AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

Associations between Sympathetic Activity, Plasma Concentrations of Renin, Aldosterone, and Parathyroid Hormone, and the Degree of Intractability of Blood Pressure Control in Hemodialysis Patients

This study was designed to examine how such factors as hemodialysis parameters, body mass index, renin and aldosterone concentrations, sympathetic nervous activity, and parathyroid hormone concentrations are associated with the control of hypertension in hemodialysis patients. Hemodialysis patients (n=114) were grouped into four categories. Group 1 had normal BP without antihypertensive medication. Group 2 needed one antihypertensive drug, Group 3 needed combination of two or three categories of antihypertensive drugs without minoxidil. Group 4 needed more than three categories of antihypertensive drugs including minoxidil. Parathyroid hormone, β2-microglobulin, renin and aldosterone, epinephrine, norepinephrine, and hemodialysis parameters were measured. The fractional clearance of urea as Kt/V urea was significantly lower in Group 3 and Group 4 than in Group 2 (p<0.01). Concentrations of parathyroid hormone were significantly higher in Group 4 than the other groups (p<0.01). Pre-hemodialysis norepinephrine concentrations were significantly higher in Group 4 than the other groups (p<0.05). Traditional factors associated with hypertension did not seem to be relevant to the degree of hypertension in hemodialysis patients in the present study. In conclusion, poor Kt/V urea, elevated parathyroid hormone concentrations, and elevated concentrations of plasma norepinephrine seemed to be the factors that might be associated with control of hypertension in hemodialysis patients

Stability and safety of transbronchial dye mixture for preoperative localization in a porcine model

Abstract Objective For thoracoscopy, the usefulness of a dye mixture of indigo carmine and Lipiodol for localizing lung lesions has been reported. However, little is known about the stability and safety of this dye mixture injected on the visceral pleura through a bronchoscope. Methods Porcine models were divided into three groups according to the detection time of the dye mixture: group A with a detection time of 4 h; group B, 8 h; and group C, 24 h. A dye mixture of indigo carmine and Lipiodol (0.5 mL each) was sprayed onto the visceral pleura both in the ventral and dorsal regions via a spray catheter. Results Twelve markings were created on the visceral pleura of the porcine lung (six ventral and six dorsal) in the six porcine models. At predetermined detection times, all 12 dye markings (100%) were visible on the visceral pleura. The mean longest diameter of the dye marking in the ventral and dorsal regions was 18.8 mm and 24.3 mm, respectively. In groups B and C, pathological changes in the lymphatic system, such as lymphatic dilatations, were found; minimal changes were found in group B, however, these changes with oval‐shaped lymphatic cysts and Lipiodol accumulation, were more evident in group C. Conclusions The dye mixture of indigo carmine and Lipiodol had reliable stability and visibility. In terms of safety, it may be necessary to check the dye mixture on the lung surface within 8 h

The usefulness of dynamic MRI for selection of surgical decompression levels in cervical OPLL

OAIID:RECH_ACHV_DSTSH_NO:A201701190RECH_ACHV_FG:RR00200003ADJUST_YN:EMP_ID:A079510CITE_RATE:DEPT_NM:의학과EMAIL:[email protected]_YN:CONFIRM:

Efficacy and Safety of Maca (Lepidium meyenii ) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Purpose: To evaluated the efficacy and safety of gelatinized Maca (Lepidium meyenii) for eugonadal patients with late onset hypogonadism symptoms (LOH). Materials and Methods: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males’ Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment. Results: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group. Conclusions: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03)

PURPOSE: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient&apos;s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. RESULTS: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2-positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). CONCLUSION: This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.Y

AKAP12 is highly expressed in the fibrotic scar surrounding the lesion in the process of CNS repair.

<p>(A) Brain sections were stained with antibody against AKAP12. AKAP12 was highly expressed in the normal meninges, and the number of AKAP12-positive cells in the scar tissue increased over time. Yellow boxes were magnified in right panels. Scale bar: 500 µm (large panels), 50 µm (magnified panels) (B) The AKAP12-positive area of three representative sections per mouse was analyzed using Image J. (Mean ± S.D.; n = 4 mice per each time; P*<0.05, P#<0.001) (C) Mouse brains were harvested at 21 days after photothrombotic injury. Brain sections were stained with antibody against AKAP12, GFAP (a marker for the glial scar) and fibronectin (a marker for the fibrotic scar). Yellow box was magnified in lower panels. Scale bar: 500 µm (largest panel), 200 µm (magnified panels) (D) AKAP12 gene KO was confirmed through genomic PCR and tissue western blotting. PCR analysis of mouse brain DNA showing the AKAP12 WT and KO alleles in the WT or AKAP12 KO mice and immunoblotting analysis of the brain lysates from the WT and KO mice using two different AKAP12 antibodies. (E) Mouse brains were harvested at 21 days after photothrombotic injury. The specificity of the AKAP12 signal was supported by lack of AKAP12 staining in the fibrotic scar in the AKAP12 KO mice. Scale bar: 200 um [LC: lesion core, FS: fibrotic scar, GS: glial scar].</p