In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branchedchain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branchedchain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet.Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4 + T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GMCSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ + Th1 cells, IL-4 + Th2 cells, IL-9 + Th9 cells, IL-17 + Th17 cells, and Foxp3 + Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet.Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4 + T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GMCSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ + Th1 cells, IL-4 + Th2 cells, IL-9 + Th9 cells, IL-17 + Th17 cells, and Foxp3 + Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.2 ± 0.4 h and 1.4 ± 0.5 h, respectively; absolute bioavailability was calculated as 3.6%. Further, AChE activity was inhibited by increasing plasma concentrations of donepezil, and a maximum inhibition of 31.5 ± 5.7% was observed after donepezil treatment in hairless rats. Plasma AChE activity was negatively correlated with plasma donepezil concentration. The pharmacological effects of donepezil are dependent upon its concentration and AChE activity; therefore, we assessed the effects of donepezil on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg) significantly prevented the progression of scopolamine-induced memory impairment in mice. As the concentration of donepezil in the brain increased, the recovery of spontaneous alternations also improved; maximal improvement was observed at 46.5 ± 3.5 ng/g in the brain. In conclusion, our findings suggest that the AChE inhibitory activity and pharmacological effects of donepezil can be predicted by the concentration of donepezil. Further, 46.5 ± 3.5 ng/g donepezil is an efficacious target concentration in the brain for treating learning and memory impairment in rodents.
Acetylcholinesterase* ; Animals ; Biological Availability ; Brain ; Humans ; Learning* ; Memory* ; Mice ; Plasma ; Rats, Hairless ; Rodentia*

PURPOSE: Although several studies have attempted to identify a relationship between Peyronie's disease (PD) and associated comorbidites including diabetes mellitus (DM), little is known about the effect of DM on the natural history of PD. We investigated the clinical characteristics of PD patients with DM for understanding of this association. MATERIAL & METHODS: Patients with PD and DM (Group 1) and those with no DM (Group 2) were compared by age, duration of PD, size and location of the plaque, severity of the penile curvature, presence of pain on erection, and the severity of erectile dysfunction by IIEF-5 scores. RESULTS: There was no significant difference in mean age of patients, duration of PD and location of the plaque between Group 1 and Group 2, respectively. The rate of severe penile curvature (>60degrees) was more frequent in Group 1 (22.7% vs. 8.6%). Plaque size was significantly bigger in Group 1 than that of Group 2 (2.2+/-1.6 vs. 1.7+/-1.3 cm, p<0.05) and mean degree of penile curvature was significantly greater in Group 1 than Group 2 (31.4+/-8.7degrees vs. 24.9+/-6.6degrees, p<0.05). The rate of severe ED (IIEF-5 < or =11 score) was significantly greater in Group 1 (18.2% vs. 4.2%, p<0.05) but pain on erection was significantly greater in Group 2 (31.8% vs. 49.2%, p<0.05). CONCLUSIONS: These results suggest that the presence of DM in patients with PD exaggerates the severity of PD by affecting the size of the plaque, penile curvature and consequent erectile dysfunction.
Diabetes Mellitus ; Erectile Dysfunction ; Humans ; Male ; Natural History ; Penile Induration

Orthotopic bladder replacement using detubularized ileum has become a popular form of continent urinary diversion after performing radical cystectomy for treating invasive bladder cancer. Delayed spontaneous rupture of an orthotopic ileal bladder has rarely been reported in the English literature and it has never been reported in Korea. We describe here a case of delayed spontaneous rupture of an ileal orthotopic neobladder secondary to overdistension, and this was successfully managed nonoperatively.
Cystectomy ; Ileum ; Korea ; Rupture ; Rupture, Spontaneous* ; Urinary Bladder ; Urinary Bladder Neoplasms ; Urinary Diversion

Prostate cancer and male breast cancer are similar in many ways, including the potential role of steroidal hormones in their pathogenesis and shared genetic abnormalities. However, the combination of these cancers in the same patient is rare. Herein, the case of a male patient, diagnosed with synchronous prostate and breast cancers, is reported.
Breast Neoplasms* ; Breast Neoplasms, Male ; Breast* ; Diagnosis* ; Humans ; Male* ; Neoplasms, Multiple Primary ; Prostate* ; Prostatic Neoplasms

PURPOSE: When the bladder outlet is partially obstructed, The expression of iNOS and collagen type III is caused by ischemia of bladder. This study aimed to evaluate the hemodynamic changes and the expression of inducible nitric oxide synthase(iNOS) and collagen type III of bladder during acute stages of partial bladder outlet obstruction in female rats and conducted a research on the effect of alpha-adrenergic blocker. MATERIALS AND METHODS: Thirty mature Sprague-Dawley rats were randomly divided into three groups; 3 days(Group I), 7 days(Group II), 14 days(Group III), depending on the term of partial bladder outlet obstruction. After obstruction, each group was subdivided into the experimental groups and the control groups; terazosin(0.4 mg/kg) was administered to the experimental groups and normal saline was administered to the control groups for a week. The degree of expression of iNOS and collagen type III in bladder was investigated by immunohistochemical stain and Western blot. RESULTS: The blood flow of experimental groups showed significant increase compared to control groups(p<0.05). The expression of iNOS and collagen type III of exerimental groups was significantly decreased compared to the controls(p<0.05). CONCLUSION: This study suggests that alpha-adrenergic blocker makes increase in blood flows to bladder and may have a role of prevention from functional damage of bladder.
Animals ; Blotting, Western ; Collagen Type III ; Female ; Hemodynamics ; Humans ; Ischemia ; Nitric Oxide ; Rats* ; Rats, Sprague-Dawley ; Urinary Bladder Neck Obstruction ; Urinary Bladder*

PURPOSE: To present the short-term results of an extraperitoneal laparoscopic radical prostatectomy technique. MATERIALS AND METHODS: 18 patients underwent a laparoscopic radical prostatectomy for clinical stages ranging from cT2a to cT3b, as found on MR prostate imaging. RESULTS: Our extraperitoneal laparoscopic radical prostatectomy procedure was technically successful in all 18 patients. The mean age of the patients was 65.3 years. The mean surgical time was 421 minutes. The Foley catheter was able to be removed on postoperative days 10, 14 and 20 from 7, 5 and 3 patients, respectively, and from 1 on each of the 23, 30 and 34 postoperative days. The final pathological results were 2, 6, 5, and 5 stages pT2a, pT2b, pT3a and pT3b, respectively. There was a positive surgical margin in 8 patients (44.4%). CONCLUSIONS: Our initial series of extraperitoneal laparoscopic radical prostatectomies are presented. Using an extraperitoneal approach, avoiding the peritoneal cavity, can minimize the chances of the bowel coming into contact with electrocautery, and the associated potential sequelae. The extraperitoneal laparoscopic radical prostatectomy procedure is developmental; therefore, long-term data are currently unavailable. Nevertheless, this technique could potentially be an attractive addition to the available radical prostatectomy procedures.
Catheters ; Electrocoagulation ; Humans ; Laparoscopy ; Operative Time ; Peritoneal Cavity ; Prostate ; Prostatectomy*