Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase

Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.     

A Prospective Multicenter Trial of the Efficacy and Tolerability of Neoadjuvant Sunitinib for Inoperable Metastatic Renal Cell Carcinoma

This study aimed to evaluate the efficacy, safety, and tolerability of 2-cycled neoadjuvant sunitinib therapy (NST) in patients with inoperable metastatic renal cell carcinoma (mRCC). Between 2009 and 2012, 14 patients with inoperable mRCC from 5 Korean academic centers were prospectively enrolled after collecting their clinicopathological data and completing health-related questionnaires. The best overall response (BOR), safety profile, and changes in quality of life during NST were assessed using the RECIST criteria (version 1.0), CTCAE criteria (version 4.0), and the Cancer Quality of Life Questionnaire (QLQ-C30). Among the 14 patients, 9 patients (64.3%) experienced partial response or stable disease state, and 5 patients (35.7%) did not complete treatment, with 1 case of disease progression (7.1%), 3 grade 3 adverse events (21.4%), and 1 voluntary withdrawal (7.1%). Four patients (28.6%) were successfully converted to an operable state and underwent surgery after NST. The BOR for the primary renal lesions was 22.2%, with a median 1.3-cm diameter reduction (range: 0–2.8 cm) from a baseline diameter of 10.3 cm (range: 6.6–15.8 cm). The other 18 measurable metastatic lesions exhibited a BOR of 55.6%. The QLQ-C30 questionnaire results revealed significant improvements in the quality of life domain, although we observed significant increases in the scores for fatigue, nausea and vomiting, and the financial effects of NST (P < 0.05). Two-cycle NST provided limited efficacy for resectability of inoperable mRCC, despite mild improvements in the BOR of the primary lesion and quality of life (Clinical Trial Registry 1041140-1).     

Relationships of varicella zoster virus (VZV)-specific cell-mediated immunity and persistence of VZV DNA in saliva and the development of postherpetic neuralgia in patients with herpes zoster

There are no surrogate markers for the development of postherpetic neuralgia (PHN) in patients with herpes zoster (HZ). All patients with HZ were prospectively enrolled to evaluate the associations of saliva varicella zoster virus (VZV) DNA persistence and VZV-specific cell-mediated immunity (CMI) with the development of PHN. Slow clearers were defined if salivary VZV DNA persisted after day 15. Salivary VZV was detected in 60 (85.7%) of a total of 70 patients with HZ on initial presentation. Of 38 patients for whom follow-up saliva samples were available, 26 (68.4%) were classified as rapid clearers and 12 (31.6%) as slow cleares. Initial VZV-specific CMI was lower in slow clearers than rapid clearers (median 45 vs 158 spot forming cells/10 ⁶ cells, P = .02). Of the 70 patients with HZ, 22 (31.4%) eventually developed PHN. Multivariate analysis showed that slow clearers (OR, 15.7, P = .01) and lower initial VZV-specific CMI (OR, 13.8, P = .04) were independent predictors of the development of PHN, after adjustment for age and immunocompromised status. Initial low VZV CMI response and persistence of VZV DNA in saliva may be associated with the development of PHN.     

Craniofacial arteriovenous malformation: preoperative embolization with direct puncture and injection of n-butyl cyanoacrylate.

PURPOSE: To evaluate the use of n-butyl cyanoacrylate (NBCA) for preoperative embolization of craniofacial arteriovenous malformation. MATERIALS AND METHODS: Fourteen patients with craniofacial arteriovenous malformation (forehead [n = 9], deep facial [n = 3], occipital [n = 1], or lip [n = 1] lesion) were treated with injection of NBCA. Forehead lesions were supplied by ophthalmic (n = 6) and/or superficial temporal arteries (n = 7); and facial and scalp lesions, by bilateral internal maxillary (n = 4), facial (n = 2), and/or occipital arteries (n = 1). Lesions were percutaneously punctured with a 20-gauge needle in the area of arteriovenous connection. Direct angiography was performed before and after compression of venous drainage, and NBCA diluted 30%-50% with iodized oil was injected during venous compression. RESULTS: Postembolization arteriograms showed that six lesions were completely devascularized after single or multiple (one to nine) injections, and five were effectively devascularized (> or = 90%). Although three lesions were 60%-70% devascularized after injection, two of these were successfully extirpated with no notable blood loss. In nine patients, the ophthalmic arterial supply had disappeared after embolization. There were no procedure-related complications. CONCLUSION: Direct-puncture embolization with NBCA is an effective and safe technique for preoperative devascularization of craniofacial arteriovenous malformation. For safe and effective devascularization, compression of draining venous channels is thought to be important.     

Efficacy and Safety of Rebamipide versus Its New Formulation,AD-203, in Patients with Erosive Gastritis: A Randomized,Double-Blind,Active Control,Noninferiority, Multicenter,Phase 3 Study

Background/AimsThe mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta^Ⓡ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis.MethodsThis double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups AD-203 twice daily or Mucosta^Ⓡ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta^Ⓡ, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta^Ⓡ, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated.ResultsAccording to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta^Ⓡ-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta^Ⓡ-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta^Ⓡ-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates.ConclusionsThe new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta^Ⓡ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.     

Developing a Dementia Platform Databank Using Multiple Existing Cohorts

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging pre-existing dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson’s disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.