Archive of Medical Research

Comment on \”vitamin D discovery outpaces FDA decision making\”

Boucher BJ.

Centre for Diabetes & Metabolic Medicine, Barts & the London Medical & Dental School, London, UK.

The health benefits of vitamin D greatly outweigh the health risks.

Grant WB, Garland CF.

Sunlight, Nutrition, and Health Research Center (SUNARC) P.O. Box 641603, San Francisco, CA 94164‐1603.

Modulation of Na(+)-H(+) exchange isoforms NHE1 and NHE3 by insulin-like growth factor-1 in isolated bovine articular chondrocytes.

Incubation with serum modulates the transporters that regulate intracellular pH (pH(i)) in articular chondrocytes, upregulating acid extrusion by Na(+)-H(+) exchange (NHE). There is stimulation of NHE1, together with induction of NHE3 activity. These isoforms exhibit differential responses to components of mechanical load experienced by chondrocytes during joint loading. The identity of the component(s) of serum responsible is unknown. A possibility, however, is insulin-like growth factor-1 (IGF-1), present in normal cartilage and found at enhanced levels in osteoarthritic tissue. In the present study, the effects of IGF-1 on pH(i) regulation have been characterized using fluorescence measurements of bovine articular chondrocytes, and the sensitivity of pH(i) regulation to hyperosmotic shock and raised hydrostatic pressure determined. For cells isolated in the absence of IGF-1, pH(i) recovery following acidification was predominantly mediated by NHE1. Recovery was enhanced when cells were incubated for 18 h with 20 ng mL(-1) IGF; this effect represented increased acid extrusion by NHE1, supplemented by NHE3 activity. NHE3 activity was not detected in IGF-1-treated cells that had been incubated with the protein synthesis inhibitor cycloheximide, although NHE1 activity was unaffected. In the absence of IGF-1, suspension in hyperosmotic solutions or raised hydrostatic pressure enhanced pH(i) recovery of acidified cells. This response was missing in cells incubated with IGF-1. Unresponsiveness to hyperosmotic shock represented inhibition of NHE3 activity, and was prevented using the protein kinase A inhibitor KT5720. For raised hydrostatic pressure, a decrease in NHE1 activity was responsible, and was prevented by the protein kinase C inhibitor chelerythrine. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Tattersall AL, Wilkins RJ.

Department of Physiology, Anatomy and Genetics, Sherrington Building, Parks Road, Oxford, OX1 3PT, United Kingdom.

Brain, mind and limitations of a scientific theory of human consciousness.

In biological terms, human consciousness appears as a feature associated with the functioning of the human brain. The corresponding activities of the neural network occur strictly in accord with physical laws; however, this fact does not necessarily imply that there can be a comprehensive scientific theory of consciousness, despite all the progress in neurobiology, neuropsychology and neurocomputation. Predictions of the extent to which such a theory may become possible vary widely in the scientific community. There are basic reasons-not only practical but also epistemological-why the brain-mind relation may never be fully \”decodable\” by general finite procedures. In particular self-referential features of consciousness, such as self-representations involved in strategic thought and dispositions, may not be resolvable in all their essential aspects by brain analysis. Assuming that such limitations exist, objective analysis by the methods of natural science cannot, in principle, fully encompass subjective, mental experience. BioEssays 30:499-505, 2008. (c) 2008 Wiley Periodicals, Inc.

Gierer A.

Max Planck Institute for Developmental Biology, Spemannstrasse 35, D‐72076 Tübingen, Germany.

Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro.

Dexamethasone/ascorbic acid/glycerolphosphate (DAG) and bone morphogenic protein (BMP)-2 are potent agents in cell proliferation and differentiation pathways. This study investigates the in vitro interactions between dexamethasone and BMP-2 for an osteoblastic differentiation of mesenchymal stem cells (MSCs). Bone marrow-derived human MSCs were cultured with DAG (group A), BMP-2 + DAG (group B), and DAG + BMP-2 combined with a porous collagen I/III scaffold (group C). RT-PCR, ELISA, immuncytochemical stainings and flow cytometry analysis served to evaluate the osteogenic-promoting potency of each of the above conditions in terms of cell morphology/viability, antigen presentation, and gene expression. DAG induced collagen I secretion from MSCs, which was further increased by the combination of DAG + BMP-2. In comparison, the collagen scaffold and the control samples showed no significant influence on collagen I secretion of MSCs. DAG stimulation of MSCs led also to a steady but not significant increase of BMP-2 level. A DAG and more, a DAG + BMP-2, stimulation increased the number of mesenchymal cells (CD105+/CD73+). All samples showed mRNA of ALP, osteopontin, Runx2, Twist 1 and 2, Notch-1/2, osteonectin, osteocalcin, BSP, and collagen-A1 after 28 days of in vitro culture. Culture media of all samples showed a decrease in Ca(2+) and PO(4) (2-) concentration, whereas a collagen-I-peak only occurred at day 28 in DAG- and DAG + BMP-2-stimulated bone marrow cells. In conclusion, BMP-2 enhances DAG-induced osteogenic differentiation in mesenchymal bone marrow cells. Both agents interact in various ways and can modify osteoblastic bone formation. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Jäger M, Fischer J, Dohrn W, Li X, Ayers DC, Czibere A, Prall WC, Lensing-Höhn S, Krauspe R.

Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich‐Heine University Medical School, Moorenstr. 5, D‐40225 Düsseldorf, Germany.

Cupiennius salei and Achaearanea tepidariorum: Spider models for investigating evolution and development.

The spiders Cupiennius salei and Achaearanea tepidariorum are firmly established laboratory models that have already contributed greatly to answering evolutionary developmental questions. Here we appraise why these animals are such useful models from phylogeny, natural history and embryogenesis to the tools available for their manipulation. We then review recent studies of axis formation, segmentation, appendage development and neurogenesis in these spiders and how this has contributed to understanding the evolution of these processes. Furthermore, we discuss the potential of comparisons of silk production between Cupiennius and Achaearanea to investigate the origins and diversification of this evolutionary innovation. We suggest that further comparisons between these two spiders and other chelicerates will prove useful for understanding the evolution of development in metazoans. BioEssays 30:487-498, 2008. (c) 2008 Wiley Periodicals, Inc.

McGregor AP, Hilbrant M, Pechmann M, Schwager EE, Prpic NM, Damen WG.

Institute for Genetics, Evolutionary Genetics, University of Cologne, Köln, Germany.

A Rare Coronary Anomaly: Double Right.

Angelini P.

Texas Heart Institute; Baylor College of Medicine, Houston, Texas, USA.

Jane Somerville.

Warnes CA.

Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

ST-segment Elevation in Lead Augmented Vector Right may also be Caused by Diffuse Left Main Coronary Artery Vasospasm Without Fixed Stenosis.

ST-segment deviation in lead augmented vector right (aVR) is useful for evaluating patients with acute coronary syndrome (ACS). The ST-segment elevation in this aVR in the patient with clinically suspected acute coronary syndrome suggests a strong possibility of left main coronary artery (LMCA) obstruction due to fixed stenosis. In this article, we report the first case, to our knowledge, of ST-segment elevation in lead aVR due to diffuse LMCA spasm. Copyright (c) 2008 Wiley Periodicals, Inc.

Duygu H, Yavuzgil O, Erturk U, Zoghi M, Ozerkan F.

Department of Cardiology, Ege University, Izmir, Turkey.

Diagnostic Approach and Treatment Strategy in Tachycardia-induced Cardiomyopathy.

BACKGROUND: Due to the absence of differential guidelines for heart failure with tachyarrhythmia, it is difficult to diagnose tachycardia-induced cardiomyopathy (TIC) at the initial visit. Furthermore, clinical outcomes of rate versus rhythm control in TIC are unclear. HYPOTHESIS: Because the etiology of TIC is different from dynamic cardiomyoplasty (DCMP), differential parameters may be present. METHODS: We assessed 21 patients with TIC (15 men; mean age, 50 +/- 14 years) and 21 control patients with idiopathic DCMP. We assessed clinical courses, echocardiographic parameters, as well as outcomes by treatment. RESULTS: In the TIC group, the related tachyarrhythmias were atrial fibrillation (n = 12), atrial flutter (n = 5), atrial tachycardia (n = 3) and paroxysmal supraventricular tachycardia (n = 1). After treatment, all patients became asymptomatic and the ejection fraction (EF) improvement (DeltaEF >/=15%) was observed in all patients (left ventricular ejection fraction [LVEF], 30 +/- 11%(initial) versus 58 +/- 6%(last)). In the idiopathic DCMP group, no patient showed EF improvement (EF increase </= 5%), and 4 patients (19%) underwent heart transplantation. Left ventricle (LV) mass indices, volumes adjusted by BSA, and dimensions were smaller in the TIC group than in the idiopathic DCMP group. Of those, LV end-diastolic dimension was the only independent predictor of TIC in multiple regression analysis (odds ratio [OR] 0.742 per 1 mm, 95% confidence ratio [CI] 0.618 to 0.891, p = 0.001). The Association of University Cardiologists (AUC) was 0.908 on receiver-operating characteristic (ROC) curve analysis and LV end-diastolic dimension </= 61% mm could predict TIC with a sensitivity of 100% and a specificity of 71.4%. After restoration of sinus rhythm (n = 8), one experienced recurrent TIC after discontinuation of amiodarone. After control of heart rate (n = 13), one experienced recurrent TIC due to poor control of heart rate (log-rank test, p = 0.808). There were no differences in the echocardiographic parameters between the 2 groups before and after treatment except for the larger initial LV volumes in the rhythm control. CONCLUSIONS: In patients presented as heart failure with tachyarrhythmia, initial echocardiographic parameters, especially LV end-diastolic dimension, help to differentiate TIC from idiopathic DCMP. Rate control was as effective as rhythm control for EF improvement and prognosis. Copyright (c) 2008 Wiley Periodicals, Inc.

Jeong YH, Choi KJ, Song JM, Hwang ES, Park KM, Nam GB, Kim JJ, Kim YH.

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.