Pioglitazone, an Insulin Sensitizing Drug, Attenuates the Development of Kidney and Liver Disease in the PCK Rodent Model of Polycystic Kidney Disease

poster abstractPolycystic kidney disease is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney and liver. The only treatment currently available is the removal/aspiration of the largest cysts or organ transplantation. Promising pharmaceutical agents in clinical trials interfere with the action of hormones that increase cAMP thereby inhibiting secretion of Cl-, and compensatory fluid flux, into the cysts. Other treatments proposed include chemotherapeutic and immunosuppressive drugs that interfere with cellular proliferation as well as with signaling pathways for Cl- secretion. Long-term use of these agents will have multiple side effects. Based on a recent observation that peroxisome proliferator activated receptor γ agonists such as Actos (pioglitazone) and Avandia (rosiglitazone) decrease mRNA levels of a Cl- transport protein and the Cl- secretory response to vasopressin stimulation in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7 or 14 week feeding regimen of 20 mg/Kg BW pioglitazone inhibits renal and hepatic bile duct cyst growth in a rodent model orthologous to human PKD. In addition, the degree of renal cortical fibrosis was diminished in the pioglitazone-treated animals after 14 weeks. These results suggest that PPARγ agonists may be effective in controlling both renal and hepatic cyst growth and renal fibrotic development in polycystic kidney disease

Finite Nuclei in a Relativistic Mean-Field Model with Derivative Couplings

We study finite nuclei, at the mean-field level, using the Zimanyi-Moskowski model and one of its variations (the ZM3 model). We calculate energy levels and ground-state properties in nuclei where the mean-field approach is reliable. The role played by the spin-orbit potential in sorting out mean-field model descriptions is emphasized.Comment: 17 pages, 9 figures, 30 kbytes. Uses EPSF.TEX. To appear in Zeit. f. Phys. A (Hadrons and Nuclei

Pioglitazone Attenuates Cystic Burden in the PCK Rodent Model of Polycystic Kidney Disease

Polycystic kidney disease (PKD) is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney tubules and liver bile ducts. Currently, the clinical management of PKD is limited to cyst aspiration, surgical resection or organ transplantation. Based on an observation that PPARγ agonists such as pioglitazone and rosiglitazone decrease mRNA levels of a Cl− transport protein, CFTR (cystic fibrosis transmembrane conductance regulator), and the Cl− secretory response to vasopressin in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7- or 14-week pioglitazone feeding regimen inhibits renal and hepatic bile duct cyst growth in the PCK rat, a rodent model orthologous to human PKD. These studies provide proof of concept for the mechanism of action of the PPARγ agonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD

Derivative-Coupling Models and the Nuclear-Matter Equation of State

The equation of state of saturated nuclear matter is derived using two different derivative-coupling Lagrangians. We show that both descriptions are equivalent and can be obtained from the sigma-omega model through an appropriate rescaling of the coupling constants. We introduce generalized forms of this rescaling to study the correlations amongst observables in infinite nuclear matter, in particular, the compressibility and the effective nucleon mass.Comment: 16 pages, 6 figures, 36 kbytes. To appear in Zeit. f. Phys. A (Hadrons and Nuclei

Search for an annual modulation of dark-matter signals with a germanium spectrometer at the Sierra Grande Laboratory

Data collected during three years with a germanium spectrometer at the Sierra Grande underground laboratory have been analyzed for distinctive features of annual modulation of the signal induced by WIMP dark matter candidates. The main motivation for this analysis was the recent suggestion by the DAMA/NaI Collaboration that a yearly modulation signal could not be rejected at the 90% confidence level when analyzing data obtained with a high-mass low-background scintillator detector. We performed two different analyses of the data: First, the statistical distribution of modulation-significance variables (expected from an experiment running under the conditions of Sierra Grande) was compared with the same variables obtained from the data. Second, the data were analyzed in energy bins as an independent check of the first result and to allow for the possibility of a crossover in the expected signal. In both cases no statistically significant deviation from the null result was found, which could support the hypothesis that the data contain a modulated component. A plot is also presented to enable the comparison of these results to those of the DAMA collaboration.Comment: New version accepted by Astroparticle Physics. Changes suggested by the referee about the theoretical prediction of rates are included. Conclusions remain unaffected. 14 pages, LaTeX, 7 figures. Uses epsfig macr

QCD Sum Rules for Σ\Sigma Hyperons in Nuclear Matter

Within finite-density QCD sum-rule approach we investigate the self-energies of $\Sigma$ hyperons propagating in nuclear matter from a correlator of $\Sigma$ interpolating fields evaluated in the nuclear matter ground state. We find that the Lorentz vector self-energy of the $\Sigma$ is similar to the nucleon vector self-energy. The magnitude of Lorentz scalar self-energy of the $\Sigma$ is also close to the corresponding value for nucleon; however, this prediction is sensitive to the strangeness content of the nucleon and to the assumed density dependence of certain four-quark condensate. The scalar and vector self-energies tend to cancel, but not completely. The implications for the couplings of $\Sigma$ to the scalar and vector mesons in nuclear matter and for the $\Sigma$ spin-orbit force in a finite nucleus are discussed.Comment: 20 pages in revtex, 6 figures available under request as ps files, UMD preprint #94--11

Effect of calcium-sensing receptor activation in models of autosomal recessive or dominant polycystic kidney disease

Background. Antagonists of relevant Gs protein-coupled and agonists of relevant Gi protein-coupled receptors lower renal cAMP and inhibit growth of renal cysts in animal models of human ARPKD (PCK rat) and/or ADPKD (Pkd2−/WS25 mouse). A calcium-sensing receptor (CaR) is expressed in various tubular segments and couples to Gq, thereby activating phospholipase Cγ, InsP3 generation and calcium mobilization from intracellular stores, and Gi proteins. By both mechanisms, CaR activation could lower intracellular cAMP and inhibit renal cyst growth

Strangeness nuclear physics: a critical review on selected topics

Selected topics in strangeness nuclear physics are critically reviewed. This includes production, structure and weak decay of $\Lambda$--Hypernuclei, the $\bar K$ nuclear interaction and the possible existence of $\bar K$ bound states in nuclei. Perspectives for future studies on these issues are also outlined.Comment: 63 pages, 51 figures, accepted for publication on European Physical Journal

Experimental Search for Solar Axions via Coherent Primakoff Conversion in a Germanium Spectrometer

Results are reported of an experimental search for the unique, rapidly varying temporal pattern of solar axions coherently converting into photons via the Primakoff effect in a single crystal germanium detector. This conversion is predicted when axions are incident at a Bragg angle with a crystalline plane. The analysis of approximately 1.94 kg.yr of data from the 1 kg DEMOS detector in Sierra Grande, Argentina, yields a new laboratory bound on axion-photon coupling of $g_{a\gamma \gamma} < 2.7\cdot 10^{-9}$ GeV$^{-1}$, independent of axion mass up to ~ 1 keV.Comment: RevTeX, 11 pages, figures can be obtained by fax from [email protected]. Submitted to Phys. Lett.