Telmisartan in the Treatment of Cohen-Rosenthal Diabetic Hypertensive Rats: The Benefit of PPAR-γ Agonism

The antihypertensive and hypoglycemic effects of telmisartan, which has dual angiotensin II antagonist-PPAR-γ agonist properties, was studied in Cohen-Rosenthal Diabetic Hypertensive rats (CRDH), a model in which hypertension, insulin resistance, and diabetes co-exist. CRDH, Cohen-diabetic rats (CDR), and SHR received telmisartan (3 mg/kg/day in drinking water) for five months. Telmisartan significantly lowered systolic and diastolic BP in SHR and CRDH, independent of body weight, and remained fairly constant in controls throughout the experiment. Blood glucose levels fell rapidly in the treated animals and remained steady in controls. Results indicate that telmisartan is a prototype of a new approach to treating coexisting diabetes and hypertension.     

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease

Purpose  

To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time.     

Direct activation of transient receptor potential V1 by nickel ions

TRPV1 is a member of the transient receptor potential (TRP) family of cation channels. It is expressed in sensory neurons of the dorsal root and trigeminal ganglia as well as in a wide range of non-neuronal tissues. The channel proteins serve as polymodal receptors for various potentially harmful stimuli to prevent tissue damage by mediating unpleasant or painful sensations. Using Ca imaging and voltage-clamp recordings, we found that low millimolar doses of Ni²⁺ (NiSO₄) are able to induce non-specific cation currents in a capsaicin-sensitive population of cultured mouse trigeminal ganglion neurons. In addition, we show that NiSO₄ elicits intracellular Ca²⁺ transients and membrane currents in HEK293 and CHO cells heterologously expressing rat TRPV1. The use of voltage ramps from ?100 to +100 mV revealed a strong outward rectification of these currents. Application of NiSO₄ to the cytoplasmic face of inside-out membrane patches did not induce any currents. However, delivering NiSO₄ to the extracellular face during outside-out recordings, we observed a significant increase in open probability paralleled by a decrease in channel conductance. When combined with other TRPV1 agonists, NiSO₄ produces a bimodal effect on TRPV1 activity, depending on the strength and concentration of the second stimulus. Outwardly directed currents induced by low doses of capsaicin and nearly neutral pH values (～pH?=?7.0–6.5) were augmented by low doses of NiSO₄. In contrast, responses to stronger stimuli were reduced by NiSO₄. Moreover, we were able to identify amino acids involved in the effect of NiSO₄ on TRPV1.     

Evaluation of a Records-Review Surveillance System Used to Determine the Prevalence of Autism Spectrum Disorders

We conducted the first study that estimates the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a population-based autism spectrum disorders (ASD) surveillance system developed at the Centers for Disease Control and Prevention. The system employs a records-review methodology that yields ASD classification (case versus non-ASD case) and was compared with classification based on clinical examination. The study enrolled 177 children. Estimated specificity (0.96, [CI_.95 = 0.94, 0.99]), PPV (0.79 [CI_.95 = 0.66, 0.93]), and NPV (0.91 [CI_.95 = 0.87, 0.96]) were high. Sensitivity was lower (0.60 [CI_.95 = 0.45, 0.75]). Given diagnostic heterogeneity, and the broad array of ASD in the population, identifying children with ASD is challenging. Records-based surveillance yields a population-based estimate of ASD that is likely conservative.