Collection of Wound Exudate From Human Digit Tip Amputations Does Not Impair Regenerative Healing: A Randomized Trial

The regrowth of amputated digit tips represents a unique regenerative healing in mammals with subcutaneous volume regrowth, restoration of dactylogram, and suppression of scar formation. Although factor analysis in amphibians and even in mice is easy to obtain, safety of harvesting biomaterial from human digit tip amputations for analysis has not yet been described.The aim of this study was to evaluate if recovering wound exudate does hamper clinical outcome or influence microbiologic or inflammation status.A predefined cohort of 18 patients with fresh digit tip amputations was randomly assigned to receive standard therapy (debridement, occlusive dressing) with (n = 9) or without (n = 9) collection of the whole wound exudate in every dressing change. Primary endpoint (lengthening) and secondary endpoints (regeneration of dactylogram, nail bed and bone healing, time to complete wound closure, scar formation, 2-point discrimination, microbiologic analysis, inflammatory factors interleukin (IL)-1α, tumor necrosis factor-α, IL-4, and IL-6) were determined by an independent, blinded observer.Patients’ characteristics showed no significant differences between the groups. All patients completed the study to the end of 3 months follow-up. Exudate collection did not influence primary and secondary endpoints. Furthermore, positive microbiologic findings as well as pus- and necrosis-like appearance neither impaired tissue restoration nor influenced inflammatory factor release.Here, the authors developed an easy and safe protocol for harvesting wound exudate from human digit tip amputations. For the first time, it was shown that harvesting does not impair regenerative healing. Using this method, further studies can be conducted to analyze regeneration associated factors in the human digit tip.DRKS.de Identifier: DRKS00006882 (UTN: U1111-1166-5723).     

Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Possible mechanisms of morphine analgesia.

The body has an endogenous analgesic system that prevents excess pain from interfering with the normal body functions. Depression of pain sensations occurs within the dorsal horn of the spinal cord where the primary pain fibers, which transmit pain sensations from the periphery, synapse with neurons that transmit pain to the higher centers. There appear to be two mechanisms by which the transmission of pain sensations are depressed; these include hyperpolarization of interneurons within the dorsal cord and depressing the release of the neurotransmitters associated with pain transmission. Activation of the analgesic mechanisms results from an interaction between specific neurotransmitters, such as enkephalin, serotonin, or norepinephrine, and specific receptors located on the neurons that transmit pain. The spinal analgesic mechanisms can be activated by either pain or nonpainful sensations arriving from the periphery or by supraspinal mechanisms. The supraspinal mechanisms originate in specific structures within the brainstem that include the periaqueductal gray matter, locus ceruleus, and nuclei in the medulla. These systems are activated either by ascending pain impulses or by higher centers such as the cortex or hypothalamus that, in turn, activate the spinal analgesic systems. There are three systems associated with activation of the supraspinal mechanisms. These include the opioid system associated with the release of the endorphins, the adrenergic system associated with the release of norepinephrine, and the serotonergic system associated with the release of serotonin. The interaction between these systems activates the spinal analgesic system. When the endogenous analgesic systems fail to control pain, analgesic drugs can be used to enhance the endogenous systems. Opiate drugs, such as morphine, interact with opioid receptors and produce analgesia by the same mechanisms as enkephalin, i.e., hyperpolarization of interneurons and depressing the release of transmitters associated with transmission of pain. In addition, morphine can interact with opioid receptors located in the supraspinal structures and activate the supraspinal system. Adrenergic drugs that interact with specific receptors also produce analgesia and it has been suggested that morphine interacts with the adrenergic system to produce analgesia.