Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration.

Background & Aims: Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail.

Wolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency.

Lysosomal acid lipase deficiency is a rare, autosomal recessive condition caused by mutations in the gene encoding lysosomal acid lipase (LIPA) that result in reduced or absent activity of this essential enzyme. The severity of the resulting disease depends on the nature of the underlying mutation and magnitude of its effect on enzymatic function. Wolman's disease is a severe disorder that presents during infancy, resulting in failure to thrive, hepatomegaly, and hepatic failure, and an average life expectancy of less than 4 months.

Manganese Provision in Parenteral Nutrition: An Update.

Manganese (Mn) is an essential micronutrient required for the activity of metalloenzymes. It is an essential component of parenteral nutrition (PN), but requirements are low. Mn status is difficult to assess, with the commonest method being measurement of its concentration in whole blood.

Review of Copper Provision in the Parenteral Nutrition of Adults.

The essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis.

Review of Copper Provision in the Parenteral Nutrition of Adults [Formula: see text].

The essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis.

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors.

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation.

Manganese toxicity in critical care: Case report, literature review and recommendations for practice.

We present the case of a 62-year-old man on the intensive care unit with pancreatitis. Since early in his admission, and for the remainder of his prolonged stay in intensive care, he has received parenteral nutrition for intestinal failure. The whole blood manganese concentration was significantly increased after 2½ months of parenteral nutrition (PN).

Changes in metabolic indices in response to whole blood donation in male subjects with normal glucose tolerance.

Objectives: Previous studies have investigated the impact of venesection upon different metabolic indices in patients with various conditions (e.g., type 2 diabetes and iron overload).

Zinc: physiology, deficiency, and parenteral nutrition.

The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing.

Assessment of Becton Dickinson Plain and Serum Separator Tubes in Measurement of 25-Hydroxyvitamin D3 (25OHD3) by HPLC and Immunoassay Methods.

Background: The accuracy of 25-hydroxyvitamin D3 (25OHD3) measurement on specimens collected into serum separator tubes (SSTs) has been questioned because of possible interference by the gel. Possible interference was investigated in SSTs from Becton Dickinson (BD).

Design And Methods: Blood specimens were collected simultaneously from 50 normal subjects into plain tubes and SSTs.

Insulin-like growth factor-II: its role in metabolic and endocrine disease.

Insulin-like growth factor-II (IGF-II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF-I. IGF-II regulates foetal development and differentiation, but its role in adults is less well understood.

IGF2 and cancer.

Insulin-like growth factor 2 (IGF2) is a 7.5  kDa mitogenic peptide hormone expressed by liver and many other tissues. It is three times more abundant in serum than IGF1, but our understanding of its physiological and pathological roles has lagged behind that of IGF1.

Delta insulin-like growth factor binding protein-1 (ΔIGFBP-1): a marker of hepatic insulin resistance?

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is a hepatically synthesised protein which can be used as a marker of insulin resistance. We hypothesised that the fall in serum IGFBP-1 at 2 h following a glucose load (ΔIGFBP-10-2h) would be a more robust measure of hepatic insulin resistance than a fasting level alone.

Methods: All subjects had a standard 75 g oral GTT including IGFBP-1 and insulin measurement to enable calculation of ΔIGFBP-10-2h, ΔInsulin0-2h, and insulin sensitivity indices.

Insulin-like growth factor-I (IGF-I) and clinical nutrition.

IGF-I (insulin-like growth factor-I) is a peptide hormone, produced predominantly by the liver in response to pituitary GH (growth hormone), which is involved in a wide variety of physiological processes. It acts in an endocrine, paracrine and autocrine manner to promote growth. The production of IGF-I signals the availability of nutrients needed for its anabolic actions.

Reference change values for insulin and insulin-like growth factor binding protein-1 (IGFBP-1) in individuals with varying degrees of glucose tolerance.

Background: The reference change value (RCV) is an important parameter of biological variation used to assess the significance of differences between consecutive results obtained in a single individual. This study evaluated the RCV for insulin-like growth factor binding protein-1 (IGFBP-1) and fasting serum insulin (FSI) in individuals with different degrees of glucose tolerance.

Methods: IGFBP-1 and FSI concentrations were measured in 33 fasting subjects who had two blood samples taken 10 days apart.

The insulin-like growth factor system and nutritional assessment.

Over recent years there has been considerable interest in the role of the insulin-like growth factor (IGF) system in health and disease. It has long been known to be dysregulated in states of under- and overnutrition, serum IGF-I levels falling in malnourished patients and responding promptly to nutritional support. More recently, other proteins in this system have been observed to be dysregulated in both malnutrition and obesity.

Selection of the appropriate method for the assessment of insulin resistance.

Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations.

The relationship between glycosylated haemoglobin (HbA1c) and measures of insulin resistance across a range of glucose tolerance.

Aim: This study aimed to assess the correlation between HbA1c and insulin resistance as measured by a variety of different indices in subjects from across the glycaemic spectrum.

Methods: Subjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were studied. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test at a second visit.

Clinical diagnostics for homocysteine: a rogue amino acid?

Homocysteine has gathered considerable interest in recent years after being implicated in the pathogenesis of various clinical conditions. It has been an elusive target with many conflicting studies casting some confusion over its significance, and much more needs to be done to ascertain its pathophysiological role--especially with respect to regimes aimed at lowering its plasma concentration. Central to this is the development of robust analytical strategies for its determination.

Insulin sensitivity (Si) assessment in lean and overweight subjects using two different protocols and updated software.

Background: The standard frequently-sampled intravenous glucose tolerance test (FSIVGTT) is an alternative procedure to the clamp technique for estimating the insulin sensitivity (Si) parameter. The goal of this study was to compare Si in lean and overweight individuals in addition to assessing intra-individual reproducibility using two different protocols and updated software.

Methods: FSIVGTT was carried out in 14 lean (BMI 25 kg/m(2)) subjects using two different protocols; full (29 samples) and short (12 samples).

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study.

Heat shock protein 27 (Hsp27) is over-expressed when cells are exposed to stressful conditions that include oxidative stress. Oxidative stress has been implicated in the pathogenesis of cardiovascular disease (CVD), diabetes and insulin resistance. We have investigated the concentrations of serum Hsp27 antigen and antibodies in subjects from different glycaemic categories, who either did or did not have established CVD.

Serum insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation status in subjects with and without ischaemic heart disease.

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the activity of IGF-I. It exists in serum as phosphorylated and less phosphorylated forms. We wished to measure serum levels of both these forms of IGFBP-1, using a novel assay, in subjects with, or without ischaemic heart disease (IHD).

Biological variation in fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) among individuals with a varying glucose tolerance.

Objective: To evaluate the biological variation of serum insulin-like growth factor binding protein-1 (IGFBP-1) in individuals with different degrees of glucose tolerance.

Research Design And Methods: IGFBP-1 was measured in 42 fasted subjects with: normal glucose tolerance (NGT=15), impaired fasting glucose (IFG=9), impaired glucose tolerance (IGT=9) and type 2 diabetics (DM=9). Short- and long-term reproducibility was determined for IGFBP-1.