Severe hyperinsulinemia, decreased GLUT3 and GLUT4 expression, and increased retinol binding protein 4 in a patient with chronic graft-versus-host disease post bone marrow transplantation.

Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT, especially following cGvHD. In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of inflammation, adiponectin and RBP4, body composition analysis, and the kinetics of GLUT3 and GLUT4 in circulating monocytes were evaluated. Hyperinsulinemia, associated with partial lipodystrophy, elevated RBP4, low adiponectin levels, and decreased expression of GLUT3 and GLUT4 were detected. The defects disclosed in this particular patient possibly explain, at least in part, the mechanisms underlying insulin resistance in patients undergoing BMT. It is not clear whether insulin resistance was caused by the drugs, the process itself, or the residual damage to the muscles and/or adipose tissue.

Effective combined off-pump surgical treatment and autologous bone marrow cell transplantation: a new alternative for patients with end-stage ischemic cardiomyopathy (Prapas' procedure).

OBJECTIVE: To propose an alternative method combined off-pump treatment of end-stage ischemic cardiomyopathy consisting of revascularization of ischemic areas, external reshaping of the left ventricle (LV) in order to restore near normal geometry and autologous bone marrow-derived mononuclear cell (BM-MNC) implantation. METHODS: Forty- seven patients (mean age 58+/-8.9 years) underwent the above procedure. All patients were NYHA III-IV and four were transplantation candidates. They underwent standard laboratory evaluation, transthoracic echocardiography, dipyridamole thallium scintigraphy (DTS) and cardiac magnetic resonance imaging preoperatively and at 3rd, 6th and 12th months postoperatively. After revascularization and external LV reshaping, BM-MNCs were injected into predetermined peri-infarct areas. RESULTS: Forty-five patients survived during a follow up period of 3-37 months. Ejection fraction improved from 21.7+/-7.4% to 30.6+/-6.9%, 36.5+/-4.3% and 37.7+/-4.2% at 3rd, 6th and 12th months, respectively. Left ventricular end-diastolic diameter was reduced from 66.1+/-4.9 mm to 62.6+/-3.9 mm, 60.5+/-2.9 mm and 59.3+/-4.2 mm respectively. Previously non-viable areas on DTS were found to contain viable tissue and MRI showed hypokinesia in previously akinetic areas. NYHA class improved to I-II. No significant arrhythmias were noted during the follow-up period. One patient died due to low cardiac output and one patient died due to septic shock. CONCLUSIONS: Combined off-pump surgical treatment and autologous bone-marrow mononuclear cell transplantation for end-stage ischemic cardiomyopathy is safe and feasible and appears to improve the patients' functional status.

Resistance exercise does not affect the serum concentrations of cell adhesion molecules.

BACKGROUND: Cell adhesion molecules are proteins expressed on the surface of a variety of cells and mediate the leucocyte response to inflammation. Some of these molecules are released to the plasma as soluble forms, whose presence indicates the degree of vascular endothelial activation or dysfunction. Increased concentrations of soluble adhesion molecules are thought to hamper the immune response and mediate the atherosclerotic inflammatory process. Studies on the effect of exercise on the concentrations of soluble adhesion molecules have almost exclusively used aerobic exercise. AIM: To assess the effect of resistance exercise on the serum concentrations of five cell adhesion molecules during and immediately after 30 min of exercise in lean and obese participants. METHODS: Fourteen healthy young men (eight lean and six obese) performed 3 sets of 10 resistance exercises with 10-12 repetitions at 70-75% of one repetition maximum in a circuit training fashion. Venous blood samples were drawn at baseline and at the end of the first, second and third sets. The serum concentrations of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, E-selectin, P-selectin and L-selectin were measured in a biochip array analyser. RESULTS: No significant changes were observed in the concentrations of these cell adhesion molecules during exercise, or between lean and obese participants. CONCLUSION: Our data indicate that resistance exercise of moderate to high intensity does not affect the serum concentrations of cell adhesion molecules in healthy young lean or obese men, suggesting no considerable negative effect on immune function.

Hereditary hyperferritinemia cataract syndrome in three unrelated families of western Greek origin caused by the C39 > G mutation of L-ferritin IRE.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a well-characterized autosomal dominant disease caused by mutations in the iron responsive element (IRE) of ferritin L-chain (FTL) mRNA. Mutations in the IRE result in reduced binding of the trans-acting iron regulatory proteins (IRPs) and hence in upregulation of ferritin L-chain synthesis. The disease is characterized by increased L-ferritin in serum and tissues and early onset of bilateral cataracts. Iron metabolism is normal, and there is no tissue iron overload. At least 25 nucleotide substitutions and deletions in the L-ferritin IRE have been described in families with HHCS, originating from diverse European, Australian and North American populations. We studied the molecular pathogenesis of HHCS in three unrelated kinderships of western Greek origin, with 19 affected members. We identified a relatively rare C39G mutation located in the hexanucleotide loop of L-ferritin IRE. Computational analysis of mRNA folding of mutant FTL IRE predicted that the C39 > G mutation leads to a rearrangement of base pairing in this critical region, which is likely to modify the IRP binding affinity. All subjects with HHCS were heterozygotes for the same C39G mutation. Clinical and laboratory phenotypes were described. Moreover, there was evidence of an association between this FTL IRE stem-loop mutation and very high ferritin levels. Our findings broaden the list of populations where HHCS has been described.

Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia.

Calprotectin, also known as the S100A8/A9 or MRP8/14 complex, is a major calcium-binding protein in the cytosol of neutrophils, monocytes, and keratinocytes. It differs from other S100 proteins in its zinc-binding capacity. The authors describe a 4-year-old girl with severe anemia, neutropenia, inflammation, and severe growth failure. Bone marrow examination showed moderate dyserythropoiesis. No hemolysis, iron deficiency, hemoglobinopathies, immunologic diseases, or autoantibodies were detected. Serum levels of copper and ceruloplasmin were within the normal range, although the serum zinc concentration was markedly increased (310 microg/dL). Urinary zinc excretion and erythrocyte zinc concentrations were within the normal range. Family studies showed normal zinc and copper plasma levels. The patient's plasma calprotectin concentration showed a 6,000-fold increase (2,900 mg/L) compared with normal values. The calprotectin concentration is known to be elevated in many inflammatory conditions but is generally below 10 mg/L and thus far below the levels reported in this patient. The authors describe this case as an inborn error of zinc metabolism caused by dysregulation of calprotectin metabolism, which mainly presented with the features of microcytic anemia and inflammation.