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.     

How Important Are Brain Banks for Alcohol Research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.     

Corticotropin-releasing factor: a marked circadian rhythm in primate cerebrospinal fluid peaks in the evening and is inversely related to the cortisol circadian rhythm

Continuous sampling of cerebrospinal fluid (CSF) over 24-h periods in 10 rhesus monkeys revealed a 2-fold, highly reproducible circadian rhythm in CRF concentrations. Peak CRF values of 77.9 +/- 6.4 pg/ml occurred in the evening at 1930 h, while the CRF nadir (38.4 +/- 4.2 pg/ml) occurred at 0745 h. Simultaneously sampled CSF cortisol peaked at 0913 h, with a nadir at 2226 h. Both CRF and cortisol rhythms closely fit sinusoidal circadian models, with r2 values of 0.94 and 0.92, respectively. While hypothalamic CRF is regarded as a major physiological regulator of pituitary ACTH secretion and, thereby, of the circadian and stress-related release of cortisol from the adrenal gland, CRF and CRF receptors are also widely distributed in other brain areas of primates and rodents. The marked difference in the circadian rhythm of CRF vs. that of cortisol suggests that CRF in CSF reflects or mediates some nonhypophysiotropic brain functions of this peptide.     

Incontinence,Voiding Dysfunction,and Other Urologic Complications After Radiotherapy for Gynecologic Malignancies

Women with newly diagnosed gynecologic cancer will undergo treatment with surgery, radiation, or combination therapy. A considerable proportion of these women will develop urologic complications including urinary incontinence, urinary retention, radiation cystitis, ureteral stricture, or genitourinary fistula. Diagnosis is typically made with a careful history, physical exam, endoscopy, urodynamics, and imaging. Non-surgical and surgical management of urologic complications following radiotherapy is complicated by local tissue damage resulting in inferior success rates when compared to the general population. It is imperative that the patient and physician understand the complexity of treatment and manage expectations accordingly.     

Microinjection of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus stimulates gastric contractility

Changes in gastric contractility following microinjection of thyrotropin-releasing hormone (TRH) into the paraventricular nucleus of the hypothalamus (PVN) were examined in fasted, urethane-anesthetized rats. Gastric contractility was measured with extraluminal force transducers and analysed by computer. Unilateral and bilateral PVN microinjections of TRH (0.5 and 1.0 μg) significantly increased the force index of gastric contractions from 0 to 60 min postinjection, when compared with animals microinjected with 0.1 μg TRH, 0.1% BSA or TRH (0.5 and 1.0 μg TRH) in sites adjacent to the PVN. The gastric force index was also significantly elevated from 61 to 120 min postinjection in rats receiving bilateral PVN microinjections of TRH (0.5 and 1.0 μg). Peak gastric responses occurred within 10–20 min postinjection and represented an approximately eight-fold increase over basal values. In the remaining groups, the force index was not significantly altered from preinjection values. The excitatory action of TRH (1.0 μg) on gastric contractility was completely abolished by subdiaphragmatic vagotomy. These results suggest that TRH acts within the PVN to stimulate gastric contractility via vagal-dependent pathways.     

The functional treatment of a third proximal phalanx fracture

Aggressive, cool soaks, and buddy taping with thoughtful frequent followups allowed this patient to return to competition safely with full function in a remarkably short period of time. Similar treatment to some soft tissue injuries of the hand and other stable fractures have been done with equal success.     

Monoamine oxidase type a: differences in selectivity towards l-norepinephrine compared to serotonin

l-Norepinephirine and serotonin have been regarded as preferential substrates for monoamine oxidase (MAO) type A. A close comparative examination of a number of tissues from different species, however, indicated the following differences. Serotonin was a more selective substrate for MAO-A, being inhibited by low concentrations (< 10^-7M) of the irreversible MAO-A inhibitor, clorgyline, more consistently and to a greater extent (80–100%) than was l-norepinephrine (30–85%). These serotonin-norepinephrine differences were greater in humans and other primates than in rodents. Serotonin also had a 2- to 4-fold smaller apparent K_m for MAO-A than l-norepinephrine and was deaminated 2- to 5-fold more readily by MAO in vitro in most tissues. In contrast, the MAO-B in human platelets deaminated l-norepinephrine more readily than serotonin. Thus, l-norepinephrine, like dopamine, should be regarded as a substrate for both MAO-A and MAO-B in vitro. The prominent role of MAO-B in norepinephrine degradation in primates may need to be considered in interpreting laboratory and clinical studies of clorgyline selective MAO-inhibiting drugs.