Peripheral nerve regeneration and neurotrophic factors

The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies.     

Respiratory Rate as a Determinant of Optimal Pacing Rate

Des essais ont été faits dans ľutilisation des paramètres bialogiques pour déterminer la fréquence optimale de stimulation cardiaque. Dans cette étude, le rapport entre fréquence respiratoire et fréquence cordiaque a étéétabli chez 67 patients au cours de ľexercice. Ensuite, un système de stimulation cardiaque qui repondrait àľactivation radiotélémétrique a été posé chez onze patients. Dans deux cos un système automatique a été implanté avec succès. A present, les résultats de cette stimulation pilotée par la fréquence respiratoire sont satisfaisants.
Efforts have been made to utilize biologic parameters for determining optimal cardiac pacing rates. In this study of 67 patients, a significant relationship between heart rate and respiratory rate was observed during dynamic exercise. A system using a radiofrequency activator to modify pacing rate is described. Eleven patients have received VVI pacemakers with a similar implanted radioreceiver coil. In two patients the fully automatic system has been successfully implanted. The experience with respiratory rate as a determinant of pacing rate is encouraging.     

Increasing Cardiac Rate by Tracking the Respiratory Rate

Un stimulateur asservi qui utilise la fréquence venlilatoire comme capteur a été implunté chez 22 patients, dont 19 pour la stimulation ventriculaire et 3 pour la stimulation auriculaire. Le niveau d'exercice atteint en utilisant ce système a été toiijours supérieur à celui de la stimulation ventriculaire à fréquence fixe. En plus, aucun capteur chimique ou mécanique n'était utilisé; le capteur même est simple, durable et utilise une faible énérgie. Done, ce système s'adapte facilement à chaque patient individuel.     

Prevention of Sudden Cardiac Death After a First Myocardial Infarction by Pharmacologic or Surgical Antiadrenergic Interventions

Antiadrenergic Interventions and Prevention of Sudden Death after MI. Introduction: Growing evidence points to sympathetic hyperactivity as one critical trigger for life-threatening arrhythmias among postmyocardial infarction patients. Methods and Results: We have evaluated, in a placebo-controlled multicenter study, the efficacy of a β-adrenergic blocking agent (oxprenolol 160 mg) and of a selective left cardiac sympathetic denervation in preventing sudden death in patients with a first and anterior myocardial infarction. Two patient groups were studied. The high-risk group included 144 patients who survived a myocardial infarction complicated by either ventricular tachycardia or fibrillation. The relatively low-risk group included 869 patients whose myocardial infarction did not have these complications; they were allocated only to placebo or oxprenolol. Randomization took place 30 days postmyocardial infarction; mean follow-up was 22 months. In the high-risk group the sudden cardiac death (crude rate) in the placebo subgroup was indeed high (21.3%), and was strikingly reduced to 2.7% and to 3.6% by oxprenolol and by left cardiac sympathetic denervation, respectively (P < 0.05). In the low-risk group the sudden cardiac death (crude rate) in the placebo subgroup was 5.2% and was still reduced by oxprenolol to 1.6% (P < 0.05). The results for total mortality were quite similar to those for sudden death iu both groups. Conclusion: This study, unique for the populations studied and for one of the treatments used, demonstrates that pharmacologic and surgical antiadrenergic interventions significantly reduce sudden cardiac death in postmyocardial infarction patients at high and at low risk. With due consideration to the relatively small size of the high-risk group, it seems reasonable to suggest that left cardiac sympathetic denervation may be considered as a possible alternative for high-risk patients with contraindications to beta blockers. (J Cardiovasc Electrophysiol, Vol 3, pp. 2–16, February 1992)     

The white blood cell count: its relationship to plasma insulin and other cardiovascular risk factors in healthy male individuals

Targher G, Seidell JC, Tonoli M, Muggeo M, De Sandre G, Cigolini M (Division of Endocrinology and Metabolic Diseases, Institute of Clinical Medicine, University of Verona, Italy; and Department of Chronic Diseases and Environmental Epidemiology-RIVM, Bilthoven, The Netherlands). The white blood cell count: relationship to plasma insulin and other cardiovascular risk factors in healthy males. J Intern Med 1996; 239: 435–41. Objectives. To evaluate the relationships of total and differential white blood cell (WBC) count to the components of the so-called insulin resistance syndrome. Subjects and design. The study population consisted of a random sample of 90 38-year-old healthy men with normal glucose tolerance. Interventions. A 75 g oral glucose tolerance test was performed in all participants. Main outcome measures. Total and differential WBC count, lipids, blood pressure, plasma glucose, C-peptide and insulin (at fasting and 2 h after glucose load). Results. Total WBC count correlated consistently with plasma 2-h glucose (r=0.38; P<0.001), fasting and 2-h postload insulin (r=0.26 and r=0.33; P<0.01–0.001, respectively) and C-peptide (r=0.28 and r=0.32; P<0.01–0.001) concentrations. Smokers had significantly higher total leukocytes (P<0.01), neutrophils and lymphocytes than nonsmokers. Furthermore, total WBC count correlated positively with body mass index, blood pressure, plasma triglycerides, fibrinogen, and negatively with HDL cholesterol concentration. As differential WBC count, most variables correlated essentially to neutrophils and/or lymphocytes, whereas plasma insulin and C-peptide concentrations correlated essentially to lymphocytes and monocytes, but not to neutrophils. In a multiple linear regression analysis, only 2-h plasma glucose (P<0.01) and fibrinogen (P<0.05) were positive predictors of total WBC count after adjusting for all potentially confounding variables. Conclusions. The results indicate that increased, albeit normal, WBC count associates with the cluster of metabolic and haemodynamic disorders typical of the insulin resistance syndrome, and suggest that increased WBC count may be yet another component of this syndrome.     

Design of hydropathically complementary peptides for Big Endothelin affinity purification

Molecular recognition between Big Endothelin (Big ET) and a computer generated peptide hydropathically complementary to Big ET[16-29] sequence has been studied by analytical high performance liquid affinity chromatography (HPLAC), circular dichroism (CD) and nuclear magnetic resonance (NMR) experiments. Specific binding was observed between solid support immobilized complementary peptide and Big ET[1-38], [1-32], and [16-32], but not with Big ET fragments [1-21], [16-21], [22-32], and [22-38], obtained by chymotrypsin proteolytic degradation. Selectivity in the recognition process was clearly demonstrated by the ability of complementary peptide affinity column to purify the Big ET molecule from complex peptide mixtures, even when present in very low concentrations. Similar selectivity was evidenced with the Big ET fragment [16-32], [NH₂-HLDIIWVNTPEHIVPYG-COOH] containing the entire hydropathically complementary sequence. Binding was followed by marked spectroscopic changes, as monitored by circular dichroism and one- and two-dimensional nuclear magnetic resonance experiments. The NMR spectra of the complementary peptides 1:1 mixture showed variations in the chemical shifts of proton resonances in several residues, both in the main chain (amide protons) and in the side chains (aliphatic and aromatic protons). These data support the hypothesis of a multilocalized type of interaction between complementary peptides, where many residues along the peptide chains participate in co-operative stabilizing contacts in the forming complex.     

Microenvironment and stem properties of bone marrow-derived mesenchymal cells

Adult stem cells are self-renewing, pluripotent, and able to repopulate the tissue in which they reside. Cells endowed with these properties have been isolated from several tissues and an increasing number of reports provide evidence of their ability, following transplantation, to engraft host tissues other than those of their origin. In this setting, interest in the well-documented capacity of bone marrow stromal cells to undergo multilineage differentiation is growing. Neural and cardiomyogenic lineages have recently been proposed as additional differentiative pathways of these cells. However, culture conditions and inductive molecules can alter the behavior of bone marrow stromal cells and the microenvironment is critical for proper in vivo delivery. The maintenance of their stem properties and the possibility of reprogramming their commitment is a field of primary interest given the potential use of these cells in regenerative medicine. We discuss here how the microenvironmental cues, and the growth factors that physiologically govern commitment and subsequent differentiation, influence the properties of bone marrow stromal cells and modulate their engraftment into host tissues.