Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea

Background@#Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group). @*Methods@#This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction. @*Results@#Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index. @*Conclusion@#There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

MiR-9 Controls Chemotactic Activity of Cord Blood CD34⁺ Cells by Repressing CXCR4 Expression

Improved approaches for promoting umbilical cord blood (CB) hematopoietic stem cell (HSC) homing are clinically important to enhance engraftment of CB-HSCs. Clinical transplantation of CB-HSCs is used to treat a wide range of disorders. However, an improved understanding of HSC chemotaxis is needed for facilitation of the engraftment process. We found that ectopic overexpression of miR-9 and antisense-miR-9 respectively down- and up-regulated C-X-C chemokine receptor type 4 (CXCR4) expression in CB-CD34⁺ cells as well as in 293T and TF-1 cell lines. Since CXCR4 is a specific receptor for the stromal cell derived factor-1 (SDF-1) chemotactic factor, we investigated whether sense miR-9 and antisense miR-9 influenced CXCR4-mediated chemotactic mobility of primary CB CD34⁺ cells and TF-1 cells. Ectopic overexpression of sense miR-9 and antisense miR-9 respectively down- and up-regulated SDF-1-mediated chemotactic cell mobility. To our knowledge, this study is the first to report that miR-9 may play a role in regulating CXCR4 expression and SDF-1-mediated chemotactic activity of CB CD34⁺ cells.

Analysis of Loss of Heterozygosity in Korean Patients with Keratoacanthoma

Loss of heterozygosity (LOH) has been established as an important genetic mechanism giving rise to malignant neoplasia. The mechanism of LOH has been shown to cause basal cell carcinoma and malignant melanoma as well as other types of skin cancer. A few studies on LOH in sporadic keratoacanthomas have been reported. The purpose of this study was to investigate the significance of LOH in the pathogenesis of sporadic keratoacanthomas developed in 10 Korean patients. The presents of LOH at 7 microsatellite markers (D2S286, D3S1317, D5S346, D9S160, D9S171, D10S185, and D17S261) were evaluated in sporadic keratoacanthomas. LOH was found in only 1 of 10 cases at D10S185. The low frequency of LOH detected in this study suggests that LOH may not be significant in the induction of sporadic keratoacanthomas.

Analysis of Microsatellite Instability and Loss of Heterozygosity in Sporadic Keratoacanthoma / 대한해부학회지

Tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC)and from a subset of patients with the related Muir-Torre syndrome exhibit a type of a genetic instability, known as microsatellite instability (MIS), which results from mutations that inactivate DNA mismatch repair genes. Keratoacanthomas resemble squamous cell carcinoma but after a period of rapid growth over a few months they involute completely. The detection of MIS in a keratoacanthoma from a patient with Muir-Torre syndrome suggested that defective mismatch repair genes may play a role in the pathogenesis of these neoplasmas. In order to elucidate the significance of both MIS and loss of heterozygosity (LOH)in the pathogenesis of sporadic keratoacanthomas, the presents of MIS and LOH at 11 microsatellite markers (D2S286, D2S367, D3S1317, D5S346, D9S16, D9S171, D10S89, D10S185, D11S904, D17S261, and D17S520) were evaluated in randomly selected sporadic keratoacanthomas. MIS and LOH were found only in 1 of 10 cases at D17S261 and D10S185, respectively. In conclusion, the low frequency of MIS and LOH detected in this study suggests that neither MIS nor LOH appear to be significant in the induction of sporadic keratoacanthomas.

Correction of Cryptotia Using Lotus Flower Shaped V-Y Advancement Flap and Auriculocephalic Sulcus Percutaneous Cinch Sutures

In cryptotia the upper part of the auricle is buried beneath the temporal scalp, so the upper auriculocephalic sulcus is absent and auricular cartilage deformity is accompanied. The goals of surgical correction of cryptotia are to release the upper ear from temporal scalp to restore auriculocephalic sulcus, and to correct the cartilage deformity. Authors have experienced 23 auricles in 14 patients with cryptotia to correct cryptotia using lotus flower shaped V-Y advancement flap for the upper auricular skin deficiency and scoring for cartilage deformity. Lotus flower shaped flap is designed above superior pole of auricle. Designed flap has wider lower third than conventional V-Y flap. After complete exposure of upper auricular cartilage, cartilage deformity is corrected by scorings on lateral surface of the scapha and medial surface of the superior crus of antihelix. For construction of auriculocephalic sulcus, the flap is advanced inferiorly about 1 cm and 3 stab incisions on the flap are made at the expected auriculocephalic sulcus. The cinch suture is done between dermal layer of the stab incisions and auriculocephalic sulcus cartilage with 4-0 Prolene . Packing gauze is tied at corrected scapha for contour maintenance. A satisfactory contour of scapha and antihelical crus and deep auriculocephalic sulcus were maintained postoperatively. However, hypertrophic scar formation was found due to tension. Our method is similar to Ono's method in triangular flap shape. But the lotus flower shaped flap has wider lower 1/3 than Ono's triangular flap and provides sufficient skin for formation of auriculocephalic sulcus without additional rhomboid flap elevation in front of the ear.

Analysis of Prognostic Factors and Outcome of Early Gastric Cancer with and without Lymph Node Metastasis

PURPOSE: Lymph node (LN) metastasis and depth of invasion are known to be prognostic factors in early gastric cancer (EGC). This study was designed to determine the clinicopathological features of EGC with and without LN metastasis and an appropriate procedure for EGC. METHODS: The authors retrospectively reviewed 489 patients with EGC who underwent curative resection with LN dissection between January 1990 and December 1997 at the Department of Surgery, Keimyung University Dong San Medical Center. The authors divided the 489 patients into two groups. Group 1: EGC with LN metastasis, Group 2: EGC without LN metastasis. We analyzed and compared the clinicopathologic features (age, sex, tumor location and size, gastric resection and LN dissection, macroscopic type, depth of invasion, histological type, Lauren classification and lymphatic and vascular invasion) of the two groups. RESULTS: The incidence of EGC among all gastric cancer was 29.1% and increased annually (19.1% in 1990, 31.5% in 1994 and 40.2% in 1997). The incidence of LN metastasis was 16.2% (79/489) with 7.2% in mucosal cancer and 26.7% in submucosal cancer. Univariate analysis of 12 prognostic factors revealed only 4 factors, that were statistically significant: depth of invasion, tumor size, histologic type and lymphatic invasion. Multivariate analysis of these 4 significant prognostic factors did not yield significant results but the risk ratio revealed depth of invasion, tumor size, histological type and lymphatic invasion occurred in order of decreasing frequency. The five-year survival rate of EGC was90.83% (91.82% in EGC with LN metastasis and 85.80% in EGC without LN metastasis, p=0.0242). The relationship between the depth of invasion, macroscopic type, tumor size and LN metastasis revealed there was no LN metastasis in tumors of less than 2.0 cm in size in the elevated type (both in mucosal and submucosal cancer) and less than 1.0 cm in the size in the depressed type (only in mucosal cancer). CONCLUSION: Gastrectomy without LN dissection can be applied for EGC less than 2.0 cm in size in elevated types (both in mucosal and submucosal cancer) and less than 1.0 cm in size in depressed types (only in mucosal cancer). Conventional gastrectomy with LN dissection is recommended in other early gastric cancer.

Simultaneous Correction of Unilateral Temporomandibular Joint Ankylosis and Mandibular Hypoplasia Using Combined Arthroplasty and Mandibular Distraction

Damage of temporomandibular joints in infancy may result in ankylosis and alteration of the mandibular growth. In case of unilateral ankylosis occurring in early childhood, a mandibular hypoplasia of the affected side usually follows. The patients have limitation of mouth opening, poor oral hygiene, facial and mandibular growth disturbances, and rarely, upper airway obstruction in the form of either night snoring or obstruction sleep apnea. The objective of this study is to show the use of distraction osteogenesis in mandibular hypoplasia associated with ankylosis and to present our technique for the treatment of mandibular hypoplasia with unilateral ankylosis in infancy consisting of simultaneous arthroplasty which treats the ankylosis and mandibular distraction and enables to correct the facial asymmetry in the same procedure. Between November 1999 and May 2000, three girl patients (42, 44, and 48 months old) who had mandibular hypoplasia associated with ankylosis were treated with simulatneous arthroplasty and distraction osteogenesis. Two kinds of arthroplasties, consisting of gap arthroplasty for one patient and interpositional arthroplasty using a temporal fascia turn-over flap for the other two patients, were executed and mandibular distraction in all three patients. Mouth-opening exercises began on the first day following the operation. Mandibular distraction began on the fifth day after the operation at a rate of 1 mm per day (0.5 mm twice a day) and continued to achieve a slight overcorrection of deviated chin. From the first day after the operation, an increase in the mouth opening was achieved. The average duration of distraction was 20 days. Average duration of consolidation was 6 weeks. Oral opening increased from 2 to 20 mm in case of the first patient, from 4 to 28 mm in the second patient, and from 5 to 24 mm in the third patient. The follow-up period was from 5 to 12 months (mean 8 months). At the time of final evaluation, oral opening and a more normal facial contour persist. It is believed that mandibular distraction combined with arthroplasty offers a new therapeutic option for the treatment of mandibular hypoplasia associated ankylosis, with minimal morbidity and complications.

The Effect of Alkylating Agent Cyclophosphamide on the Testis of Pubertal Rat / 대한비뇨기과학회지

We examined the effects of the cyclophosphamide on the testis of pubertal rats. The effects of drug on the pubertal testis were compared to the prepubertal and postpubertal experimental groups. The drug was administered intraperitoneally l00mg/kg weekly for 3 weeks and then two and four weeks later the experimental groups were sacrificed.Rats4,7 and 12weeks old were selected as the prepuberty, puberty and adult groups respectively.In the all experimental groups except the prepubertal group which was sacrificed at postinjection 2 weeks, the body weight was significantly decreased compared to the control group. In the pubertal and adult group the testis weights were decreased (puberty 0.94+/-0.07gm at 2 weeks, 1.48+/-0.03gm at 4 weeks, adulthood 1.52+/-0.07gm at 2 weeks, 1.76+/-0.06gm at 4 weeks) very significantly compared to that of the control group(puberty: 1.53+/-0.06 at 2 weeks, 1.7l+/-0.07gm at 4 weeks, adulthood: 1.83+/-0.08gm at 2 weeks, 1.99+/-0.07gm at 4 weeks, p<0.0l). The seminiferous tubular diameter of the puberty group was very significantly decreased (269+/-24um at 2 weeks, 275+/-21um at 4 weeks, p<0.01) and decreased significantly in the adult group( 278+/-20 m at 2 weeks, 289+/-18um at 4 weeks, p<0.05)compared to that of the control group(puberty 2 weeks 291+/-22um, 4 weeks 289+/-25um, adulthood 2 weeks 290+/-22um, 4 weeks 298+/-21um) Our results suggest that the prevention of testicular damage is needed in the anticancer chemotherapy of the reproductive age group because testicular damage is significant during pubertal age.

Clinical Observation of the Effect of Sacral Block with Phenol in Hyperreflexic Bladder Patient / 대한비뇨기과학회지

Percutaneous chemical neurolysis of sacral nerve with phenol was performed on 11 cases of hyperreflexic bladder to augment bladder capacity and to make intermittent clean catheterization more feasible. Urodynamic evaluations were done before and after chemical neurolysis. Followup ranged from 10 months to 16 months(mean 13 months). Mean bladder capacity increased significantly after chemical neurolysis ( from 157.5ml to 340ml). No significant changes in bowel or injection sites were noted. Continence was improved in 100%, with 7 patients remaining completely dry and voiding with intermittent self-catheterization. The long term results were necessary but we considered the chemolysis of sacral nerve was available modality for hyperreflexic bladder patients, who did not respond to anticholinergic medication, before decide the more aggressive alternatives, such as augmentation cystoplasty or urinary diversion.