The angiotensin II type 2 receptor: What is its clinical significance?

Angiotensin (Ang) II exerts its important physiologic functions through two distinct receptor subtypes, the type 1 (AT1) and type 2 (AT2) receptors. AT1 and AT2 receptors have demonstrated counterregulatory interactions in the cardiovascular and renal systems. The cross-talk between AT1 and AT2 receptors has been suggested to participate in regulating blood pressure, cardiovascular growth, fibrosis, and remodeling, as well as renal blood flow, growth, fibrosis, and sodium excretion. The AT1 receptor is distributed ubiquitously and abundantly in adult tissues, whereas expression of the AT2 receptor is high in the fetus but low in adult tissues. However, mounting evidence indicates that AT2 receptor cardiovascular expression increases in response to injury and AT1 receptor blocker therapy. This article reviews recent experimental and clinical data elucidating the role of the AT2 receptor in cardiovascular and renal homeostasis.     

Towards metabolically stable 5-HT7 receptor ligands: a study on 1-arylpiperazine derivatives and related isosters

Serotonin 7 (5-hydroxytryptamine7 or 5-HT₇) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT₇ receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1a) aimed at obtaining 5-HT₇ receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT₇ and 5-HT_1A receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine (2d) showed a good compromise between affinity at 5-HT₇ receptor (K _i = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT_1A receptor.     

The impact of noise on the reliability of heart-rate variability and complexity analysis in trauma patients

This study focused on the impact of noise on the reliability of heart-rate variability and complexity (HRV, HRC) to discriminate between different trauma patients and to monitor individual patients. Life-saving interventions (LSIs) were chosen as an endpoint because performance of LSIs is a critical aspect of trauma patient care. Noise was modeled and simulated by modifying original R–R interval (RRI) sequences via decimation, concatenation, and division of RRIs, as well as R-wave detection using the electrocardiogram. Results showed that under increasing simulated noise, entropy and autocorrelation measures can still effectively discriminate between LSI and non-LSI patients and monitor individuals over time.     

Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions

Odontology - Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to...     

Myocardial perfusion in real-time using power modulation. In vivo evidence for microcirculatory damage after acute myocardial infarction

BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received beta-radiation therapy as well as conventional therapy has also not been studied. METHODS: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. RESULTS: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/- 3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0 mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Delta EEM area between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/- 0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.     

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n?=?50) had significantly higher circulating levels of OPG as compared to control individuals (p?=?0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p?=?0.018) and was directly correlated with the amount of valve calcification (p?=?0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p?=?0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.     

Association of Sjögren's syndrome and rosacea: a diagnostic challenge

Both Sjögren's syndrome and rosacea present clinical manifestations that include ocular involvement. We report a case of a 45‐year‐old woman with a history of persistent erythematous malar rash, associated with conjunctival hyperemia, xerophthalmia and blefaritis. The patient filled the current classification criteria proposed for Sjögren's syndrome and those for rosacea. The coexistence of these diseases has not been previously described in the literature. Both diseases have similar symptoms and different treatment approaches. We believe that it is important for clinicians to identify this association in order to provide better care for the patient.