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[FORM AND CONTENT].

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Concept Formation↗

Experimental flexor tendon healing without adhesion formation--a new concept of tendon nutrition and intrinsic healing mechanisms. A preliminary report.

An experimental model is presented enabling an analysis of the healing process of completely cut and re-sutured free segments of rabbit flexor tendons, kept avascular in a synovial milieu and completely isolated from adhesion formation. Under these conditions the cut tendons heal within a few weeks. It can be shown that this healing process is a result of intrinsic tendon cell activity only.

Animals↗

Prevention of hydroxyl radical formation: a critical concept for improving cardioplegia. Protective effects of deferoxamine.

The hydroxyl radical is one of the most damaging oxygen metabolites that are thought to be produced during ischemia and reperfusion of cardiac tissue. Therefore, we used the isolated, isovolumetric, buffer-perfused rat heart preparation of cardioplegic arrest to assess the effects of interventions targeted at inhibiting production of the hydroxyl radical by decreasing either the availability of one of its precursors (hydrogen peroxide) or that of the metal catalyst (ferric iron) involved in the radical formation. Sixty hearts were studied and, except for nonischemic controls, were subjected to 3 hr of hypothermic (15 degrees to 18 degrees C) cardioplegic arrest, followed by 45 min of reperfusion. The following interventions were tested: pretreatment with peroxidase, a scavenger of hydrogen peroxide, pretreatment with a combination of peroxidase and the iron chelator deferoxamine, pretreatment with peroxidase followed by supplementation of the cardioplegic solution with deferoxamine, and supplementation of the cardioplegic solution with deferoxamine without preischemic enzymatic treatment. Based on comparisons of postreperfusion pressure development, maximal ventricular dP/dt, left ventricular compliance, and coronary flow, deferoxamine-containing cardioplegic solution alone afforded the best myocardial protection. This may be due to the ability of deferoxamine to act both as an iron chelator and as a direct scavenger of superoxide anion, an activated oxygen species that participates in hydroxyl radical formation. This study confirms that an important component of the cardiac damage sustained during global ischemia and reperfusion may involve injury caused by the hydroxyl radical. Furthermore, our results point out the potential therapeutic usefulness of deferoxamine in the context of cardioplegic protection during open-heart procedures.

Animals↗

Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formation.

The alkaloids 1',2'-didehydrostemofoline (2) and 2'-hydroxystemofoline (3) from Stemona collinsae Craib (Stemonaceae) were studied by X-ray crystallography and NMR spectroscopy, and they are compared with the parent compound stemofoline (1). The X-ray analysis of the CH2Cl2 solvate of 2'-hydroxystemofoline (3) allowed the determination of the absolute configuration of this compound unequivocally, whereas optical rotation was used to infer the absolute configuration of 1',2'-didehydrostemofoline (2). Based on these results, it is shown that asparagamine A isolated from Asparagus racemosus Willd. (Asparagaceae) is identical to 1',2'-didehydrostemofoline obtained from S. collinsae Craib, and that the reported plant source of asparagamine A was most likely a Stemona species. In the context of the current investigations, a novel concept on the biosynthesis of Stemona alkaloids has been worked out and is presented here.

Alkaloids↗

New concepts in the formation, regulation of release, and metabolism of parathyroid hormone.

New information has elucidated many of the biochemical pathways in the formation, release and metabolism of parathyroid hormone (PTH). The hormone is biosynthesized in the parathyroid cells from two distinct precursors, or prohormones, that are modified by specific enzymic cleavages during the synthesis and intracellular transport of the hormonal polypeptide. Release of the hormone from the gland inversely depends on the extracellular calcium concentration, but is regulated over a much narrower range of calcium concentration than was realized previously. This new information points to a pattern of regulation that is more appropriate for homeostasis than was the pattern indicated by earlier studies. The persistence of a basal level of PTH secretion, despite sustained hypercalcaemia, suggests a possible mechanism for the abnormal secretion seen in states of hyperparathyroidism. The discovery of a calium-dependent degradative pathway for PTH in the parathyroid cell indicates that changes in the turnover of PTH may be one means by which calcium regulates the amount of hormone available for secretion. Of the multiple immunoreactive forms of PTH present in the circulation of man and animals, the predominant form in blood appears to be a large biologically-inactive fragment consisting of the middle and carboxy two-thirds of the hormone sequence. At times, smaller biologically-active fragments of PTH may also appear in blood. Most circulating fragments of PTH probably arise from peripheral cleavage of the intact, secreted hormone in kidney and liver, but some forms of the hormone, including prohormones, may also be secreted from the parathyroid gland. The heterogeneity of circulating PTH and the concomitant uncertainties regarding its precise character have introduced difficulties in the interpretation of immunoassay measurements. A further delineation of the pathways and regulation of PTH biosynthesis, secretion and metabolism should lead to the development of more-specific immuno-assays and result in improved diagnosis and management of patients with disorders of the parathyroid glands.

Amino Acid Sequence↗

The response of rat tibiae to incremental bouts of mechanical loading: a quantum concept for bone formation.

To investigate the minimum number of loading bouts necessary to produce new lamellar or woven bone formation, and the time required for its initiation, bone formation was measured in 32 retired breeder female Sprague-Dawley rats following one, two, three, or five bouts of applied loading. Bending forces of 54 N were applied to right tibiae using a four-point loading apparatus, and left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per loading bout. Rats were injected with alizarin on day 1 and calcein on days 5 and 12, and were killed on day 19. One bout of loading was sufficient to increase the periosteal woven bone surface (Wb.Pm/B.Pm) from 0% to 40% (p < 0.01), and to 80% after five bouts of loading (p < 0.01), with a dose-response relationship for increases in Wb.Pm/B.Pm (p < 0.0001), mineral apposition rate (Wb.AR; p = 0.002), and bone formation rate (Wb.BFR/BS; p = 0.0001). In the first labeling period (days 1-5), the endocortical lamellar bone forming surface (BSf/BS) was increased slightly (p < 0.05), but no significant differences were shown for BFR/BS or MAR. From days 5 to 19, right tibiae showed a dose-response increase in BFR/BS (p = 0.002) and BSf/BS (p = 0.008), but not MAR. These results are consistent with a "quantum" model of bone formation such that a "quantum" of bone cells is activated in response to the loading bout and the strain magnitude dictate the size or microstructural organization of a given packet of new bone. Conversely, the distributed nature of loading may define the recruitment, rather than size, of new packets of bone.

Analysis of Variance↗