Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia.

Phosphatidylinositol 3-kinase catalytic subunit p110β is involved in tumorigenesis and hemostasis. However, it remains unclear if p110β also regulates platelet-mediated immune responses, which could have important consequences for immune modulation during anti-cancer treatment with p110β inhibitors. Thus, we investigate how platelet p110β affects inflammation and infection.

Radiotherapy for cervical cancer - impact on the vaginal epithelium and sexual function.

Background: Women who have been treated for cervical cancer have persistent changes in their sexual function, which result in considerable distress. The aim of this study was to investigate the morphology of the vaginal epithelium in cervical cancer survivors treated with radiotherapy and its correlation to serum levels of sex steroid hormones and sexual function.

Material And Methods: We included 34 patients treated for cervical cancer with radiotherapy and 37 healthy age-matched control women scheduled for benign gynecological surgery.

Radiotherapy-induced vaginal fibrosis in cervical cancer survivors.

Background: Cervical cancer survivors treated with radiotherapy report vaginal inelasticity and decreased lubrication that may affect their sexual health, but it is unknown which normal tissue reactions mediate these symptoms. The aim of this study was to investigate the morphology of the connective tissue of the vaginal wall in cervical cancer survivors treated with radiotherapy.

Material And Methods: We recruited 34 cervical cancer survivors treated with radiotherapy and 37 age-matched controls.

NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation.

Introduction: Large elevations of high sensitive Troponin T (hsTnT) in ischemic stroke patients is associated with a poor outcome. In a pilot study we found a high prevalence of malignancies among these patients. Since neutrophil extracellular traps (NETs) have been linked to cancer-associated thrombosis, we hypothesized that the concomitant cerebral and myocardial ischemia could be the result of a NET-induced hypercoagulable state.

Trousseau's Syndrome, a Previously Unrecognized Condition in Acute Ischemic Stroke Associated With Myocardial Injury.

Trousseau's syndrome is a well-known malignancy associated hypercoagulative state leading to venous or arterial thrombosis. The pathophysiology is however poorly understood, although multiple mechanisms are believed to be involved. We report a case of Trousseau's syndrome resulting in concomitant cerebral and myocardial microthrombosis, presenting with acute ischemic stroke and markedly elevated plasma troponin T levels suggesting myocardial injury.

Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies.

Tesaglitazar was developed as a dual peroxisome proliferator-activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals.

Proliferative and molecular effects of the dual PPARalpha/gamma agonist tesaglitazar in rat adipose tissues: relevance for induction of fibrosarcoma.

The dual peroxisome-proliferator-activated receptor (PPAR) α/γ agonist tesaglitazar has been shown to produce fibrosarcomas in rats. Here, the authors studied morphology, proliferation, differentiation, and inflammation markers in adipose tissue from rats exposed to 1, 3, or 10 µmol/kg tesaglitazar for 2 or 12 weeks, including recovery groups (12 weeks treatment followed by 12 weeks recovery), and 3 or 10 µmol/kg tesaglitazar for 24 weeks. Subcutaneous white and brown fat revealed reversible dose-related histopathological alterations and after 12 and 24 weeks developed areas of thickened skin (fatty lumps).

Delivering horseradish peroxidase as a respirable powder to the isolated, perfused, and ventilated lung of the rat: the pulmonary disposition of an inhaled model biopharmaceutical.

Background: Our aim was to investigate the potential of the DustGun aerosol technology integrated with the isolated, perfused, and ventilated lung of the rat (IPL) to study the pulmonary disposition of an inhaled model biopharmaceutical, the 40-kDa protein horseradish peroxidase (HRP).

Method: The DustGun aerosol technology was used to deliver respirable powder aerosols of HRP (the mass median aerodynamic diameter: 1.7 μm) as an 80-sec bolus to the IPL perfused in a single-pass mode.

Expression of angiopoietins 1, 2 and their common receptor tie-2 in relation to the size of endothelial lining gaps and expression of VEGF and VEGF receptors in idiopathic menorrhagia.

Objective: To investigate whether idiopathic menorrhagia (IM) is associated with alterations of the vascular expression of angiopoietin-1, angiopoietin-2, and tie-2 receptor.

Design: Prospective clinical study.

Setting: University Hospital, Department of Gynecology.

Histological inflammatory response to transvaginal polypropylene mesh for pelvic reconstructive surgery.

Purpose: We prospectively evaluated the histological inflammatory response to the large polypropylene transvaginal mesh used for pelvic organ prolapse surgery.

Materials And Methods: Ten patients and 8 controls underwent vaginal punch biopsy sampling before surgery and patients also underwent it 1 year after pelvic reconstructive surgery using polypropylene mesh. Foreign body response to the mesh was assessed using a combination of histological, semiquantitative and computerized image based analysis.

Steroid receptor expression and morphology in provoked vestibulodynia.

Objective: This study was undertaken to survey the steroid receptor expression and morphology in the vulvar vestibular mucosa in women with provoked vestibulodynia.

Study Design: Fourteen patients and 25 controls without oral contraceptives were included. Vestibular biopsy specimens were obtained and analyzed by using immunohistochemistry, followed by computerized image analysis of estrogen receptors alpha and beta, progesterone receptors A and B, glucocorticoid receptor, androgen receptor, and the proliferation marker Ki67.

Expression of vascular endothelial growth factor receptor-3 in the endometrium in menorrhagia.

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common gynecological disorders, including menorrhagia and endometriosis. We have recently shown that expression of vascular endothelial growth factor (VEGF)-A and its two main receptors, VEGFR-1 and -2, is increased in idiopathic menorrhagia (IM). The aim of this study was to determine the expression of VEGFR-3 in normal and IM endometrium.

A novel method for quantification of the folding of elastic laminae in elastic arteries.

A transgenic mouse overexpressing the human form of semicarbazide-sensitive amine oxidase (SSAO) is known to have an abnormal structure of the elastic laminae and the elastic fibres in the aorta. Compared to the non-transgenic littermates, the elastic laminae are less folded. In order to quantify the undulation of this structure, an image analysis program that identified the elastic laminae was developed.

Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats.

The development of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist tesaglitazar as an oral antidiabetic was recently discontinued. Here we present tumor data from a 2-year carcinogenicity study in rats given 0.3, 1, 3, and 10 micromol/kg tesaglitazar is presented with focus on the findings of subcutaneous fibrosarcomas.

Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia.

Objective: To investigate whether the structure or regulation of the growth of endometrial blood vessels might be abnormal in women with idiopathic menorrhagia (IM). Perturbation of angiogenesis is associated with IM.

Design: Prospective, clinical study.

Increasing exposure levels cause an abrupt change in the absorption and metabolism of acutely inhaled benzo(a)pyrene in the isolated, ventilated, and perfused lung of the rat.

The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are active primarily at the site of entry to the body. Lung cancer following inhalation of PAH-containing aerosols such as tobacco smoke is one likely example. A suggested mechanism for this site preference is a slow passage of the highly lipophilic PAHs through the thicker epithelia of the conducting airways, accompanied by substantial local metabolism in airway epithelium.

Microvascular density, vascular endothelial growth factor A, and its receptors in endometrial blood vessels in patients with menorrhagia.

Objective: To analyze the expression of vascular endothelial growth factor A (VEGF-A) and receptors (VEGFR-1 and VEGFR-2) in endometrial blood vessels, as well as microvascular density (MVD), in endometrial biopsy samples from idiopathic menorrhagia patients.

Design: Prospective clinical study.

Setting: University hospital, unit of gynecology.

Phenytoin teratogenicity: hypoxia marker and effects on embryonic heart rhythm suggest an hERG-related mechanism.

Background: The antiepileptic drug phenytoin (PHT) is a human and animal teratogen. The teratogenicity has been linked to PHT-induced embryonic cardiac arrhythmia and hypoxic damage during a period when regulation of embryonic heart rhythm is highly dependent on a specific K(+) ion current (I(Kr)). PHT has been shown to inhibit I(Kr).

Clinical and histological safety assessment of rectocele repair using collagen mesh.

Aim: To clinically and histologically evaluate inflammatory response following rectocele repair using porcine collagen mesh.

Methods: Seventeen patients underwent rectocele repair using porcine collagen mesh. Inflammatory response was assessed by clinical and histological inflammatory grading pre- and postoperatively.

A computerised, unbiased method for epithelial measurement.

Objective: To develop and evaluate a standardised method for unbiased measurements of epithelial thickness taking the variability of the dermal papillae in consideration.

Methods: A computer-assisted measurement program suitable for haematoxylin and eosin routine stained specimens has been developed.

Results: The developed program was designed to measure four different distance parameters, taking the number, height and width of dermal papillae into account.

Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia.

The rapid component of the delayed rectifying potassium ion current (IKr), plays an important role in cardiac repolarization. In rats, potent IKr channel blocking drugs cause similar stage-specific malformations (such as orofacial clefts and digital reductions) on gestational days (GDs) 10-14 as after periods of embryonic oxygen deprivation (hypoxia). The idea of a hypoxia-related teratogenic mechanism is supported by studies using rat embryos cultured in vitro.