Insulin-like growth factor-II and bioactive proteins containing a part of the E-domain of pro-insulin-like growth factor-II

Insulin-like growth factor (IGF)-II is considered to function as an important fetal growth factor, which is structurally and functionally related to IGF-I and proinsulin. At least in vitro, IGF-II actions are mediated through the IGF-I receptor and to a lesser extent the insulin receptor. After birth, the function of IGF-II is less clear although in adults the serum level of IGF-II exceeds that of IGF-I several fold. The IGF-II gene is maternally imprinted, with exception of the liver and several parts of the brain, where it is expressed from both alleles. The regulation, organization, and translation of the IGF-II gene is complex, with five different putative promotors leading to a range of noncoding and coding mRNAs. The 180-amino acid pre-pro-IGF-II translation product can be divided into five domains and include a N-terminal signal peptide of 24 amino acid residues, the 67 amino acid long mature protein, and an 89 residues extension at the COOH terminus, designated as the E-domain. After removal of the signal peptide, the processing of pro-IGF-II into mature IGF-II requires various steps including glycosylation of the E-domain followed by the action of endo-proteases. Several of these processing intermediates can be found in the human circulation. There is increasing evidence that, besides IGF-II, several incompletely processed precursor forms of the protein, and even a 34-amino acid peptide (preptin) derived from the E-domain of pro-IGF-II, exhibit distinct biological activities. This review will focus on the current insights regarding the specific roles of the latter proteins in cancer, glucose homeostasis, and bone physiology. To address this topic clearly in the right context, a concise overview of the biological and biochemical properties of IGF-II and several relevant aspects of the IGF system will be provided

Effects of Seven Fungicides on Non-Target Aquatic Fungi

Aquatic risk assessments for fungicides are carried out without information on their toxicity to non-target aquatic fungi. This might cause an underestimation of the toxic effects to the aquatic fungal community. This study focuses on the question whether recently derived concentrations limits for fungicides considered to protect populations of primary producers and (in)vertebrates also do protect the aquatic fungi. A panel of fungal species and Oomycetes was isolated and identified from unpolluted surface waters in the Netherlands. Toxicity tests were used to determine effects of seven fungicides with different modes of actions. For the triazoles epoxiconazole and tebuconazole, the chronic lowest observable effect concentration was lower than the regulatory acceptable concentration based on acute HC5 values

Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs)

Call Characteristics of Patients Suspected of Transient Ischemic Attack (TIA) or Stroke During Out-of-Hours Service: A Comparison Between Men and Women

Background: In the Netherlands, a digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC) is used. Differences in help-seeking behavior between men and women when transient ischemic attack (TIA) or stroke is suspected could potentially affect telephone triage and allocation of urgency. Aim: To assess patient and call characteristics and allocated urgencies between women and men who contacted OHS-PC with suspected TIA/stroke. Methods: A cross-sectional study of 1,266 telephone triage recordings of subjects with suspected neurological symptoms calling the OHS-PC between 2014 and 2016. The allocated urgencies were derived from the electronic medical records of the OHS-PC and the final diagnosis from the patient's own general practitioner, including diagnoses based on hospital specialist letters. Results: Five hundred forty-six men (mean age = 67.3 ± 17.1) and 720 women (mean age = 69.6 ± 19.5) were included. TIA/stroke was diagnosed in 294 men (54%) (mean age = 72.3 ± 13.6) and 366 women (51%) (mean age = 78.0 ± 13.8). In both genders, FAST (face-arm-speech test) symptoms were common in TIA/stroke (men 78%, women 82%) but also in no TIA/stroke (men 63%, women 62%). Men with TIA/stroke had shorter call durations than men without TIA/stroke (7.10 vs. 8.20 min, p = 0.001), whereas in women this difference was smaller and not significant (7.41 vs. 7.56 min, p = 0.41). Both genders were allocated high urgency in 75% of the final TIA/stroke cases. Conclusion: Overall, patient and call characteristics are mostly comparable between men and women, and these only modestly assist in identifying TIA/stroke. There were no gender differences in allocated urgencies after telephone triage in patients with TIA/stroke

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children:The iAGE Study

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), β-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and β-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.</p

Making IT governance work in a Sarbanes-Oxley world /

Includes bibliographical references and index