Thymoglobulin Versus Basiliximab Induction Therapy in Low-Risk Kidney Transplant Recipients: A Single-Center Experience.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that T-cell-depleting agents should be used only for kidney transplant (KT) recipients at high immunologic risk. However, the effects of thymoglobulin induction therapy in low-immunologic risk KT recipients on tacrolimus, mycophenolic acid, and steroid have not been elucidated yet. METHODS: We retrospectively collected 6 months postoperative clinical data, for low-immunologic risk KT recipients at Soonchunhyang University Hospital. Recipients were divided into thymoglobulin and basiliximab groups, based on the induction agent used. Low-immunologic risk recipients were defined as those with panel-reactive antibody level <30% at the time of kidney transplantation. The incidence of biopsy-proven acute rejection and borderline change was compared between the two groups. RESULTS: Of the 46 low-immunologic risk patients, 25 received thymoglobulin. The incidence of biopsy-proven acute rejection was 0% (n = 0) and that of borderline change was 8% (n = 2) in the thymoglobulin group. The basiliximab group had a significantly higher incidence of rejection (23.8%; n = 5; P = .015) and borderline change (42.9%; n = 9; P = .006). No significant difference in estimated glomerular filtration rate was found between the two groups at 6 months after kidney transplantation. Cytomegalovirus (CMV) infection occurred more frequently in the thymoglobulin group than in the basiliximab group. All patients with CMV infection in both groups were effectively treated with pre-emptive intravenous ganciclovir therapy. CONCLUSIONS: In low-immunologic risk KT recipients who received tacrolimus, mycophenolic acid, and steroid therapy, thymoglobulin induction therapy significantly reduced the incidence of biopsy-proven acute rejection and borderline change compared with basiliximab induction therapy.

STAT3 activation in endothelial cells is important for tumor metastasis via increased cell adhesion molecule expression.

Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesion molecule expression. Collectively, our findings demonstrate that STAT3 activation in ECs promotes tumor metastasis through the induction of cell adhesion molecules, demonstrating a role for ECs in response to tumor cells during tumor metastasis.

Impact of opportunistic salpingectomy on anti-Müllerian hormone in patients undergoing laparoscopic hysterectomy: a multicentre randomised controlled trial.

OBJECTIVE: The aim of the study was to investigate whether opportunistic salpingectomy has any deleterious effects on ovarian reserve and increases surgical risk in patients undergoing laparoscopic hysterectomy. DESIGN: A multicentre, randomised controlled trial. SETTING: Three university hospitals in Korea. POPULATION: Sixty-eight patients undergoing laparoscopic hysterectomy for the treatment of symptomatic benign uterine diseases. METHODS: Patients were randomised to undergo either opportunistic salpingectomy (n = 34) or no salpingectomy (n = 34) during laparoscopic hysterectomy. MAIN OUTCOME MEASUREMENTS: The primary and secondary outcome measures were the change of ovarian reserve, determined by the rate of decline in anti-Müllerian hormone (AMH) level from before surgery to 3 months post-surgery and surgical outcomes, respectively. RESULTS: Baseline demographic and clinical characteristics were similar between the two groups. There was also no difference in operative outcomes such as operative time, operative bleeding, or complications between the two groups. In both groups, postoperative AMH levels were significantly lower than preoperative AMH levels (both, P < 0.01). The decline rate in AMH was 12.5% (interquartile range 0.8-60.9%) in the opportunistic salpingectomy group and 10.8% (interquartile range 6.9-27.4%) in the no salpingectomy group, with no significant difference between both groups (P = 0.898). CONCLUSIONS: Opportunistic salpingectomy at the time of laparoscopic hysterectomy did not have any negative effects on ovarian reserve or increased surgical risk. TWEETABLE ABSTRACT: Opportunistic salpingectomy did not have any negative effects on ovarian reserve or increased surgical risk.

Clinical assessment of rosacea severity: oriental score vs. quantitative assessment method with imaging and biomedical tools.

BACKGROUND: Rosacea is a common chronic inflammatory disorder affecting facial skin. Currently, no accurate and objective method is available for assessing the severity of rosacea. Most studies use the National Rosacea Society Standard (NRSS) grading method, which lacks objectivity and yields varying results. METHODS: Eighteen patients with rosacea were included. Clinical severity was assessed on the basis of the NRSS grade, Investigators' Global Assessment, Patients' Global Assessment, and Dermatology Quality of Life Index. A skin color analysis system was used to measure the facial area showing erythema, and biophysical parameters of facial skin (transepidermal water loss and skin surface hydration) were examined. To find statistical significant in classification severity of the rosacea, statistical analysis was performed with all parameters. RESULTS: A significant correlation (P < 0.05) was found between the NRSS grade, facial area showing erythema, and biophysical parameters. The latter two factors differed significantly among patients with rosacea of different levels of severity (mild, moderate, severe; P < 0.05). CONCLUSION: Color imaging systems can be useful and reliable for evaluating the severity of rosacea, in addition to biophysical parameter assessment. The combination of these two analytical methods enabled objective and quantitative evaluation of the severity of rosacea.

Prognostic value of negative interim 2-[¹8F]-fluoro-2-deoxy-d-glucose PET/CT in diffuse large B-cell lymphoma.

AIM: To assess the prognostic value of negative interim combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent (18)F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal (18)F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. RESULTS: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0-2; p<0.001). CONCLUSION: Despite a negative interim (18)F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score.

A phantom model study to identify the most effective manual aspiration thrombectomy for acute deep-vein thrombosis of the lower extremity.

AIM: To identify the most effective manual aspiration thrombectomy (MAT) method for the initial endovascular management of acute deep-vein thrombosis (DVT) in the lower extremity using a phantom model. MATERIALS AND METHODS: An acute DVT phantom model was created by infusing a bovine acute thrombus in a 20-mm diameter, 120-cm long plastic tube with banding of the distal portion. A total of 32 types of aspiration methods using combinations of two aspiration catheters (8 and 10 Fr), four syringes (10, 20, 40, and 50 ml), and four different aspiration methods (I, II, III, and IV) were performed. Each method was performed 10 times. The total weight of the aspirated thrombus was measured and compared among the 32 aspiration methods. The aspiration methods were classified based on the length of the dynamic catheter withdrawal (0 cm [method I], 15 cm [II], 30 cm [III], or >45 cm [IV]) while maintaining continuous negative pressure using a syringe. Analysis of variance and Student's t-test were used for statistical analysis. RESULTS: There were no statistically significant differences in the total amount of aspirated thrombus among the various types of aspiration catheters and syringes; however, different aspiration methods showed significantly different results. Acute thrombus was most effectively aspirated by method IV irrespective of the catheter and syringe used. The longer the length of dynamic catheter withdrawal, the greater the amount of total thrombi that could be aspirated, irrespective of the type of aspiration catheter and syringe used (IV > III > II > I; p<0.05). CONCLUSION: MAT can be performed most effectively using method IV. Effective MAT relies on the length of the dynamic catheter withdrawal while maintaining continuous negative pressure using a syringe in the initial endovascular management of acute DVT in the lower extremity.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Syntenin regulates TGF-ß1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-ß type I receptor internalization.

Syntenin, a tandem PDZ domain containing scaffold protein, functions as a positive regulator of cancer cell progression in several human cancers. We report here that syntenin positively regulates transforming growth factor (TGF)-ß1-mediated Smad activation and the epithelial-to-mesenchymal transition (EMT) by preventing caveolin-1-mediated internalization of TGF-ß type I receptor (TßRI). Knockdown of syntenin suppressed TGF-ß1-mediated cell migration, transcriptional responses and Smad2/3 activation in various types of cells; however, overexpression of syntenin facilitated TGF-ß1-mediated responses. In particular, syntenin knockdown abolished both the basal and TGF-ß1-mediated repression of E-cadherin expression, as well as induction of vimentin expression along with Snail and Slug upregulation; thus, blocking the TGF-ß1-induced EMT in A549 cells. In contrast, overexpression of syntenin exhibited the opposite effect. Knockdown of syntenin-induced ubiquitination and degradation of TßRI, but not TGF-ß type II receptor, leading to decreased TßRI expression at the plasma membrane. Syntenin associated with TßRI at its C-terminal domain and a syntenin mutant lacking C-terminal domain failed to increase TGF-ß1-induced responses. Biochemical analyzes revealed that syntenin inhibited the interaction between caveolin-1 and TßRI and knockdown of syntenin induced a massive internalization of TßRI and caveolin-1 from lipid rafts, indicating that syntenin may increase TGF-ß signaling by inhibiting caveolin-1-dependent internalization of TßRI. Moreover, a positive correlation between syntenin expression and phospho-Smad2 levels is observed in human lung tumors. Taken together, these findings demonstrate that syntenin may act as an important positive regulator of TGF-ß signaling by regulating caveolin-1-mediated internalization of TßRI; thus, providing a novel function for syntenin that is linked to cancer progression.

Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53.

Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.

Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25-35 neurotoxicity.

Sulfuretin, one of the major flavonoid glycosides found in the stem bark of Albizzia julibrissin and heartwood of Rhus verniciflua, is a known anti-oxidant. We previously demonstrated that sulfuretin inhibits neuronal death via reactive oxygen species (ROS)-dependent mechanisms in human SH-SY5Y cells, although other relevant mechanisms of action of this compound remain largely uncharacterized. As part of our ongoing exploration of the pharmacological actions of sulfuretin, we studied the neuroprotective effects of sulfuretin against amyloid beta (Aß)-induced neurotoxicity in human SH-SY5Y and primary hippocampal neuron cells and investigated the possible mechanisms involved. Specifically, we found in the present study that sulfuretin significantly attenuates the decrease in cell viability, release of lactate dehydrogenase, and accumulation of ROS associated with Aß25-35-induced neurotoxicity in neuronal cells. Furthermore, sulfuretin stimulated the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of phosphatidylinositol 3-kinases (PI3K)/Akt. We demonstrated that sulfuretin induces the expression of heme oxygenase-1 (HO-1), an anti-oxidant response gene. Notably, we found that the neuroprotective effects of sulfuretin were diminished by an Nrf2 small interfering RNA (siRNA), the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), as well as the PI3K/Akt inhibitor LY294002. Taken together, these results indicated that sulfuretin protects neuronal cells from Aß25-35-induced neurotoxicity through activation of Nrf/HO-1 and PI3K/Akt signaling pathways. Our results also indicate that sulfuretin-induced induction of Nrf2-dependent HO-1 expression via the PI3K/Akt signaling pathway has preventive and/or therapeutic potential for the management of Alzheimer's disease.

Childhood facial vitiligo: how intractable is it?

BACKGROUND: Following the recent elucidation of its pathogenic mechanisms involving reactive oxygen species, use of vitamins, folic acid and antioxidants as adjuvant therapy has been suggested. OBJECTIVE: To evaluate the long-term outcome of childhood facial vitiligo who were treated with nutritional education, vitamin E (α-tocopherol 100-400 IU/day), folic acid (1-2 mg/day) and multivitamin intake and antioxidant cosmetics as the mainstay of treatment as well as the conventional therapies including oral, topical and/or intralesional corticosteroid, topical macrolactam, Excimer laser and epidermal graft. METHODS: Medical data and photographs of 111 paediatric facial vitiligo patients who had been followed up for longer than 1 year from March 1, 2003 to June 30, 2013 were extracted from data warehouse of electric medical records. Photographic evaluation and final visual outcome assessment was performed. RESULT: By investigator's assessment, 9% of patients demonstrated no improvement regardless of treatment modality, whereas 91% showed improvement of lesions. Among the latter, 33.3% resulted in >75% improvement; 18% in 50%-75% improvement; 26.1% in 25%-50% improvement; and 13.5% in <25% improvement. In the final visual outcome assessment, 'Looking excellent' was seen in 42.3%; 'looking very good' in 30.6%; 'looking good' in 17.1%; 'looking fair' in 9.0%; and 'looking bad' in 0.9%. CONCLUSION: Although childhood facial vitiligo is quite refractory to treatment, the long-term outcome of this condition is not dismal with conventional vitiligo therapy along with basic nutritional therapeutic regimen.

A new therapeutic option for facial seborrhoeic dermatitis: indole-3-acetic acid photodynamic therapy.

BACKGROUND: Indole-3-acetic acid (IAA) is a newly introduced photosensitizer of photodynamic therapy (PDT) for acne, presenting sebum-reducing, anti-inflammatory and antimicrobial activity. OBJECTIVE: This study was designed to evaluate the efficacy and safety of IAA-PDT in the treatment of facial seborrhoeic dermatitis. METHOD: In this prospective, single-blinded, 6-week trial, 23 patients with facial seborrhoeic dermatitis were treated with IAA-PDT with green light (520 nm) three times with 1-week intervals. Patients were evaluated at baseline, week 1, 2, 3 and week 6 (3 weeks after last treatment). Efficacy was determined by Seborrhoeic dermatitis Area and Severity Index (SASI), patient's assessment of the symptoms (4-point scale of itchiness, burning, erythema, scale and tightness), sebum secretion rate (measured with Sebumeter(®)), Erythema Index (EI, measured with Mexameter(®)) and physician's photographic assessment. Safety was evaluated by questionnaire at each visit. RESULT: For the 22 subjects completing the trial, SASI and total symptom significantly improved at week 2, which lasted until week 6. Sebum excretion was significantly reduced at week 2 and stayed reduced until week 6. EI presented continuous reduction throughout the study. Photographic assessment showed significant improvement at each visit. The procedure was painless, and no adverse event was observed during and after the treatment. CONCLUSION: IAA-PDT is a safe and effective therapeutic option for facial seborrhoeic dermatitis.

Anatomical analysis of incidental left atrial diverticula in patients with suspected coronary artery disease using 64-channel multidetector CT.

AIM: To describe and evaluate anatomical characterizations of incidental left atrial (LA) diverticula in patients with suspected coronary artery disease using 64-channel multidetector computed tomography (MDCT). MATERIALS AND METHODS: From October 2008 to June 2009, 2059 patients with suspected coronary artery disease underwent electrocardiogram-gated 64-channel MDCT. Five hundred and thirty-two LA diverticula were identified in 377 patients (18.3%, male to female ratio: 216:161, mean age 59±10.89 years, range from 20 to 91 years). Two radiologists retrospectively analysed the number (single or multiple), size (diameter and length), shape (cystiform or tubiform), surface (smooth or irregular), and location (right or mid or left/upper or lower/lateral or posterior). If the length/diameter was <1.5, the diverticular shape was considered to be cystiform. RESULTS: Among 532 LA diverticula, single (270/532, 51.1%), cystiform (411/532, 77.3%), and smooth (332/532, 62.4%) diverticula were found. The right upper region (255/532, 47.9%) was the most common location, followed by the left lateral area (172/532, 32.3%). The average diameter was 4.7±2 mm (range from 1-19 mm), and the average length was 4.7±2.1 mm (range 1-13 mm). The average ratio of length to diameter was 1.15 (range 0.25-1.45). The average number of diverticula was 2±1.06 (range 1-5). CONCLUSION: Incidental LA diverticulum is not an uncommon finding in patients with suspected coronary artery disease. MDCT can provide anatomical details of LA diverticula. However, further studies are needed to determine their clinical significance.

Immunoreactivity and protein levels of olfactory marker protein and tyrosine hydroxylase are not changed in the dog main olfactory bulb during normal ageing.

The immunoreactivity and protein expression of olfactory marker protein (OMP) and tyrosine hydroxylase (TH) in the main olfactory bulb (MOB) of the dog during normal ageing was investigated. OMP immunolabelling was observed only in nerve bundles of the olfactory nerve (ONL) and glomerular layers (GL) and there was no OMP expression within cell bodies of any layer. TH immunolabelling was detected in all layers of the MOB except for the ONL. Most of the neurons expressing TH were distributed in the juxtaglomerular region and had a morphological appearance consistent with periglomerular, external tufted or superficial short axon cells. Dendrites of TH-immunoreactive neurons were closely apposed to OMP-immunoreactive nerve bundles within the glomeruli. There was no significant age-related loss of OMP and TH immunoreactivity and protein concentrations of these molecules were consistent in dogs of different ages. These results suggest that olfactory signal transduction to the GL via axons of olfactory receptor neurons remains unchanged during ageing in the dog.

Percutaneous aspiration thrombectomy for the treatment of acute lower extremity deep vein thrombosis: is thrombolysis needed?

AIM: To assess the technical feasibility and initial success of aspiration thrombectomy as a potential alternative to lytic therapy in initial endovascular management of acute lower extremity deep vein thrombosis (DVT). MATERIALS AND METHODS: From July 2004 to October 2007, a retrospective analysis of 27 patients (male:female 5:22; mean age 59 years) with acute iliofemoral or femoropopliteal DVT of less than 2 weeks was performed. All patients underwent sonography of the lower extremities, and 13 patients underwent computed tomography (CT) venography. All patients received an inferior vena cava (IVC) filter and were initially treated with aspiration thrombectomy using the pullback technique with or without basket thrombus fragmentation. If persistent stenotic portions (>50% luminal narrowing) were noted, balloon angioplasty or stent placement was performed. Successful recanalization was defined as successful restoration of antegrade flow in the treated vein with elimination of any underlying obstructive lesion. RESULTS: The mean procedure time was 65 min (range 40-100 min). Successful initial recanalization was achieved in 24 patients (88.9%) without complications. Urokinase was required for three patients (11.1%) due to a hard thrombus remaining in the iliac vein. Of the 27 patients, 23 had residual venous stenosis in the common iliac vein or external iliac vein. Therefore, balloon angioplasty (n=23) and stent placement (n=22) was performed. The remaining four patients were treated using only aspiration thrombectomy without angioplasty or stent placement. CONCLUSION: Aspiration thrombectomy without catheter-directed thrombolysis is a safe and effective treatment for acute DVT of the lower extremities, and minimizes the risk of haemorrhagic complications.

A case of right renal infarction and subcapsular hematoma that simultaneously developed after cardiac angiography.

Of the several complications known to develop after cardiac catheterization, simultaneous acute renal infarction and renal subcapsular hematoma is rare. Here, the authors report a case of acute renal infarction with subcapsular hematoma that developed 4 hours after cardiac catheterization.