Host-Pathogen Interaction and Resistance Mechanisms in Dermatophytes.

Dermatophytes are widely distributed in the environment, with an estimated prevalence of 20-25% of the the global population yearly. These fungi are keratinophilic and keratinolytic and cause the infection of keratin-rich structures such as skin, hair, and nails. The pattern of this infectious disease covers a wide spectrum from exposed individuals without symptoms to those with acutely inflammatory or non-inflammatory, chronic to invasive, and even life-threatening symptoms.

Characterization of Populations from Cultured European Seabass and the Surrounding Marine Environment with Emphasis on . .

species are widely distributed and can be potentially pathogenic to aquatic organisms. In this study, we isolated spp. from environmental samples (seawater, sediment, and fish swabs) collected over a three-year period from a fish farm in Mali Ston Bay in the Adriatic Sea, Croatia, and assess their distribution.

Measuring Shapes with Desired Convex Polygons.

In this paper we have developed a family of shape measures. All the measures from the family evaluate the degree to which a shape looks like a predefined convex polygon. A quite new approach in designing object shape based measures has been applied.

A restrictive dose of crystalloids in patients during laparoscopic cholecystectomy is safe and cost-effective: prospective, two-arm parallel, randomized controlled trial.

Purpose: There are no evidence-based guidelines for volume replacement during surgical procedures such as laparoscopic cholecystectomy. However, the administration of a restrictive volume of crystalloids could be more cost-effective and safe. This trial aimed to determine the effectiveness and safety of a restrictive regimen of crystalloids in patients during laparoscopic cholecystectomy by analyzing its cost-effectiveness and 1-year morbidity rate.

The effect of various doses of infusion solutions on the endothelial glycocalyx layer in laparoscopic cholecystectomy patients.

Background: The endothelial glycocalyx is located on the luminal side of blood vessels and maintains vessel integrity. This study analysed how various dosages of infusion affected the secretion of atrial natriuretic peptide (ANP) and potential glycocalyx damage in patients undergoing laparoscopic cholecystectomy. We hypothesised that the liberal administration of Ringer's solution during the operation can cause iatrogenic hypervolemia with releasing of ANP and glycocalyx damage.

General versus spinal anaesthesia in proximal femoral fracture surgery - treatment outcomes.

Background: Proximal femoral fractures are a major public health problem because of the increasing proportion of elderly individuals in the general population. The mode of choice for anaesthesia in surgical treatment of these fractures is still debated in terms of better postoperative outcome. The aim of our study was to compare the effect of general over spinal anaesthesia on mortality in proximal femoral fracture surgery.

Total and cytosolic concentrations of twenty metals/metalloids in the liver of brown trout Salmo trutta (Linnaeus, 1758) from the karstic Croatian river Krka.

Total and cytosolic concentrations of twenty metals/metalloids in the liver of brown trout Salmo trutta (Linnaeus, 1758) were studied in the period from April 2015 to May 2016 at two sampling sites on Croatian river Krka, to establish if river water contamination with metals/metalloids downstream of Knin town has influenced metal bioaccumulation in S. trutta liver. Differences were observed between two sites, with higher concentrations of several elements (Ag, As, Ca, Co, Na, Se, Sr, V) found downstream of Knin town, whereas few others (Cd, Cs, Mo, Tl) were, unexpectedly, increased at the Krka River spring.

PRACTICAL CHRONIC PAIN ASSESSMENT TOOLS IN CLINICAL PRACTICE.

The aim of the study was to show the role of tools in the evaluation of chronic pain (CP) in general practitioner (GP) everyday clinical practice. The study was done by analyzing electronic database of the first visits of 1090 CP patients referred to the Pain Clinic of the Karlovac General Hospital, Karlovac, Croatia, by their GPs. All patient records were analyzed according to the cause of CP, strongest pain a week before the examination, quality of sleep, and the Patients' Global Impression of Change scale.

Secondary stroke in patients with polytrauma and traumatic brain injury treated in an Intensive Care Unit, Karlovac General Hospital, Croatia.

Traumatic brain injury (TBI) is divided into primary and secondary brain injury. Primary brain injury occurs at the time of injury and is the direct consequence of kinetic energy acting on the brain tissue. Secondary brain injury occurs several hours or days after primary brain injury and is the result of factors including shock, systemic hypotension, hypoxia, hypothermia or hyperthermia, intracranial hypertension, cerebral oedema, intracranial bleeding or inflammation.

Pharmacodynamics, pharmacokinetics and safety of GSK2190915, a novel oral anti-inflammatory 5-lipoxygenase-activating protein inhibitor.

Aim: To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of the 5-lipoxygenase-activating protein inhibitor, GSK2190915, after oral dosing in two independent phase I studies, one in Western European and one in Japanese subjects, utilizing different formulations.

Method: Western European subjects received single (50-1000 mg) or multiple (10-450 mg) oral doses of GSK2190915 or placebo in a dose-escalating manner. Japanese subjects received three of four GSK2190915 doses (10-200 mg) plus placebo once in a four period crossover design.

5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor.

The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J.

Circulating cytokine levels in acute pancreatitis-model of SIRS/CARS can help in the clinical assessment of disease severity.

The aim of our study was to evaluate the pro- and anti-inflammatory cytokine response during acute pancreatitis and its predictive value on severity of disease. A hospital-based prospective clinical study was conducted. Twenty patients with acute pancreatitis were enrolled during a 12-month period.

Resuscitation of a polytraumatized patient with large volume crystalloid-colloid infusions--correlation between global and regional hemodynamics: case report.

Aggressive large volume resuscitation is obligatory to achieve necessary tissue oxygenation. An adequate venous preload normalizes global hemodynamics and avoids multiorgan failure (MOF) and death in patients with multiple injuries. Large volume resuscitation is associated with complications in minimally monitored patients.

Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation.

We evaluated the in vivo pharmacological properties of AM803 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, a selective five-lipoxygenase-activating protein (FLAP) inhibitor, using rat and mouse models of acute inflammation. Oral administration of AM803 (1 mg/kg) resulted in sustained inhibition of ex vivo ionophore-challenged whole blood LTB4 biosynthesis with >90% inhibition for up to 12 h and an EC50 of approximately 7 nM. When rat lungs were challenged in vivo with calcium-ionophore, AM803 inhibited LTB4 and cysteinyl leukotriene (CysLT) production with ED50s of 0.

Heterocycle-substituted proline dipeptides as potent VLA-4 antagonists.

A variety of N-linked tertiary amines and heteroarylamines were examined at the 4-position of sulfonylated proline dipeptides in order to improve VLA-4 receptor off-rates and overcome the issue of CYP3A4 time-dependent inhibition of ester prodrugs. A tight-binding inhibitor 5j with a long off-rate provided sustained receptor occupancy despite poor oral pharmacokinetics.

5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor.

A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model.

Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3',5'-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist.

A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro.

Characterization of alpha(4)beta(1) (CD49d/CD29) on equine leukocytes: potential utility of a potent alpha(4)beta(1) (CD49d/CD29) receptor antagonist in the treatment of equine heaves (recurrent airway obstruction).

The purpose of this study was to characterize the alpha(4)beta(1) receptor (CD49d/CD29, very late antigen-4, VLA-4) on circulating equine leukocytes and to evaluate the intrinsic potency of an alpha(4)beta(1) receptor antagonist (Compound B) in the horse. Ultimately, these studies would allow us to determine the suitability of treating recurrent airway obstruction (RAO; heaves) affected horses by blocking the cellular recruitment of lymphocytes and neutrophils into the lung. The data demonstrates the alpha(4)beta(1) integrin is present on horse lymphocytes and neutrophils (fluorescence-assisted cell sorter, FACS) and can bind low molecular weight alpha(4)beta(1) antagonists (Compounds A and B) with high affinity.

A new convexity measure for polygons.

Abstract-Convexity estimators are commonly used in the analysis of shape. In this paper, we define and evaluate a new convexity measure for planar regions bounded by polygons. The new convexity measure can be understood as a "boundary-based" measure and in accordance with this it is more sensitive to measured boundary defects than the so called "area-based" convexity measures.