Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1β- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD⁺-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.
Adipokines ; Alveolar Bone Loss ; Animals ; Fibroblasts* ; Gene Expression* ; Gingiva ; Humans ; Inflammation ; Mice ; Niacinamide ; Nicotinamide Phosphoribosyltransferase ; Periodontal Diseases ; Periodontitis* ; Phenotype ; Up-Regulation

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) has been reported in HBV surface antigen (HBsAg)-positive patients undergoing chemotherapy, as well as HBsAg-negative patients with antibodies against HBV core antigen (HBcAg) and/or HBsAg (HBsAb). Chemotherapy-including rituximab-has recently been identified as a predictive factor for HBV reactivation in HBsAg-negative patients with malignant lymphoma. The aim of our study was to identify the factors predictive of HBV reactivation after chemotherapy in patients with malignant lymphoma. METHODS: We conducted a retrospective analysis of medical records from patients diagnosed with malignant lymphoma at Gachon University Gil Medical Center in City, County from January 2005 to December 2010. We subsequently determined HBsAg, HBsAb and anti-HBc status in the 196 patients treated with chemotherapy. RESULTS: The mean age of the patients was 57.3 +/- 14.5 years; 56.3% were male. A total of 172 of 196 (88%) patients in the study population were HBsAg (+) prior to chemotherapy. Three patients (3/11, 27.3%) in the HBsAg (+) group had confirmed HBV reactivation after chemotherapy. In addition, 26 of 196 (13%) patients in the study population tested HBcAg (+) positive prior to chemotherapy. One patient (1/15, 6.7%) in the HBsAg (-)/HBcAb (+) group had confirmed HBV reactivation. In the four patients with HBV reactivation, infection was resolved after treatment with 0.5 mg entecavir or 100 mg lamivudine. CONCLUSIONS: Reactivation of HBV after systemic chemotherapy can occur in HBsAg (-) patients. We recommend that malignant lymphoma patients undergoing chemotherapy be screened for HBV infection status, including HBcAg, and followed closely to prevent HBV reactivation.
Antibodies ; Antigens, Surface ; Drug Therapy* ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Lamivudine ; Lymphoma* ; Male ; Medical Records ; Retrospective Studies

BACKGROUND/AIMS: Encapsulating peritoneal sclerosis (EPS) is an often-fatal complication of long-term peritoneal dialysis (PD). We here report the clinical features of EPS in Korean PD patients from a single university center. METHODS: The data were collected retrospectively from 606 PD patients at Kyungpook National University Hospital, between August 2001 and August 2011. The diagnosis of EPS was based on clinical signs and symptoms, and confirmed by radiological findings. RESULTS: Eight patients (1.3%, four males) were diagnosed with EPS. The mean age of the patients was 48.5 years (range, 33 to 65). The mean duration of PD was 111.8 months (range, 23 to 186). All patients except for one had three or more episodes of peritonitis. Seven patients were diagnosed with EPS after stopping PD, and only one stayed on PD after initial diagnosis and treatment. Total parenteral nutrition and corticosteroids, in addition to tamoxifen therapy, were used to treat most of the patients, and one patient underwent surgery (adhesiolysis). The overall mortality rate was 50%. CONCLUSIONS: EPS is a serious, life-threatening complication in patients on long-term PD. To reduce the incidence and mortality rate of EPS, careful monitoring and early diagnosis is needed.
Adrenal Cortex Hormones/therapeutic use ; Adult ; Aged ; Female ; *Hospitals, University ; Humans ; Male ; Middle Aged ; Parenteral Nutrition, Total ; Peritoneal Dialysis/*adverse effects/mortality ; *Peritoneal Fibrosis/diagnosis/etiology/mortality/therapy ; *Peritonitis/diagnosis/etiology/mortality/therapy ; Republic of Korea ; Retrospective Studies ; Tamoxifen/therapeutic use ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome

PURPOSE: Macrophage migration inhibitory factor (MIF) may serve as a general marker for systemic inflammation in septic and nonseptic acute critical illness. Additionally, our previous experiment has demonstrated that immunosuppressant Prostaglandin E2 (PGE2) lowered MIF levels and inhibited T-cells proliferation when compared to control levels. The addition of hypertonic saline (HTS) increased MIF production as compared with PGE2-stimulated T-cells in concordance with restore PGE2-suppressed T-cells proliferation. Generally, HTS has been well known for its anti-inflammatory effect so far. Therefore, the experiments were conducted to evaluate MIF after stimulating lipopolysaccharide (LPS) either in the presence or absence of HTS in monocyte, in response to early phase injury. METHODS: Human acute monocytic leukemic cell line (THP-1) cells were cultured in RPMI media, to a final concentration of 1 x 10(6) cells/mL. The effect of HTS on LPS-induced MIF was evaluated in monocyte with 1 microg/mL LPS. HTS at 10, 20 or 40 mmol/L above isotonicity was added. MIF concentrations of the supernatant were determined by enzyme-linked immunosorbent assay, and cell lysates were used for Western blots analysis to determine the MIF expression. RESULTS: MIF concentrations in the cell supernatant increased in LPS-induced cells compared to control cells. Also, levels of MIF protein expression were higher in LPS stimulating cells. However, the addition of HTS to LPS stimulated cell restored MIF concentrations and MIF expression. CONCLUSION: The role of HTS in maintaining physiological balance in human beings, at least in part, should be mediated through the MIF pathway.
Anti-Inflammatory Agents ; Blotting, Western ; Cell Line ; Critical Illness ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunosuppression ; Inflammation ; Lipopolysaccharides ; Macrophage Migration-Inhibitory Factors ; Macrophages ; Monocytes ; Saline Solution, Hypertonic ; T-Lymphocytes

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Limy bile is a rare condition characterized by excessive precipitation of calcium carbonate in the gallbladder; limy bile in the common bile duct is also very rare. Limy bile was first described by Churchman in 1911. The etiology of limy bile is unclear, but complete cystic duct obstruction by gallstones is believed to be a prerequisite for the development of limy bile. Recently, we experienced a case with obstructive jaundice in which the initial simple radiograph showed limy bile in the cystic and common bile ducts, but not the gallbladder. Here, we report the case and review the literature.
Bile ; Calcium Carbonate ; Common Bile Duct ; Cystic Duct ; Gallbladder ; Gallstones ; Jaundice, Obstructive

PURPOSE: To report a rare case of primary mucinous adenocarcinoma arising from a sweat gland in the eyelid. CASE SUMMARY: A 68-year-old male presented to our hospital with a painless, superficial nodular lesion over the skin of the right lateral canthus that had slowly grown over the past two years. The patient had a history of surgical excision for three nodular lesions at the same site 5 years ago, and an excisional biopsy was mucinous adenocarcinoma with a positive margin. A systemic evaluation, including whole-body Positron Emission Tomography scan (PET), chest computerized tomography, gastrointestinal endoscopy, and colonoscopy, revealed no other abnormal lesions. Therefore, the eyelid lesion was considered a primary mucinous adenocarcinoma of the skin. CONCLUSIONS: Primary mucinous adenocarcinoma of the eyelid can rarely metastasize. Therefore, a systemic examination is warranted to discriminate primary and metastatic adenocarcinoma and also to monitor the long-term follow-up for the evaluation of local recurrence.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Aged ; Biopsy ; Colonoscopy ; Endoscopy, Gastrointestinal ; Eyelids ; Humans ; Male ; Mucins ; Organothiophosphorus Compounds ; Positron-Emission Tomography ; Recurrence ; Skin ; Sweat Glands ; Thorax