Atrial natriuretic peptide in heart failure

AbstractAtrial natriuretic peptide is a peptide hormone of cardiac origin, which is released in response to atrial distension and serves to maintain sodium homeostasis and inhibit activation of the reninangiotensin-aldosterone system. Congestive heart failure is a clinical syndrome characterized by increased cardiac volume and pressure overload with an inability to excrete a sodium load, which is associated with increased activity of systemic neurohumoral and local autocrine and paracrine mechanisms. Circulating atrial natriuretic peptide is greatly increased in congestive heart failure as a result of increased synthesis and release of this hormone. Atrial natriuretic peptide has emerged as an important diagnostic and prognostic serum marker in congestive heart failure. In early heart failure, it may play a key role in preserving the compensated state of asymptomatic left ventricular dysfunction. Despite increased circulating atrial natriuretic peptide in heart failure, the kidney retains sodium and is hyporesponsive to exogenous and endogenous atrial natriuretic peptide. The mechanism for the attenuated renal response is multifactorial and includes renal hypoperfusion, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. Therapeutic strategies to potentiate the biologic actions of atrial natriuretic peptide may prolong the asymptomatic phase and delay progression to overt congestive heart failure

The fate of the unexpected positive intraoperative cultures after revision total knee arthroplasty

Of a consecutive series of 692 revision total knees at 3 centers, intraoperative cultures were unexpectedly found to be positive in 41 cases (5.9%). Of the 41, 29 (71%) cases had a single positive intraoperative culture and were determined to be a probable false positive based on absence of any other evidence of infection, of which 5 were treated with extended course of intravenous antibiotics after hospital discharge and the remaining 24 received no further treatment. None of these 24 patients manifested any sign of infection at follow-up, averaging 46 months (range, 24-74 months). Twelve patients were determined to have probable type 1 periprosthetic infection, 11 of which were treated with a course of antibiotics. Two of these patients became reinfected within a year. A single positive intraoperative culture after revision total knee arthroplasty does not mandate further treatment in the absence of any other signs of infection

Food safety regimes in Scotland, 1899-1914

No abstract available

MANP Activation Of The cGMP Inhibits Aldosterone Via PDE2 And CYP11B2 In H295R Cells And In Mice

Background: Aldosterone is a critical pathological driver for cardiac and renal diseases. We recently discovered that mutant atrial natriuretic peptide (MANP), a novel atrial natriuretic peptide (ANP) analog, possessed more potent aldosterone inhibitory action than ANP in vivo. MANP and natriuretic peptide (NP)-augmenting therapy sacubitril/valsartan are under investigations for human hypertension treatment. Understanding the elusive mechanism of aldosterone inhibition by NPs remains to be a priority. Conflicting results were reported on the roles of the pGC-A (particulate guanylyl cyclase A receptor) and NP clearance receptor in aldosterone inhibition. Furthermore, the function of PKG (protein kinase G) and PDEs (phosphodiesterases) on aldosterone regulation are not clear. Methods: In the present study, we investigated the molecular mechanism of aldosterone regulation in a human adrenocortical cell line H295R and in mice. Results: We first provided evidence to show that pGC-A, not NP clearance receptor, mediates aldosterone inhibition. Next, we confirmed that MANP inhibits aldosterone via PDE2 (phosphodiesterase 2) not PKG, with specific agonists, antagonists, siRNA silencing, and fluorescence resonance energy transfer experiments. Further, the inhibitory effect is mediated by a reduction of intracellular Ca2+ levels. We then illustrated that MANP directly reduces aldosterone synthase CYP11B2 (cytochrome p450 family 11 subfamily b member 2) expression via PDE2. Last, in PDE2 knockout mice, consistent with in vitro findings, embryonic adrenal CYP11B2 is markedly increased. Conclusions: Our results innovatively explore and expand the NP/pGC-A/3',5', cyclic guanosine monophosphate (cGMP)/PDE2 pathway for aldosterone inhibition by MANP in vitro and in vivo. In addition, our data also support the development of MANP as a novel ANP analog drug for aldosterone excess treatment

Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

AbstractRisperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism