Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction

Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were pre-prepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the perii-nfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.     

Dendroaspis natriuretic peptide in hepatic cirrhosis

OBJECTIVES: Dendroaspis natriuretic peptide (DNP) is a novel peptide that is structurally similar to atrial, brain, and C-type natriuretic peptides. Many natriuretic peptides are increased in hepatic cirrhosis, but the role of DNP in cirrhosis is unknown at present. The aim of the study was to investigate plasma levels of dendroaspis natriuretic-like immunoreactivity in cirrhosis. METHODS: We measured plasma concentrations of DNP by radioimmunoassay methods in 12 cirrhotic patients without ascites and 44 cirrhotic patients with ascites, and compared these values with 20 age-matched healthy subjects. Renal function, plasma cGMP concentration, plasma renin activity, and plasma endothelin concentration were measured in each patient. RESULTS: Patients without ascites had circulating levels of DNP similar to those of healthy subjects. By contrast, patients with ascites had increased circulating DNP levels compared to both patients without ascites and healthy subjects. In addition, circulating levels of DNP increased in relation to the severity of cirrhosis. Significant positive correlations were also found between DNP levels, endothelin concentrations, and plasma renin activity. CONCLUSIONS: The results of this study indicate that plasma DNP is increased in cirrhotic patients with ascites.     

Levels of plasma total adrenomedullin are related with two acute phase inflammatory reactants (fibrinogen and sialic acid) but not with markers of endothelial dysfunction in Type 1 diabetes Adrenomedullin and vascular risk factors in Type 1 DM

Adrenomedullin (AM), an ubiquitous regulatory peptide with different actions, is known to be elevated in different clinical situations, including diabetes mellitus (DM), but its potential role in the pathogenesis of diabetic vascular complications is not clear. In the present study, we examined plasma total AM levels, and their association with different markers of endothelial dysfunction and with other established risk factors for cardiovascular diseases, in patients with Type 1 DM. We studied a total of 155 patients, 117 patients without any kind of vascular complications, 24 patients with retinopathy only, and 14 patients with retinopathy and microalbuminuria but normal renal function. None of them had clinical evidence of atherosclerotic disease. Compared with the control group (64 healthy participants), patients had raised fibrinogen, soluble E-selectin ((s)E-selectin), vascular cellular adhesion molecule (VCAM), angiotensin converting enzyme (ACE), and von Willebrand factor (vWf) (P<.001 in all cases), but plasma total AM, endothelin (ET), sialic acid, and homocysteine were not raised. In the diabetic group, AM levels correlated significantly with sialic acid (r=.16; P<.05), but a more significant correlation was found with fibrinogen (r=.30; P<.001). No correlation was found with the other parameters studied. In summary, plasma total AM levels seem to correlate with inflammatory markers but not with endothelial dysfunction markers in Type 1 diabetic patients without atherosclerotic disease.     

Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy.

OBJECTIVES: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI). BACKGROUND: Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood. METHODS: We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone. RESULTS: Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05). CONCLUSIONS: With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.     

Face Naming and Retrieval Inhibition in Old and Very Old Age

Background/Study Context: Aging has traditionally been related to impairments in proper name retrieval. This study analyzed the possible role of the Inhibitory Deficit Hypothesis in explaining face naming impairments during aging. The dynamics of inhibition have been thoroughly studied by the retrieval-practice paradigm (Anderson, Bjork, & Bjork, 1994, Journal of Experimental Psychology: Learning, Memory, and Cognition, 20, 1063–1087) and its aftereffect, the retrieval-induced forgetting effect.

Methods: A version of the retrieval-practice paradigm was employed: younger-old (YO; mean age = 66.40, SD = 3.94) and older-old (OO; mean age = 80.94, SD = 4.53) adults were asked to repeatedly name faces of categorically related famous people.

Results: Retrieval-induced forgetting for names was observed in the YO group but not in the OO group.

Conclusion: These findings indicate that whereas the YO adults had enough resources to inhibit intrusive names, OO adults were not able to suppress competing names, supporting the proposal of the Inhibitory Deficit Hypothesis at older ages.     

Phenomenology of "Lubag" or X-linked dystonia-parkinsonism.

X-linked dystonia-parkinsonism (XDP), or Lubag syndrome, is known to cause progressive dystonia, with or without parkinsonism, among Filipino male adults with maternal roots from the Philippine island of Panay. We present cinematographic material of 11 cases of Lubag carrying the XDP haplotypes who manifest with a wide spectrum of movement disorders, including dystonia, tremor, parkinsonism, myoclonus, chorea, and myorhythmia. Because of overlapping features, Lubag patients are commonly misdiagnosed as idiopathic dystonia, essential tremor, Parkinson's disease, or Parkinson's-plus syndromes. Thus, it is imperative to elicit an exhaustive family history in any Filipino male adult who presents with a movement disorder.