Identification of Ion Transport Compartments in Turtle Urinary Bladder

To identify the turtle urinary bladder cells involved in Na and Cl absorption and Hand HCO3 secretion cellular electrolyte concentrations and uptake of Br and Solutrast were determined using electron microprobe analysis. Whereas inhibition of transepithelial Na transport by ouabain (reversion of short circuit current) led to a pronounced K-Na exchange in granular, and most of the basal cells, surface CA-cells and some basal cells were ouabain insensitive. Surface CA-cells could be divided into a large Cl-rich and a small Cl-poor population. Since the ouabain-induced K-Na exchange could be completely prevented by blocking passive luminal Na entry by amiloride, granular and most of the basal cells seem to form a syncytial Na transport compartment. Luminal uptake of Br only occurred in Cl-poor surface CA-cells, indicating the sole responsibility of these cells for electrogenic and electroneutral Cl absorption and HCO3 secretion. Serosal Br was taken up into all cell types. Whereas H secretion and serosal Br uptake into all cell types could be inhibited by 4-isothiocyano-4\u27-acetamido-2,2\u27-disulfonic stilbene (SITS), blockade of H secretion by lowering luminal pH to 4.5 diminished Br uptake only in Cl-rich surface CA-cells. Theses results indicate: a) Only Cl-rich surface CA-cells have a serosal anion exchanger involved in H secretion and b) granular and basal cells also possess a serosal anion exchanger, possibly responsible for cellular pH regulation. Luminal endocytosis of the I-containing Solutrast was observed in apical regions of Cl-rich surface CA-cells after inhibition of H secretion, but not under steady-state conditions, indicating a transport related but not a constitutive endo-exocytosis

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Background: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors. Methods: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. Results: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. Conclusions: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results

Toward a more professional and practical medical education: a novel Central European approach

Heinz Drexel,1–4,* Alexander Vonbank,1–3,* Peter Fraunberger,3,5 Walter F Riesen,3 Christoph H Saely1–3 1Vorarlberg Institute for Vascular Investigation and Treatment, 2Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; 3Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; 4Drexel University College of Medicine, Philadelphia, PA, USA; 5Medical Central Laboratories, Feldkirch, Austria  *These authors contributed equally to this work Abstract: We here present an innovative curriculum for a complete medical education that conforms to the current European Bologna system of academic training. The curriculum aims at raising doctors who are excellently prepared for clinical work over as short a time as 5 years; it provides a comprehensive, yet shorter than usual, education that strongly pronounces the importance of increasing the students’ practical clinical competences and rigorously excludes superfluous contents. The curriculum encompasses 52 modules, 32 at the bachelor’s and 20 at the master’s level. Already at the level of the bachelor degree, full employability is given; the students finish the master’s course as medical doctors optimally prepared to manage patients at the level of postgraduate medical education. The structure of the curriculum is modular; each modular component is essential for medical education and contains an average of five European Credit Transfer System credits, amounting to 150 hours of education. Depending on the subspecialty, the courses include lectures, seminars, practical laboratory training, and clinical training at varying quantities. In addition to attendance times, sufficient time slots are prepared for self-study in lectures, seminars, and practical work. With our curriculum, we provide an easily applicable backbone for a modern course of medicine that can be installed also at smaller academic institutions. Keywords: Bologna criteria, medical education, bedside teaching, practical medical education&nbsp

Specific-Heat Measurements on UBe₁₃ under Uniaxial Pressure

We have investigated the superconducting ground state of a high-quality UBe13 single crystal under uniaxial pressure along the [110] axis. Uniaxial pressure is expected to break the cubic symmetry and, perhaps, to remove orbital degeneracies associated with a multidimensional order parameter. However, our specific-heat measurements reveal no splitting of the superconducting transition at T(c) up to 6.8 kbar. Both T(c) (congruent-to 0.72 K) and the Sommerfeld coefficient gamma(congruent-to 1 J/k2 mole) decrease with increasing pressure, but the slopes disagree with the 1/3 rule of the hydrostatic values, as determined for polycrystalline samples

Cytokine production precedes the expansion of CD14+CD16+ monocytes in human sepsis: a case report of a patient with self-induced septicemia

We describe a patient with self-induced disease who presented with repeated urinary tract infection and sepsis due to intravesical and intravenous injection of feces. Sepsis occurred repeatedly such that the patient exhibited 10 bouts of fever > 40 degrees C in a single month. This bacterial challenge led to massive activation of the monocyte system with high levels of TNF-alpha, IL-6, and monocyte colony-stimulating factor (M-CSF). This cytokine response was followed by strong expansion of the novel CD14+CD16+ monocyte subset. These results suggest that cytokines induce the development of CD14+CD16+ cells in human septicemia and that CD14+CD16+ cells may serve as indicator for previous bouts of excessive inflammation