The role of EGF-stimulated epidermis in the regulation of wound healing

Sluggish wounds are characterized by impaired proportions of proinflammatory cytokines, deficiency of fibrogenic growth factors, imbalance in the system of matrix metalloproteinases and their inhibitors this preventing reparation. The study was made of biopsies obtained from patients with sluggish wounds before the treatment, 5, 10 and 15 days after transplantation on the wound of allogenic EGF-stimulated cryopreserved epidermis. The wound closure with biologically active coat was followed by the reduction of expression of proinflammatory cytokines and return to their normal correlations, higher production of fibrogenic growth factors, restoration of balance in the expression of MMP-9 and TIMP-1/TIMP-2.     

The Implication of 1,3‐Dipolar Cycloaddition of Azomethine Ylides to the Synthesis of Main‐Chain Porphyrin Oligomers

The polycycloaddition of azomethine ylides to dipolarophiles is described for the first time. Use of (cis,cis)‐bis‐aziridines as a source of azomethine ylides allows selective polyaddition to be realized, which leads to oligomers exclusively with trans‐substituted pyrrolidine rings and modest molecular weights (ca. 5–10 kDa). The fluorescent, electrochemical, electrochromic, and non‐linear optical properties of the main‐chain free‐base porphyrin oligomer, synthesized by the developed procedure, are studied. An enhancement of the optical power limiting effect in a porphyrin oligomer solution is registered against that of the monomer.

     

Common clinical manifestations of serotonin deficiency and intoxication syndrome

Clinical manifestations of serotonin deficiency, its genesis, diagnostics, and treatment are described. the contribution of free hemoglobin and myoglobin to the genesis of absolute serotonin deficiency — disseminated intravascular coagulation (DIC) syndrome — is shown. Evidence is presented suggesting that chronic serotonin deficiency underlies aged-related and diabetic angiopathies. It is demonstrated that the serotonin deficiency syndrome has common clinical manifestations with the intoxication syndrome. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 604–613, June, 1997     

Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia,Russia, 2010 to 2019

European Journal of Clinical Microbiology & Infectious Diseases - Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical...     

Use of meningococcal vaccines in the United States

In January 2005, Food and Drug Administration licensed a new tetravalent (serogroups A, C, Y, W-135) meningococcal conjugate vaccine ([MCV4] Menactra) for use in persons 11-55 years of age. In February 2005, CDC's Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination of adolescents and college freshmen living in dormitories with MCV4. The manufacturer started shipments of MCV4 in March 2005. MCV4 should become a key addition to existing meningococcal disease prevention measures.     

Mechanism of suppression of physiological functions in hypothermia and means for their stimulation without body warming

Cold-suppressed thermoregulatory reactions and respiration in rats in deep hypothermia (rectal body temperature (25–22°C) were shown to be stimulated by injecting disodium ethylenediaminetetraacetic acid (EDTA) solution into the blood stream of cold rats at a dose of 16.5 mg/100 g (0.0045 mmol/100 g). EDTA binds Ca²⁺ ions in the blood, forming complexes. Increases in cold shivering and pulmonary respiration (by 5 min after the start of administration) coincided with a reduction in the blood Ca²⁺ concentration by 42–45% of normal. By 15 min after the start of the EDTA injection, the blood Ca²⁺ concentration returned to the normal level present in cold rats before EDTA treatment. This was accompanied by suppression of cold shivering and pulmonary respiration. Repeated injection of EDTA into the blood stream produced a new drop in blood Ca²⁺ and repeated stimulation of cold shivering and pulmonary respiration. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 11, pp. 1373–1381, November, 2006.     

Subtype-selective blockade of cardiac muscarinic receptors inhibits vagal chronotropic responses in cats

This study was designed to determine if chronotropic responses induced by neurally released acetylcholine are modified by subtype-selective blockade of cardiac muscarinic cholinoreceptors. In anesthetized cats, a single burst of vagal stimulation was generated with an incremental time delay after the P wave of the atrial electrogram (P-Stimulus interval). The slope of the relationships between P-Stimulus and P–P intervals was used to assess changes in responsiveness of cardiac pacemaker to vagal effects throughout the cardiac cycle. An increase in P-Stimulus interval over the initial portion (∼120 ms) of the cardiac cycle produced a significant increment in lengthening of the P–P interval. Once the maximal negative chronotropic response was achieved, a further increase in P-Stimulus interval by only ∼25 ms resulted in profound (by 80–90%) reductions in vagal effects, thus yielding a bimodal vagal phase response curve. Antagonists of M₁ (pirenzepine), M₂ (methoctramine and gallamine), and M₃ (4-DAMP) muscarinic cholinoreceptors produced a reduction in the magnitude of maximal lengthening of cardiac cycle as well as an increase in latency of vagal effects. However, the increment in prolongation of P–P interval induced by a given change in timing of vagal stimulation during cardiac cycle was reduced by M₁ and M₂ muscarinic receptor blockers, but was unaffected by 4-DAMP. None of the antagonists modified the range of P-Stimulus intervals over which the maximum-to-minimum change of vagal responses occurred. Taken together, these data suggest different contribution of various subtypes of cardiac muscarinic receptors into the negative chronotropic responses induced by brief bursts of vagal stimulation.     

ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile

Here, we describe novel mechanisms limiting a toxic cytosolic Ca²⁺ rise during adenosine 5′-triphosphate (ATP) depletion. We studied the effect of ATP depletion on Ca²⁺ signalling in mouse pancreatic acinar cells. Measurements of ATP in isolated cells after adenovirus-mediated expression of firefly luciferase revealed that the cytosolic ATP concentration fell from approximately 1 mM to near zero after treatment with oligomycin plus iodoacetate. ATP depletion resulted in the inhibition of Ca²⁺ extrusion, which was accompanied by a remarkably synchronous inhibition of store-operated Ca²⁺ influx. Alternative inhibition of Ca²⁺ extrusion by carboxyeosin had a much smaller effect on Ca²⁺ influx. The coordinated metabolic inhibition of Ca²⁺ influx and extrusion suggests the existence of a common ATP-dependent master regulator of both processes. ATP-depletion also suppressed acetylcholine (ACh)-induced Ca²⁺ oscillations, which was due to the inhibition of Ca²⁺ release from internal stores. This could be particularly important for limiting Ca²⁺ toxicity during periods of hypoxia. In contrast, metabolic control of Ca²⁺ influx and Ca²⁺ release from internal stores spectacularly failed to prevent large toxic Ca²⁺ responses induced by bile acids—activators of acute pancreatitis (a frequent and often fatal disease of the exocrine pancreas). The bile acids taurolithocholic acid 3-sulphate (TLC-S), taurochenodeoxycholic acid (TCDC) and taurocholic acid (TC) were used in our experiments. Neither Ca²⁺ release from internal stores nor Ca²⁺ influx triggered by bile acids were inhibited by ATP depletion, emphasising the danger of these pathological mechanisms. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Detection of low-frequency antigen-specific IL-10-producing CD4(+) T cells via ELISPOT in PBMC: cognate vs. nonspecific production of the cytokine

Single-cell resolution cytokine ELISPOT assays are increasingly used to gain insights into clonal sizes of type 1 and type 2 effector T cell populations in vivo. However, ELISPOT assays permitting monitoring of regulatory IL-10-producing T cells have so far not been established. Unlike IFN-gamma, IL-2, IL-4, and IL-5 assays performed on PBMC in which the recall antigen-induced cytokine spots are T cell-derived, we show here that in such assays IL-10 is primarily monocyte-derived. T cell-derived IL-10 spots were 80 x 10(3) microm(2) in size, seven times larger than spots produced by monocytes, and B cells produced even smaller spots. Based on spot size gating and the use of B cells as APC, we have established test conditions that permit measurement of cognate IL-10 production by low-frequency antigen-specific T cells. IL-10-producing PPD-specific CD4(+) T cells were detected in frequencies comparable to IFN-gamma-secreting CD4(+) T cells in tuberculosis patients, but not in uninfected healthy control individuals. In contrast, IL-10-secreting CD4(+) T cells specific for a panel of recall antigens could not be detected in frequencies >1/100,000 in healthy individuals whose CD4(+) cells responded to these antigens with type 1 or type 2 cytokine production in the 1:100,000-1:1000 frequency range. Therefore, the induction of IL-10-producing T cells seems to be under tighter control than that of Th1/Th2 cells, apparently confined to states of chronic immune stimulation. Access to low-frequency immune monitoring of IL-10-producing T cells will provide new insights into the role of regulatory T cells in health and disease.