Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process.

We have examined the effect of a synthetic analogue of human alpha-atrial natriuretic peptide (ANP), APII, on renin release in cultured renal juxtaglomerular cells (JGA cells). Using cell cultures containing 80-90% renal juxtaglomerular cells, we found that ANP (10(-13)-10(-9) M) strongly inhibited renin release from the cells in a dose-dependent fashion (ki, 10 pM) to about 10% of control. Inhibition of renin release by ANP was paralleled by an increase in cellular cGMP levels; while in the presence of the cGMP-phosphodiesterase inhibitor M&B 22948 (1 mM), concentrations of ANP lower by a factor of 100 were required to obtain the same effects on renin release and cGMP levels. The guanylate cyclase inhibitor methylene blue (10 microM), on the other hand, shifted the dose-response curves for renin release and cGMP levels to 100-fold higher concentrations of ANP. Neither the influx of 45Ca into the cells nor the intracellular quin-2 signal, which is a measure for changes of intracellular Ca concentration, was in any way altered by ANP. Our results suggest that ANP inhibits renin release from juxtaglomerular cells by a cGMP-dependent process that does not involve changes in intracellular calcium.     

Increasing atrial fibrillation: What is the cause?

A 72‐year‐old woman with a history of paroxysmal atrial fibrillation (AF) and sinus node dysfunction is seen in clinic for routine follow‐up.     

Effect that an educational program for cystic fibrosis patients and caregivers has on the contamination of home nebulizers

OBJECTIVE:

To describe the pathogens found in home nebulizers and in respiratory samples of cystic fibrosis (CF) patients, and to evaluate the effect that a standardized instruction regarding cleaning and disinfection of nebulizers has on the frequency of nebulizer contamination.

METHODS:

We included 40 CF patients (22 males), all of whom used the same model of nebulizer. The median patient age was 11.2 ± 3.74 years. We collected samples from the nebulizer mouthpiece and cup, using a sterile swab moistened with sterile saline. Respiratory samples were collected by asking patients to expectorate into a sterile container or with oropharyngeal swabs after cough stimulation. Cultures were performed on selective media, and bacteria were identified by classical biochemical tests. Patients received oral and written instructions regarding the cleaning and disinfection of nebulizers. All determinations were repeated an average of two months later.

RESULTS:

Contamination of the nebulizer (any part) was detected in 23 cases (57.5%). The nebulizer mouthpiece and cup were found to be contaminated in 16 (40.0%) and 19 (47.5%), respectively. After the standardized instruction had been given, there was a significant decrease in the proportion of contaminated nebulizers (43.5%).

CONCLUSIONS:

In our sample of CF patients, nebulizer contamination was common, indicating the need for improvement in patient practices regarding the cleaning and disinfection of their nebulizers. A one-time educational intervention could have a significant positive impact.     

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis

Phospholipases are produced from bacterial pathogens causing very different diseases. One of the most intriguing aspects of phospholipases is their potential to interfere with cellular signaling cascades and to modulate the host-immune response. Here, we investigated the role of the innate and acquired immune responses elicited by Chlamydophila pneumoniae phospholipase D (CpPLD) in the pathogenesis of atherosclerosis. We evaluated the cytokine and chemokine production induced by CpPLD in healthy donors' monocytes and in vivo activated T cells specific for CpPLD that infiltrate atherosclerotic lesions of patients with C. pneumoniae antibodies. We also examined the helper function of CpPLD-specific T cells for monocyte matrix metalloproteinase (MMP)-9 and tissue factor (TF) production as well as the CpPLD-induced chemokine expression by human venular endothelial cells (HUVECs). We report here that CpPLD is a TLR4 agonist able to induce the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 in monocytes, as well as CXCL-9, CCL-20, CCL-4, CCL-2, ICAM-1, and VCAM-1 in HUVECs. Plaque-derived T cells produce IL-17 in response to CpPLD. Moreover, CpPLD-specific CD4(+) T lymphocytes display helper function for monocyte MMP-9 and TF production. CpPLD promotes Th17 cell migration through the induction of chemokine secretion and adhesion molecule expression on endothelial cells. These findings indicate that CpPLD is able to drive the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 by monocytes and to elicit a Th17 immune response that plays a key role in the genesis of atherosclerosis.