Body therapy versus treatment as usual among Danish veterans with PTSD: Study protocol for a randomised controlled trial combined with a qualitative study.

Background: Many veterans suffer from Post-Traumatic Stress Disorder (PTSD) after returning from military missions. This implies complex physical and psychosocial problems for veterans and their families. Treatment options today are primarily medically and psychologically founded but treatment response is incomplete.

[Diagnosing and treating post-traumatic stress disorder].

The post-traumatic stress disorder (PTSD) diagnosis has undergone large developments. With the changes in DSM-5 and the proposed changes in ICD-11, the two systems move in different directions. Treatment for PTSD is developing, but the evidence for the effect is lacking behind.

Nonclinical pharmacokinetic and pharmacodynamic characterisation of somapacitan: A reversible non-covalent albumin-binding growth hormone.

Objective: Somapacitan is an albumin-binding growth hormone derivative intended for once weekly administration, currently in clinical development for treatment of adult as well as juvenile GH deficiency. Nonclinical in vivo pharmacological characterisation of somapacitan was performed to support the clinical trials. Here we present the pharmacokinetic and pharmacodynamic effects of somapacitan in rats, minipigs, and cynomolgus monkeys.

Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia.

Objective: To directly compare aripiprazole once-monthly 400mg (AOM 400) and paliperidone palmitate once-monthly (PP) on the Heinrichs-Carpenter Quality-of-Life Scale (QLS), a validated health-related quality of life and functioning measure in schizophrenia.

Method: This 28-week, randomized, non-inferiority, open-label, rater-blinded, head-to-head study (QUALIFY) of AOM 400 and PP in adult patients (18-60 years) comprised oral conversion, initiation of AOM 400 or PP treatment, and continuation with intramuscular injections every 4weeks. The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements.

Systematic Review of Sexual Dysfunction Among Veterans with Post-Traumatic Stress Disorder.

Introduction: The clinical observations that many Vietnam veterans complained of sexual problems after returning from active duty have led to the question of a correlation between post-traumatic stress disorder (PTSD) and sexual dysfunction (SD).

Aim: The purpose of this review is to systematically review the current literature regarding SD in male veterans with PTSD.

Methods: A systematic literature search, primarily in PubMed, the Cochrane database, and PsycINFO, was conducted.

A thiol functionalized cryogel as a solid phase for selective reduction of a cysteine residue in a recombinant human growth hormone variant.

Site selective chemical modification is a preferred method, employed to prolong the circulation half-life of biopharmaceuticals. Cysteines have been used as attachment point for such modification, however, to be susceptible for chemical modification the involved thiol must be in its reduced form. Proteins often contain disulfides, which aid to maintain their tertiary structure and therefore must remain intact.

Use of health care services before and after a natural disaster among survivors with and without PTSD.

Objective: This study used a questionnaire to identify individuals who met criteria for posttraumatic stress disorder (PTSD) ten months after surviving a disaster and compared their use of health care services before and after the disaster with that of survivors who did not meet criteria for PTSD.

Methods: Ten months after the December 26, 2004, Southeast Asian tsunami, Danish tourists who had been in areas exposed to the disaster were mailed a questionnaire asking about demographic characteristics and exposure to the tsunami. The questionnaire included the PTSD Checklist, which measures symptoms of posttraumatic stress.

Exposure characteristics and peri-trauma emotional reactions during the 2004 tsunami in Southeast Asia--what predicts posttraumatic stress and depressive symptoms?

This study examined the impact of disaster-related stressors and peri-trauma emotional reactions on mental health 10 months after the 2004 Southeast Asian tsunami disaster in a sample of 660 Danish tourists evacuated from the disaster area. The estimated rates of posttraumatic stress disorder and depression were 10.2% and 6.

Tsunami-affected Scandinavian tourists: disaster exposure and post-traumatic stress symptoms.

Background: Studies of short- and long-term mental effects of natural disasters have reported a high prevalence of post-traumatic stress. Less is known about disaster-exposed tourists repatriated to stable societies.

Aims: To examine the association between exposure to the 2004 Southeast Asian tsunami and symptoms of post-traumatic stress in three Scandinavian tourist populations.

The course of adjustment disorder in Danish male conscripts.

Conscription has been employed for more than a century. To evaluate the course and fate of conscripts deemed mentally unfit for immediate continued service, a prospective questionnaire study of conscripts referred for mental evaluation was conducted. Questionnaires were completed at the time of enrollment, time of admittance for evaluation, time of discharge from their evaluation and at 1-year follow-up.

Residue 259 in protein-tyrosine phosphatase PTP1B and PTPalpha determines the flexibility of glutamine 262.

To study the flexibility of the substrate-binding site and in particular of Gln262, we have performed adiabatic conformational search and molecular dynamics simulations on the crystal structure of the catalytic domain of wild-type protein-tyrosine phosphatase (PTP) 1B, a mutant PTP1B(R47V,D48N,M258C,G259Q), and a model of the catalytically active form of PTPalpha. For each molecule two cases were modeled: the Michaelis-Menten complex with the substrate analogue p-nitrophenyl phosphate (p-PNPP) bound to the active site and the cysteine-phosphor complex, each corresponding to the first and second step of the phosphate hydrolysis. Analyses of the trajectories revealed that in the cysteine-phosphor complex of PTP1B, Gln262 oscillates freely between the bound phosphate group and Gly259 frequently forming, as observed in the crystal structure, a hydrogen bond with the backbone oxygen of Gly259.

Structure-based design of selective and potent inhibitors of protein-tyrosine phosphatase beta.

Protein-tyrosine phosphatases (PTPs) are considered important therapeutic targets because of their pivotal role as regulators of signal transduction and thus their implication in several human diseases such as diabetes, cancer, and autoimmunity. In particular, PTP1B has been the focus of many academic and industrial laboratories because it was found to be an important negative regulator of insulin and leptin signaling, and hence a potential therapeutic target in diabetes and obesity. As a result, significant progress has been achieved in the design of highly selective and potent PTP1B inhibitors.

Residue 182 influences the second step of protein-tyrosine phosphatase-mediated catalysis.

Previous enzyme kinetic and structural studies have revealed a critical role for Asp181 (PTP1B numbering) in PTP (protein-tyrosine phosphatase)-mediated catalysis. In the E-P (phosphoenzyme) formation step, Asp181 functions as a general acid, while in the E-P hydrolysis step it acts as a general base. Most of our understanding of the role of Asp181 is derived from studies with the Yersinia PTP and the mammalian PTP1B, and to some extent also TC (T-cell)-PTP and the related PTPa and PTPe.

A novel strategy for the development of selective active-site inhibitors of the protein tyrosine phosphatase-like proteins islet-cell antigen 512 (IA-2) and phogrin (IA-2beta).

Islet-cell antigen 512 (IA-2) and phogrin (IA-2beta) are atypical members of the receptor protein tyrosine phosphatase (PTP) family that are characterized by a lack of activity against conventional PTP substrates. The physiological role(s) of these proteins remain poorly defined, although recent studies indicate that IA-2 may be involved in granule trafficking and exocytosis. To further understand their function, we have embarked upon developing low-molecular-mass inhibitors of IA-2 and IA-2beta.

Imidazoline NNC77-0074 stimulates insulin secretion and inhibits glucagon release by control of Ca(2+)-dependent exocytosis in pancreatic alpha- and beta-cells.

We have investigated the effects of the novel imidazoline compound (+)-2-(2-(4,5-dihydro-1H-imidazol-2-yl)-thiopene-2-yl-ethyl)-pyridine (NNC77-0074) on stimulus-secretion coupling in isolated pancreatic alpha- and beta-cells. NNC77-0074 stimulated glucose-dependent insulin secretion in intact mouse pancreatic islets. No effect was observed at View Article and Find Full Text PDF

Ligand-induced conformational changes: improved predictions of ligand binding conformations and affinities.

A computational docking strategy using multiple conformations of the target protein is discussed and evaluated. A series of low molecular weight, competitive, nonpeptide protein tyrosine phosphatase inhibitors are considered for which the x-ray crystallographic structures in complex with protein tyrosine phosphatase 1B (PTP1B) are known. To obtain a quantitative measure of the impact of conformational changes induced by the inhibitors, these were docked to the active site region of various structures of PTP1B using the docking program FlexX.

Discovery and SAR of a novel selective and orally bioavailable nonpeptide classical competitive inhibitor class of protein-tyrosine phosphatase 1B.

Reversible phosphorylation and dephosphorylation of key proteins on tyrosine residues are important parts of intracellular signaling triggered by hormones and other agents. Recent knock-out studies in mice have identified PTP1B as a potential target for the treatment of diabetes and obesity. As a consequence, a number of academic and industrial groups are aggressively pursuing the development of selective PTP1B inhibitors.

Structure determination of T cell protein-tyrosine phosphatase.

Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided.