Characteristic of the endogenous enkephalin degrading enzymes inhibitors

Management of acute and chronic pain has always been a key area of clinical research. Pain and stress stimulation may cause an increase in the level of endogenous opioids in the body. Endogenous enkephalins activate opioid receptors in the brain, leading to the analgesic effect. Enkephalinases inactivate endogenous opioids, abolishing their activity. Enkephalin degrading enzyme inhibitors (EIs) in turn inhibit these enzymes, preventing them from degrading endogenous enkephalins what leads to analgesia. The enkephalin degrading enzyme inhibitors seem to be promising analgesic agents [2]. Analgesic effect of EIs has been discovered recently and their therapeutic potential has not been effectively investigated yet. The main advantage of enkephalinase inhibitors is that they do not show adverse effects characteristic for opioids. EIs play an important role in modulating nociception, so they are potential agents for the treatment of acute and chronic pain. They often possess also additional antidiarrheal, antidepressant and anticancer properties [3]. The potential EIs targets appear to be aminopeptidase N (APN), dipeptidyl peptidase III (DPP III), angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) [4]. EIs may be broadly classified as endogenous and those that are obtained synthetically [4]. The purpose of this work is to present a review of endogenous enkephalinase inhibitors: sialorphin, opiorphin, and spinorphin. Sialorphin (Gln-His-Asn-Pro-Arg) is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. Sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin prevents spinal and renal NEP from breaking down substance P and Met-enkephalin in vitro. Sialorphin suppressed pain sensation for both chemical- -induced inflammation and acute physical pain [8, 9, 12]. Opiorphin (Gln-Arg-Phe-Ser-Arg) is an endogenous chemical compound first isolated from human saliva. Opiorphin is a natural analgesic. Opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase N. Opiorphin is closely related to the rat sialorphin peptide [12, 13, 19]. Spinorphin (Leu-Val-Val-Tyr-Pro-Trp-Thr) has been isolated from the bovine spinal cord as an endogenous inhibitor of enkephalin - degrading enzymes. Spinorphin is an antagonist of the P2X3 receptor and a weak partial agonist/antagonist of the FP1 receptor [24, 25, 26]

Methods used to vizualize latent fingerprints

Dactyloscopy as one of the branches of forensic science deals with fingerprints identification of the individual human being. Fingerprints are in general invisible, therefore in order to set about the identification, we have to make them evident. To reveal hidden fingerprints, criminological technology uses physical methods, chemical reactions and even some biological processes. In this review, we present a set of methods that is being used in criminology to reveal fingerprints and other hidden traces. In search for potential fingerprints, objects are exposed to natural and artificial light sources since visual methods are most commonly used by criminology technicians. Further methods for revealing fingerprints are selected on the basis of type of surface, the trace was left on, and the substance forming the fingerprint. In his article we present the set of methods, commonly used to reveal fingerprints, featuring physical, chemical and physicochemical approaches [6]. Chemical methods: DFO, 1,2-IND and Ninhydin used for revealing fingerprints on absorptive surfaces, Amido Black, Hungarian Red, DAB and LCV used for detecting bloody fingerprints, DMAC used for revealing fingerprints on temperature-felt papers, RTX dioxide of ruthenium used to absorptive and nonabsorptive surfaces [9, 11, 14, 19, 22, 24, 26, 28, 30]. Next, we present physical methods among others optical methods which are helpful in revealing fingerprints for the naked eye and (if needed) enlarging optical devices. To achieve acceptable visibility, criminologists use various kinds of lamps and filters. Subsequently we present methods based on adhesion, that are based on adjoining the powder or suspension to sudoral-fatty substance. We present here methods based on the use of dactyloscopic powders, crystal violet which is appearing in the form of dark-green powder , SPR (Small Particle Reagent) – suspension of black MoS2 powder, Sticky-side Powder which composition is accessing iron oxide and aluminum, Wet Powder Black, composed of iron oxide and Wet Powder White (titanium dioxide). Tape-Glo (ready-made red-orange solution), Sudan Black B (in the solid state it is a powder of the black colour), Liquid-drox (yellow solution), fluorescent dyes: Ardrox P133D, Safranin O, chelate of europium and Basic Yellow 40 [31, 34–38]. The other methods are physicochemical methods: cyanoacrylate, iodine, physical developer and multi metal deposition [42, 45, 46]. As a result of technological development newer methods of visualizing latent fingerprints appear, replacing those previously used. Improvement of the methods of revealing latent fingerprints leads to better readability and in effect, makes police work easier

Cell-penetrating peptides : types and mechanisms of penetration

Before discovery of the Tat peptide over twenty years ago, it was assumed that large peptides and proteins do not penetrate cell membranes. After discovery of Tat, Penetratin [1, 2] and several other peptides of natural origin, able to cross the cell membranes in an energy-independent manner, the structural determinants of their cell-penetrating potency were established, including polycationic character, amphipaticity and presence of proline-rich motifs [3, 4]. Currently known cell-penetrating peptides of natural or synthetic origin are composed of 5 to 40 amino acid residues and belong to one of the three families: oligocationic, amphipatic or proline-rich and penetrate the biological membranes by endocytosis or other ways of direct translocation. Most of these translocation mechanisms are not exclusive and may occur simultaneously, and their contribution may be different for each peptide depending on the conditions (e.g. CPP concentration, pH, etc.). Most CPPs demonstrate little or no mammalian cell toxicity what makes them promising vectors for drug delivery. Such vectors might be useful for efficient internalization of compounds otherways poorly penetrating biological membranes. Novel CPP-effector conjugates may become effective anticancer or antimicrobial agents of a great potential for chemotherapy [3, 5]. In this short review we present a glimpse at the current state of knowledge concerning sub‑families, types and mechanisms of action of most prominent members of CPP family