Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction.

Background: Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF.

Methods: 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation.

Randomised controlled trial with medical leeches for osteoarthritis of the knee.

Objectives: To evaluate the possible efficacy of medical leeches (Hirudo medicinalis) in the treatment of patients with active osteoarthritis of the knee.

Design: Unblinded, randomised controlled trial with outpatients in a crossover design with single interventions of either leeches or transcutaneous electrical nerve stimulation (TENS) as comparator.

Main Outcome Measures: Change in Lequesne's combined index for pain and function and change (L.

Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction.

Objectives: We attempted to correlate echocardiographic analysis of diastolic function with changes of myocardial collagen in middle-aged patients with heart failure (HF) despite normal ejection fraction (EF).

Background: Increased collagen deposition may contribute to the deterioration of the left ventricular compliance and diastolic dysfunction in HF.

Methods: We investigated 41 patients (median age 50 years [interquartile range: 41 to 57 years]) with normal EF (median 62% [interquartile range: 56% to 70%]) whose endomyocardial biopsies were taken previously.

Effects of electromagnetic fields emitted by mobile phones (GSM 900 and WCDMA/UMTS) on the macrostructure of sleep.

In the present double-blind, randomized, sham-controlled cross-over study, possible effects of electromagnetic fields emitted by Global System for Mobile Communications (GSM) 900 and Wideband Code-Division Multiple Access (WCDMA)/Universal Mobile Telecommunications System (UMTS) cell-phones on the macrostructure of sleep were investigated in a laboratory environment. An adaptation night, which served as screening night for sleep disorders and as an adjustment night to the laboratory environment, was followed by 9 study nights (separated by a 2-week interval) in which subjects were exposed to three exposure conditions (sham, GSM 900 and WCDMA/UMTS). The sample comprised 30 healthy male subjects within the age range 18-30 years (mean ± standard deviation: 25.

Comorbidities of hidradenitis suppurativa (acne inversa).

Comorbidities of hidradenitis suppurativa (acne inversa) were reviewed by extracting original and review publications included in MEDLINE, EMBASE and COCHRANE libraries using the terms "hidradenitis," "Verneuil" and "acne inversa." Follicular occlusion disorders, inflammatory bowel diseases, especially Crohn disease, spondylarthropathy, other hyperergic diseases, genetic keratin disorders associated with follicular occlusion and squamous cell carcinoma were the most common hidradenitis suppurativa comorbid diseases. A first classification of these major comorbidities and their possible genetic background reveals a list of chromosome loci and genes, which could be hidradenitis suppurativa candidates.

Dinucleoside polyphosphates and uremia.

Dinucleoside polyphosphates constitute a group of endogenous vasoregulatory purines and pyrimidines with a strong impact on physiologic and pathophysiologic processes of the cardiovascular system. Recently, the importance of dinucleoside polyphosphates in chronic kidney disease (CKD) and uremia gained increasing interest. Although our knowledge about the impact of dinucleoside polyphosphates in CKD and uremia is just at the beginning, this article reviews the current knowledge of the physiologic and pathophysiologic role of dinucleoside polyphosphates in CKD and uremia.

Dinucleoside polyphosphates: strong endogenous agonists of the purinergic system.

The purinergic system is composed of mononucleosides, mononucleoside polyphosphates and dinucleoside polyphosphates as agonists, as well as the respective purinergic receptors. Interest in the role of the purinergic system in cardiovascular physiology and pathophysiology is on the rise. This review focuses on the overall impact of dinucleoside polyphosphates in the purinergic system.

Differential infraslow (<0.1 Hz) cortical activations in the affected and unaffected hemispheres from patients with subacute stroke demonstrated by noninvasive DC-magnetoencephalography.

Background And Purpose: Sustained mass depolarization of neurons, termed cortical spreading depolarization, is one electrophysiological correlate of the ischemic injury of neurons. Cortical spreading depolarizations spread in the gray matter at a rate of approximately 3 mm/min and are associated with large infraslow extracellular potential changes (<0.05 Hz).

In utero transmission of porcine torque teno viruses.

Sera and selected tissue homogenates collected from gnotobiotic swine never exposed to the environment or other swine tissues were tested for the presence of porcine torque teno virus (TTV) DNAs by nested and non-nested polymerase chain reactions (PCR) using primers specific for the untranslated region of porcine genogroups (g) 1 and 2. Twenty-three of 105 (21.9%) gnotobiotic piglets were g1- and/or g2-TTV DNA positive.

Epstein-Barr virus-associated B-cell lymphoma secondary to FCD-C therapy in patients with peripheral T-cell lymphoma.

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders occur at an increasing frequency in various hereditary and acquired states of immune dysfunction. In a few cases of T-cell lymphoma, especially in angioimmunoblastic T-cell lymphoma (AILT), EBV-associated B-cell lymphoproliferative disorders have been reported. Here, we present two cases of EBV-associated B-cell lymphoma after treatment of T-cell lymphoma (AILT and peripheral T-cell lymphoma, unspecified, PTCL-NOS) with a regimen containing alemtuzumab and fludarabine.

Listing's plane and the otolith-mediated gravity vector.

The orientation of Listing's plane (LP) was examined under one-g and zero-g conditions during parabolic flight and during prolonged spaceflight. Ten healthy subjects participated in the parabolic flight study. In zero-g, the orientation of LP was consistently altered.

Ocular involvement is associated with HLA-B51 in Adamantiades-Behçet's disease.

Purpose: To evaluate the association of HLA-B51 and ocular involvement in Adamantiades-Behçet's disease.

Methods: We retrospectively analysed all patients with Adamantiades-Behçet's disease examined in our Department of Ophthalmology since 1982. All patients fulfilled the criteria of the International Study Group for Behçet's disease.

Negative-feedback loop attenuates hydrostatic lung edema via a cGMP-dependent regulation of transient receptor potential vanilloid 4.

Although the formation of hydrostatic lung edema is generally attributed to imbalanced Starling forces, recent data show that lung endothelial cells respond to increased vascular pressure and may thus regulate vascular permeability and edema formation. In combining real-time optical imaging of the endothelial Ca(2+) concentration ([Ca(2+)](i)) and NO production with filtration coefficient (K(f)) measurements in the isolated perfused lung, we identified a series of endothelial responses that constitute a negative-feedback loop to protect the microvascular barrier. Elevation of lung microvascular pressure was shown to increase endothelial [Ca(2+)](i) via activation of transient receptor potential vanilloid 4 (TRPV4) channels.

Uridine adenosine tetraphosphate acts as an autocrine hormone affecting glomerular filtration rate.

Recently, uridine adenosine tetraphosphate (Up(4)A) was described as a strong vasoconstrictor released from endothelial cells after stimulation with mechanical stress. In this study, we isolated and identified Up(4)A from kidney tissue, and we characterized the essential varying effects of Up(4)A on the afferent and efferent arterioles. Porcine and human kidney tissue was fractionated by size exclusion chromatography, affinity chromatography, anion exchange chromatography and reverse phase chromatography.

Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long-term bed rest with and without countermeasures.

The cellular mechanisms of human skeletal muscle adaptation to disuse are largely unknown. The aim of this study was to determine the morphological and biochemical changes of the lower limb soleus and vastus lateralis muscles following 60 days of head-down tilt bed rest in women with and without exercise countermeasure using molecular biomarkers monitoring functional cell compartments. Muscle biopsies were taken before (pre) and after bed rest (post) from a bed rest-only and a bed rest exercise group (n = 8, each).

Dynamics of cortical neurovascular coupling analyzed by simultaneous DC-magnetoencephalography and time-resolved near-infrared spectroscopy.

Functional magnetic resonance imaging (fMRI) visualizes activated brain areas with a high spatial resolution. The activation signal is determined by the local change of cerebral blood oxygenation, blood volume and blood flow which serve as surrogate marker for the neuronal signal itself. Here, the complex coupling between these parameters and the electrophysiologic activity is characterized non-invasively in humans during a simple motor task using simultaneously DC-magnetoencephalography (DC-MEG), for the detection of neuronal signals, and time-resolved near-infrared spectroscopy (trNIRS), for cortical metabolic/vascular responses: over the left primary motor cortex hand area of healthy subjects DC-fields and trNIRS parameters followed closely the 30 s motor task cycles, i.

Corticotropin-releasing hormone skin signaling is receptor-mediated and is predominant in the sebaceous glands.

There is increasing evidence that the sebaceous gland expresses receptors for several neuropeptides and is involved in responses to stress. Among them, corticotropin-releasing hormone (CRH) was currently found to be produced also in the skin. In this study, the distribution of CRH, CRH receptors 1 and 2 (CRH-R1 and CRH-R2), and CRH binding protein (CRH-BP) in cultured human (SZ95) sebocytes was further characterized.

Responsiveness to androgens and effectiveness of antisense oligonucleotides against the androgen receptor on human epidermal keratinocytes is dependent on the age of the donor and the location of cell origin.

Local androgen excess has been associated with attenuation of wound healing in elderly individuals and with a decline in permeability barrier homeostasis in adult human skin. In this study we have applied specific antisense oligonucleotides, whose activity has already been investigated in SZ95 sebocytes, to inactivate transiently the androgen receptor in a reconstituted epidermis model and in primary human epidermal keratinocytes of different origin (breast, abdomen, foreskin) and donor age (females, 30- and 60-year-old). Further a possible interaction between blockage of androgen receptor and the expression of tissue inhibitors of matrix metalloproteinases was investigated.

All-trans-retinoic acid and 13-cis-retinoic acid: pharmacokinetics and biological activity in different cell culture models of human keratinocytes.

Despite its known biological effect on epithelial cells, 13- CIS-retinoic acid shows low binding affinity to either cellular retinoic acid-binding proteins or nuclear retinoid receptors compared to its isomer all- TRANS-retinoic acid. We have postulated a prodrug-drug relation with 13- CIS-retinoic acid which isomerizes to all- TRANS-retinoic acid. On the other hand, the biological effects of these two compounds can differ in the widely used cell culture models of HaCaT and normal primary keratinocytes.

An update on Behçet's disease.

Behçet's disease (Adamantiades-Behçet's disease, ABD) is a multisystemic inflammatory disease, the pathogenesis of which is still a mystery. Many questions are still to be answered and the available diverse data need to be brought together to be compared and analysed. There is at least consensus on the effect of possible, but currently unknown, environmental triggering factor(s) against a background of genetic susceptibility.

Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure.

Background: Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF.

Methods: In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls.

Selectins revisited: the emerging role of platelets in inflammatory lung disease.

Neutrophil infiltration into the lung is considered a crucial step in the pathogenesis of acute lung injury, yet data on the underlying mechanisms have been ambiguous: although selectin-mediated leukocyte rolling is absent in lung capillaries, therapeutic strategies targeted at selectin-mediated cell-cell interactions yield partial protection. The study by Zarbock and coworkers in this issue of the JCI solves this apparent contradiction by identifying selectin-mediated platelet-neutrophil interaction as a critical step in the mutual activation of leukocytes and endothelial cells (see the related article beginning on page 3211). The emerging role of platelets may be of broad clinical relevance in lung inflammatory disorders, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node.

Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12.

Background And Aims: As integral membrane proteins, claudins form tight junctions together with occludin. Several claudins were shown to be up-regulated in various cancer types. We performed an expression analysis of genes encoding tight junction proteins to display differential gene expression on RNA and protein level and to identify and validate potential targets for colorectal cancer (CRC) therapy.