Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the G{alpha}q/11 pathway

MrgA1 and MrgC11 belong to a recently identified family of orphan G-protein coupled receptors, called mrgs (mas-related genes). They are only expressed in a specific subset of sensory neurons that are known to detect painful stimuli. However, the precise physiological function of Mrg receptors and their underlying mechanisms of signal transduction are not known. We therefore have screened a series of neuropeptides against human embryonic kidney (HEK) 293 cells that stably express either MrgA1 or MrgC11 to identify ligands and/or agonists. MrgA1- or MrgC11-specific agonists stimulated dose-dependent increases in intracellular free Ca2+ in a pertussis toxin-insensitive manner, but failed to alter basal or forskolin-stimulated levels of intracellular cAMP. Furthermore, studies using embryonic fibroblasts derived from various G{alpha} protein knockout mice demonstrated that both the MrgA1 and MrgC11 receptors are coupled to the G{alpha}q/11 signaling pathway. Screening of neuropeptides identified surrogate agonists, most of these peptides included a common C-terminal -RF(Y)G or -RF(Y) amide motif. Structure-function studies suggest that endogenous ligands of Mrg receptors are likely to be RF(Y)G and/or RF(Y) amide-related peptides and that postprocessing of these peptides may serve to determine Mrg receptor-ligand specificity. The differences in ligand specificity also suggest functional diversity amongst the Mrg receptors

Are Portable Imaging Intraoperative Radiographs Helpful for Assessing Adequate Acetabular Cup Positioning in Total Hip Arthroplasty?

Despite advances in surgical techniques and instrumentation, current intra-operative estimations of acetabular version in total hip arthroplasty are of limited accuracy. In the present study, two experienced orthopedic surgeons compared intra-operatively measured (using portable imaging) anteversions and vertical inclinations of acetabular components with those measured using standardized radiographs post-operatively in 40 patients. Of the all vertical inclinations measured from intra-operative radiographs, 72.5% (n=29) were within ±2°, and 97.5% (n=39) were within ±5° of those determined using post-operative radiographs, and for anteversion, 52.5% (n=21) were within ±2°, and 97.5% (n=39) were within ±5°. Post-operative radiographs demonstrated that 90.0% (n=36) of vertical inclinations and anteversions were within the adequate zone. Obviously, our method has its limitations, but the authors conclude that the method described in this article better allows surgeons to verify acetabular version intra-operatively. In particular, the described method is suitable in cases with a deformed acetabular anatomy and difficult revision surgery

Combined 18F-FDG PET/CT Imaging for the Initial Evaluation of Glottic Cancer

ObjectivesThe primary aim of this study was to determine whether 18F-FDG-PET/CT (PET/CT) scans provide additional diagnostic information in addition to the direct laryngoscopic examination (L/E) and contrast-enhanced CT (CT) in patients with glottic cancer during the initial evaluation.MethodsFifty-five consecutive patients with glottic cancer of the larynx that had L/E, CT and PET/CT were enrolled. The diagnostic value of each modality was compared for their accuracy in predicting the extent of the primary tumors on sub-site based analysis and the final tumor staging. The reference standards were either the surgical pathology findings or clinical/radiological follow-up outcome. Changes in patient care based on PET/CT results were compared with the treatment decisions based on L/E with CT.ResultsFor primary tumor sub-site based analysis, the sensitivity was significantly higher for L/E (92.8%) than for PET/CT (79.4%, P=0.028). The comparisons between L/E vs. CT and CT vs. PET/CT did not reach statistical significance. As an initial tumor-staging method the L/E had a diagnostic accuracy of 76.4%, compared to 61.8% for CT and 41.8% for PET/CT. The L/E and CT were better than the PET/CT (P=0.0009 and 0.049) for the initial TNM staging. PET/CT scanning changed the clinical decision-making based on the L/E with CT results in 12.7% of cases, of whom 5.5% had no additional PET/CT related benefit.ConclusionThe results of this study showed that PET/CT imaging added no clinical information benefit compared to the L/E and CT for the initial evaluation of patients with glottic cancer

A Rare Case of Aortic Valve Myxoma: Easy to Confuse With Papillary Fibroelastoma

Myxoma of the aortic valve is an exceedingly uncommon condition. In this article, we report the case of a 72-year-old man with myxoma arising from the aortic valve. We extirpated the mass and repaired the aortic valve with the patient under cardiopulmonary bypass. The postoperative course was uneventful. Histological examination confirmed that the mass was a myxoma

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice

Myung Joo Kang1, Jae Yoon Eum1, Mi Sook Jeong2, Sang Han Park1, Ki Young Moon1, Mean Hyung Kang1, Min Soo Kim1, Sun Eun Choi1, Min Won Lee1, Do Ik Lee1, Hyoweon Bang2, Chung Soo Lee2, Seong Soo Joo3, Kapsok Li2, Mi-Kyung Lee2, Seong Jun Seo2, Young Wook Choi11College of Pharmacy, ChungAng University, Heuksuk-dong, Dongjak-gu, Seoul, 2College of Medicine, Chung-Ang University, Heuksukdong, Dongjak-gu, Seoul, 3Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, South KoreaBackground: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).Methods: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.Results: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.Conclusion: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.Keywords: hirsutenone, elastic liposomes, atopic dermatitis, NC/Nga mice, Tat peptid

A Case of Non-Functioning Huge Adrenocortical Carcinoma Extending Into Inferior Vena Cava and Right Atrium

Primary adrenocortical carcinoma (ACC) is a rare tumor and its usual sites of metastasis are the lung (71%), lymph node (68%), liver (42%), and bone (26%). However, intracaval invasion extending into the right atrium is very rare and spontaneous regression of tumor burden in adrenal carcinoma is also rare. We report a case of ACC with direct invasion of the inferior vena cava and right atrium. A 34-yr-old male patient presented with progressive dyspnea, weight loss, and poor oral intake over 3 months. Non-functioning ACC with direct invasion of the inferior vena cava and right atrium was confirmed by imaging, pathologic, and hormonal study. Chemo-radio-therapy was attempted. However, tumor burden was not changed, but rather toxic hepatitis and thrombocytopenia were developed. His subjective symptoms and general conditions were improved after 1 month of conservative management and the patient was discharged. During clinical follow-up, this tumor showed spontaneous regression