)C-labeled precursors to chloramphenicol-containing bacterial suspensions. The preferential sites of incorporation were determined by comparing the specific activities of the intact radiolabeled metabolites and their single structural elements, obtained by hydrolytic degradation followed by derivatization and isolation by high performance liquid chromatography. The results show that, upon feeding L-[(14)C(U)]-Thr, 35.0 and 31.0% of the SR radioactivity is retained in 2,3-dehydro-2-aminobutyric acid (Dhb) and 4-chlorothreonine (Thr(4-Cl)), respectively. L-[(14)C(U)]-Asp labels the same sites, though less efficiently, and is also incorporated in 2,4-diaminobutyric acid (Dab) and 3-hydroxyaspartic acid (Asp(3-OH)). Dhb is also labeled by Thr and Asp in SP22. These are the first data on the biosynthetic origin of the modified residues in P. syringae lipopeptides.

Guar gum does not impair the absorption and utilization of dietary nitrogen but affects early endogenous urea kinetics in humans.

BACKGROUND: Viscous gums enhance viscosity in the upper gastrointestinal lumen, quickly disturbing motility and promoting fluid secretion. OBJECTIVE: We sought to determine whether guar gum could acutely affect the absorption and utilization of dietary nitrogen and whether these luminal effects could also perturb the kinetics of urea. DESIGN: We studied the short-term effect of adding 1% of highly viscous guar gum to a (15)N-labeled protein meal (30 g soy protein isolate in 500 mL water) during the postprandial phase in humans. The effects on bioavailability were studied by using the [(13)C]glycine breath test (to assess gastric emptying) and (15)N enrichment in plasma amino acids (for systemic amino acid bioavailability). The kinetics of dietary and endogenous urea were assessed in plasma and urine. RESULTS: Guar gum modulated the gastric emptying kinetics of the liquid phase of the meal slightly (P < 0.05), but had no significant effect on either the systemic appearance of dietary amino acids or plasma and urinary dietary urea kinetics. Without significantly affecting plasma urea concentrations, guar gum reduced by approximately 40% the urinary excretion of endogenous urea for the first 2-h period after the meal (P < 0.01), although endogenous urinary excretion was similar at later stages. CONCLUSIONS: Guar gum did not significantly affect the bioavailability or utilization of dietary protein. We showed an early effect of guar gum on endogenous urea kinetics, which most probably arose from very early, short-term stimulation of the intestinal disposal of endogenous urea, at the expense of its urinary excretion.

Postprandial modulation of dietary and whole-body nitrogen utilization by carbohydrates in humans.

BACKGROUND: Sucrose exerts a sparing effect on whole-body protein metabolism, mainly during the absorptive phase. OBJECTIVE: We aimed to characterize the acute postprandial effect of addition of sucrose on deamination of dietary and endogenous nitrogen, with particular consideration being given to the effects of bioavailability. DESIGN: Twenty-one subjects equipped with ileal tubes ingested (15)N-labeled soy protein combined with [(13)C]glycine, with (n = 10) or without (n = 11) sucrose. Dietary and endogenous ileal flow of nitrogen were determined from the ileal effluents. The kinetics of dietary amino acid transfer to the blood were characterized by (13)CO(2) enrichment in breath and (15)N enrichment in plasma amino acids. Deamination of dietary and endogenous amino acid was determined from body urea, urinary nitrogen, and (15)N enrichment. RESULTS: (13)CO(2) recovery in breath and (15)N plasma amino acid enrichments were highly correlated (R:(2) >/= 0.95, P: < 0.001, for both meals) and markedly delayed by sucrose (half-(13)CO(2) recovery: 274 min compared with 167 min), whereas exogenous and endogenous ileal nitrogen kinetics and balances remained unchanged. Addition of sucrose halved the early (0-2 h) deamination peak of dietary nitrogen and reduced endogenous nitrogen oxidation over the first 4 h. Both were reduced by 18-24% over the 8-h period after the meal. CONCLUSIONS: Without changing the nitrogen absorptive balance, sucrose markedly affected the bioavailability profile, which is governed by gastric emptying. Endogenous and dietary nitrogen were not spared in the same way and over the same periods, showing that the metabolism of endogenous and dietary nitrogen may be affected differently by nutritional modulation, even if the effects are of a similar magnitude over the entire postprandial period.

Familial papillary carcinoma of the thyroid: a report of nine first-degree relatives of four families.

The authors report the occurrence of papillary carcinoma of the thyroid in nine first-degree relatives of four families among a consecutive series of 97 patients with papillary carcinoma of the thyroid who were operated on from 1991 to 1998. Total thyroidectomy was performed in all cases. All patients are alive without evidence of disease after a mean follow-up period of 43 months. Since in our series familial papillary carcinoma of the thyroid was found in 9.3% of patients, we suggest an adequate screening among first-degree relatives of all patients with papillary thyroid carcinoma. Because of reported aggressive behaviour of familial papillary carcinoma of the thyroid, aggressive surgical treatment plus post-operative thyroid remnant ablation with radio-iodine should be warranted in all patients.

Oncogenic risk in a chemical plant: a methological approach and preliminary results.

One of the major problems that occupational medicine has to deal with is cancer risk assessment. Recent Italian legislation requires the evaluation of occupational exposure to carcinogens in all workplaces, but a standardized method to be used in the environmental and biological criteria is generally lacking. The objective of this report is to identify a multidisciplinary approach to the research on this topic. The study is based on a chemical plant that produces pitch. The multidisciplinary approach is based on risk- and health-damage assessments. Ethical aspects are also taken into account, and the research design incorporates an informed consent for all employees. Some preliminary results are available. From the environmental point of view, all parameters provide an airborne concentration value below threshold limit values (TLVs), but biological monitoring demonstrates an increased urinary excretion of 1-OH-pyrene in all tested subjects. In conclusion, the first objective of our study is to demonstrate the carcinogenic risk of employees, searching for an agreement between environmental analysis, biological monitoring, and health effect data. A close collaboration between different professions is necessary.

Dietary protein and cardiovascular risk.

The relations between dietary protein and cardiovascular risk were first considered through their impact on blood cholesterol. Half a century after the first reports of an hypocholesterolemic effect of plant proteins, this subject is still a mater of debate, notably because of the difficulty in distinguishing between an independent effect of proteins and that of phytochemicals present in proteins preparations. In addition, many questions still have to be answered as to how the proteins may affect cholesterol metabolism. This review also describes the recent advances in new areas of research that have recently gained attention. Dietary proteins may affect cardiovascular risk through their effect on homocysteine, glutathione and nitric oxide. Although most of the data now available are still inconclusive, incoming results on these topics may prove important to appraise the role that the amount and/or the nature of dietary proteins play in the onset of cardiovascular disease.