Elevated Whole-Blood Manganese Levels in Adult Patients Prescribed "Manganese-Free" Home Parenteral Nutrition.

BACKGROUND: Manganese toxicity can occur as a complication of home parenteral nutrition (HPN). Patients can present with Parkinson disease-like symptoms. Preparations of trace elements (TEs) in parenteral nutrition (PN) generally provide amounts in excess of requirements. Our previous review observed 60% of adult HPN patients had high whole-blood manganese levels. Multi-TE (MTE) solutions were subsequently removed from all HPN formulations in January 2015. The aim of this evaluation was to determine whole-blood concentrations of manganese in adult patients receiving HPN to establish whether levels are now maintained within the normal reference range. METHODS: A retrospective review of whole-blood manganese levels in all patients receiving HPN between January 2018 and January 2019 from 1 hospital site was carried out. RESULTS: 100 patients were included in the review (59 female and 41 male). Normal whole-blood manganese levels (73-219 nmol/L) were observed in 70% of patients and elevated levels (>219 nmol/L) in 30% of patients. In the patients with elevated levels, 57% had not received manganese supplementation for at least 1 year prior to manganese being measured. Markers of cholestasis were similar between the 2 groups. CONCLUSIONS: Incidence of elevated whole-blood manganese concentrations in patients receiving HPN decreased from 60% to 30% upon discontinued use of an MTE solution. Elevated levels remain a concern despite patients being prescribed "manganese-free" PN. Patients receive this TE in amounts adequate to meet requirements through contamination and dietary intake alone, suggesting additional parenteral supplementation of manganese is not required.

The relationship between plasma albumin, alkaline phosphatase and pyridoxal phosphate concentrations in plasma and red cells: Implications for assessing vitamin B6 status.

BACKGROUND: Plasma concentrations of most vitamins decrease as part of the systemic inflammatory response (SIR). Thus low plasma values do not necessarily indicate deficiency. Vitamin B6 status is usually assessed by measurement of pyridoxal phosphate (PLP) in plasma, although vitamin concentrations in blood cells tend to be better markers of cellular stores. In health, plasma PLP appears to be determined primarily by intake, its binding to albumin, and its hydrolysis by alkaline phosphatase (ALP). OBJECTIVE: To examine, using in vitro studies, the effect of albumin concentration and ALP activity on PLP concentration in plasma and red blood cells of healthy subjects (HS) and critically ill patients (CI). DESIGN: Heparin and EDTA (ALP inhibited) whole blood samples from HS (n = 8) and CI (n = 26) were incubated with PLP. Concentration of PLP in plasma and red cells was measured. Albumin and ALP levels were determined in plasma. RESULTS: In PLP incubated heparin samples, there was a strong direct relationship between albumin in the concentration range 10-44 g/L and increase in plasma PLP concentration (rs = 0.93, P < 0.001) and an inverse relationship with increase in red cell PLP concentration (rs = -0.90, P < 0.001). In contrast, ALP activity was inversely associated with increase in plasma PLP concentration (rs = -0.42; P = 0.013) and directly associated with red cell PLP concentration (rs = 0.49; P = 0.003). CONCLUSIONS: Plasma albumin concentration and to a lesser extent ALP activity influences PLP concentration in plasma and red cells. In conditions associated with low albumin (e.g. SIR) or altered ALP activity, red cell PLP measurements are more likely to be reliable than plasma measurements in differentiating true from apparent vitamin B6 deficiency and to guide vitamin B6 supplementation.

The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty.

BACKGROUND: Studies indicate that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, other lipid-soluble vitamins decrease during the systemic inflammatory response, and this response may confound the interpretation of plasma 25(OH)D. OBJECTIVE: The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response. DESIGN: Patients (n = 33) who underwent primary knee arthroplasty had venous blood samples collected preoperatively and postoperatively (beginning 6-12 h after surgery and on each morning for 5 d) for the measurement of 25(OH) D, vitamin D-binding protein, parathyroid hormone (PTH), calcium, C-reactive protein, and albumin. A final sample was collected at 3 mo. RESULTS: Preoperatively, most patients were 25(OH)D deficient (<50 nmol/L) and had secondary hyperparathyroidism (PTH > 5 pmol/L). Age, sex, body mass index, season, medical history, and medication use were not associated with significant differences in preoperative plasma 25(OH)D concentrations. By day 2 there was a large increase in C-reactive protein concentrations (P < 0.001) and a significant decrease in 25(OH)D of ≈40% (P < 0.001). C-reactive protein, 25(OH)D, and calculated free 25(OH)D had not returned to preoperative concentrations by 5 d postoperatively (all P < 0.001). At 3 mo, 25(OH)D and free 25(OH)D remained significantly lower (20% and 30%, respectively; P < 0.01). CONCLUSION: Plasma concentrations of 25(OH)D decrease after an inflammatory insult and therefore are unlikely to be a reliable measure of 25(OH)D status in subjects with evidence of a significant systemic inflammatory response.

The skeletal muscle-specific glycogen-targeted protein phosphatase 1 plays a major role in the regulation of glycogen metabolism by adrenaline in vivo.

Adrenaline and insulin are the major hormones regulating glycogen metabolism in skeletal muscle. We have investigated the effects of these hormones on the rate-limiting enzymes of glycogen degradation and synthesis (phosphorylase and glycogen synthase respectively) in GM-/- mice homozygous for a null allele of the major skeletal muscle glycogen targeting subunit (GM) of protein phosphatase 1 (PP1). Hyperphosphorylation of Ser14 in phosphorylase, and Ser7, Ser640 and Ser640/644 of GS, in the skeletal muscle of GM-/- mice compared with GM+/+ mice indicates that the PP1-GM complex is the major phosphatase that dephosphorylates these sites in vivo. Adrenaline caused a 2.4-fold increase in the phosphorylase (-/+AMP) activity ratio in the skeletal muscle of control mice compared to a 1.4 fold increase in GM-/- mice. Adrenaline also elicited a 67% decrease in the GS (-/+G6P) activity ratio in control mice but only a small decrease in the skeletal muscle of GM-/- mice indicating that GM is required for the full response of phosphorylase and GS to adrenaline. PP1-GM activity and the amount of PP1 bound to GM decreased 40% and 45% respectively, in response to adrenaline in control mice. The data support a model in which adrenaline stimulates phosphorylation of phosphorylase Ser14 and GS Ser7 in GM+/+ mice by both kinase activation and PP1-GM inhibition and the phosphorylation of GS Ser640 and Ser640/644 by PP1-GM inhibition alone. Insulin decreased the phosphorylation of GS Ser640 and Ser640/644 and stimulated the GS (-/+G6P) activity ratio by approximately 2-fold in the skeletal muscle of either GM-/- and or control mice, but the low basal and insulin stimulated GS activity ratios in GM-/- mice indicate that PP1-GM is essential for maintaining normal basal and maximum insulin stimulated GS activity ratios in vivo.