Non-invasive longitudinal monitoring of angiogenesis in a murine full-thickness cutaneous wound healing model using high-resolution three-dimensional ultrasound imaging.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the longitudinal monitoring of angiogenesis in a murine full-thickness cutaneous wound healing model using high-resolution three-dimensional (3D) ultrasound imaging. METHODS: Two C57BL/6 mice were used. Two-dimensional (2D) ultrasound images with the Color Doppler mode were acquired at regular spatial intervals on day 9, 11, and 14 after wounding. 3D ultrasound images were processed by reconstructing the 2D ultrasound image sequences. The wounds were harvested on day 14 and serial sections were immunohistologically stained with an anti-CD31 antibody. RESULTS: 3D ultrasound imaging with the Color Doppler mode showed the distribution of microvascular growth on days 9, 11, and 14 after wounding (44.6%, 51.5%, and 27.3% in wound 1, 55.8%, 38.1%, and 35.1% in wound 2, 60.6%, 62.6%, and 63.1% in wound 3, and 15.8%, 42.0%, and 31.9% in wound 4, respectively). A correlation was observed between % vascularity measured by paired 2D ultrasound imaging with the Color Doppler mode and sections immunohistologically stained for the anti-CD31 antibody (r=0.927, 0.871, 0.717, and 0.913 for wounds 1, 2, 3, and 4, respectively. P<.01). CONCLUSION: These results indicate that high-resolution 3D ultrasound imaging is useful for longitudinally evaluating the distribution of microvascular growth over the course of healing.

Physiological and appearance characteristics of skin maceration in elderly women with incontinence.

OBJECTIVE: To identify the physiological and appearance characteristics of skin maceration caused by urine and/or faeces and determine their suitability as risk indicators for incontinence-associated dermatitis. METHOD: This cross-sectional, comparative study involved sixty-nine elderly women with urinary and/or faecal incontinence who provided informed consent to participate. Exclusion criteria included serious medical problems, acute illness and the presence of damaged skin on the buttocks. The physiological and appearance characteristics of macerated skin on the buttocks of the patients were examined. Stratum corneum and dermis hydration levels, transepidermal water loss and skin pH were used to assess skin condition. Skin morphology (sulcus cutis) was confirmed using images at x15 magnification. The erythema index and white index were used to evaluate colour in the macerated skin areas. RESULTS: Forty-four patients exhibited skin maceration. Stratum corneum and dermis hydration levels were significantly greater in the maceration group than in the non-maceration group, as were transepidermal water loss, skin pH and differences in sulcus cutis interval between the buttock of interest and the subumbilical region. Furthermore, differences in the erythema and white indices between these two regions were significantly higher and lower, respectively, in the maceration group than in the non-maceration group. CONCLUSION: To our knowledge, this is the first report to note that there are interesting changes not only in the epidermal layer but also in the dermis layer in patients with skin maceration. This finding confirmed that skin maceration caused by incontinence is a severe condition. Moreover, the erythema index was the best index for identifying skin maceration caused by incontinence, indicating that it can be used for precise and easy identification of the condition in clinical practice.

Structural changes in dermal collagen and oxidative stress levels in the skin of Japanese overweight males.

OBJECTIVE: It has been reported that obese people have poorly organized dermal collagen structure because of the degradation of collagen fibers, which is caused by an increase in oxidative stress levels associated with the hypertrophy of subcutaneous adipose cells. However, it is unclear whether an increase in oxidative stress levels caused by the accumulation of subcutaneous adipose tissue and a change in the dermal structure also occur in overweight and obese Japanese people. The objectives of this study are to identify structural changes that occur in the dermis and to measure the levels of oxidative stress in Japanese overweight males. METHODS: The overweight group included 43 Japanese male volunteers aged between 25 and 64 years and with a body mass index (BMI) of ≥25 and <30. The control group included 47 male volunteers aged between 22 and 64 years and with BMI of <25. The 20-MHz Dermascan C® ultrasound scanner with software for image analyses was used. Echogenicity of the upper and lower dermis was measured. The mRNA expression level of heme oxygenase-1 (HMOX1) in hair follicles was quantitatively analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and was used as a marker of oxidative stress. Ultrasonographic imaging and collection of hair follicles were performed at the same site on the thigh, abdomen, and upper arm. RESULTS: The HMOX1 mRNA expression level in the abdomen and thigh was significantly lower in the overweight group than in the control group. Moreover, the echogenicity of the upper dermis of the abdomen and the lower dermis of the abdomen and thigh was significantly lower in the overweight group than in the control group. CONCLUSION: We detected an increase in oxidative stress levels and a decrease in the density of dermal collagen at the same site on the thigh, abdomen, and upper arm of Japanese overweight males. These findings suggest the fragility of the dermis of Japanese overweight males, which might have been caused by the accumulation of subcutaneous adipose tissue.

Factors associated with silent cerebral microbleeds in hemodialysis patients.

BACKGROUND: The recent development of gradient-echo T2*-weighted magnetic resonance imaging (MRI) has enabled the highly accurate detection of prior cerebral microbleeds (CMBs), which might indicate a higher risk of future intracerebral hemorrhage (ICH) and be a marker of cerebral small-vessel disease in the general population. The present study investigated the clinical factors associated with the presence of CMBs in hemodialysis (HD) patients. METHODS: Cranial MRI, including T2*-weighted MRI, was performed on 179 HD patients without symptomatic cerebrovascular disease and 58 healthy control subjects, and we investigated the prevalence of CMBs and clinical factors associated with the presence of CMBs. We also investigated the relationship between CMBs and other cerebral small-vessel diseases. RESULTS: The prevalence of CMBs was significantly higher in the HD patients than in the healthy subjects (45 patients (25.1%) vs. none in the healthy controls (0%), p < 0.0001). Multiple logistic regression analysis showed that independent and significant factors associated with the presence of CMBs were age, systolic blood pressure, diastolic blood pressure and pulse pressure. Moreover, the presence of CMBs correlated significantly with the presence of lacunar infarcts, periventricular hyperintensity and deep and subcortical white matter hyperintensity. CONCLUSIONS: These findings indicated a high prevalence of CMBs among HD patients, and that older age and high blood pressure were strong factors associated with the presence of CMBs. Moreover, CMBs were closely associated with other cerebral small-vessel diseases.

The persistence of drug-induced fever by teicoplanin--a case report.

OBJECTIVE: It was reported that the drug-induced fever of teicoplanin tended to persist after cessation of treatment. It is considered that the long half-life of teicoplanin causes the phenomenon. However there was no detailed report regarding plasma concentration of teicoplanin during onset of drug induced-fever. Therefore we investigated the relation between persistence of drug-induced fever and plasma concentration of teicoplanin. CASE: A 38-year-old male patient on the Left Ventricular Assist System (LVAS) was treated with teicoplanin for methicillin-resistant Staphylococcus aureus (MRSA) and he experienced drug-induced fever. Plasma concentrations of teicoplanin were measured not only during the treatment with the drug but also after it was discontinued. As such, plasma concentration was measured even when the fever had subsided. RESULTS: On Day 9 of treatment, the dose was increased from 400 to 600 mg, but the patient had a fever of about 38 - 39 °C. When the treatment was discontinued, it took 9 days for the fever to subside to a temperature of about 37 °C. The half-life of elimination of teicoplanin in the elimination phase is about 108 h, which is long. The fever persisted until the plasma concentration decreased to below 10 µg/ml, which is the effective trough concentration, and subsided when the estimated blood concentration was 7.5 µg/ml. CONCLUSIONS: We suggest that there is the possibility that the drug-induced fever due to teicoplanin persisted until the plasma concentration had decreased adequately. Close monitoring of plasma concentration is necessary, particularly when teicoplanin clearance is decreased such as in patients with renal dysfunction.

Use of ultrasound in assessment of necrotic tissue in pressure ulcers with adjacent undermining.

OBJECTIVE: To reveal the specific ultrasonic imaging findings of non-visible necrotic tissue in pressure ulcers (PUs) with undermining and describe the images objectively. The predictive validity of the specific images of the undermined necrotic tissue was also determined. METHOD: Using digital ultrasonography (12 MHz linear transducer, MyLab25; Hitachi Medical Corporation), we imaged PUs with undermining every 2 weeks. PUs were also monitored by DESIGN-R, a PU assessment tool, at the same time. RESULTS: Ten patients had 11 PUs with undermining and all ulcers were located in the sacral region. The necrotic tissue showed high echogenicity with no layers, unclear borders and an uneven gray level (cloud-like image). Granulation tissue appeared as a low echoic image which had no layers, was of coarse resolution and an even gray level. There were significant differences between the pixel uniformity of the necrotic tissue (84.0) and granulation tissue (53.9) compared with uninjured tissue (65.5; p=0.000 and 0.005, respectively). The sensitivity, specificity, and positive and negative predictive values of cloud-like image were 87.5%, 91.7%, 77.8% and 95.6%, respectively. CONCLUSION: The results suggest that cloud-like image is the most useful diagnostic indicator for non-visible necrotic tissue in PUs with undermining and is the best prognostic indicator for PU healing. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare. There were no external sources of funding for this study.

NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation.

BACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells.

Increasing the number of steps walked each day improves physical fitness in Japanese community-dwelling adults.

We aimed to investigate the effects of increasing the number of steps each day on physical fitness, and the change in physical fitness according to the angiotensin-converting enzyme (ACE) genotype. A total of 174 participants were randomly assigned to two groups. Subjects in group A were instructed for 24-week trial to increase the number of steps walked each day, while subjects in group B were instructed to engage in brisk walking, at a target heart rate, for 20 min or more a day on two or more days a week. The values of the 3-min shuttle stamina walk test (SSWT) and the 30-s chair-stand test (CS-30) significantly increased, but no differences in increase were found between the groups. A significant relationship was found between the percentage increase in SSWT values and the increase in the number of steps walked by 1 500 steps or more per day over their baseline values. Our results suggest that increasing the number of steps walked daily improves physical fitness. No significant relationships were observed between the change in physical fitness and ACE genotypes.

The role of cysteinyl-LT(1)receptor (CysLT(1)R) in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Renal I/R injury, a clinically important problem, is an invariable consequence of renal transplantation. The problem begins at the onset of acute tubular necrosis (ATN), when the transplantation includes a long ischemic interval or by use of a cardiac arrest donor's kidney. The cysteinyl leukotriene-1 (CysLT(1)), a potent lipid mediator in allergic disease, acts through the CysLT(1)R receptor. We researched the expression of CysLT(1)R in rat renal I/R injury as well as correlations with the degree of ATN. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia; rats were sacrificed at 0, 3, 5, 12, and 24 hours after reperfusion. CysLT(1)R expression was analyzed by immunohistochemistry. CysLT(1)R expression was observed only in endothelial cells of a normal kidney. CysLT(1)R expression was most intense on endothelial cells at 3 hours after reperfusion, and CysLT(1)R expression on endothelial cells gradually became weaker. Twelve hours after reperfusion, ATN extended throughout the ischemic kidney. Renal I/R injury gradually progressed at time after reperfusion. Several hours after the maximal CysLT(1)R expression, we observed the maximum renal I/R injury.

Strategies for maximizing heart and lung transplantation opportunities in Japan.

INTRODUCTION: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors. METHOD: Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function. RESULTS: Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requiring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%. CONCLUSION: Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.

Study of cysteinyl leukotriene-1 receptor in rat renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is a major cause of renal transplant dysfunction. Recent studies of I/R injury have focused on the function of neutrophils, the mechanisms of action of inflammatory cytokines, and oxygen free radicals, as well as other mediators. However, few reports address the cysteinyl leukotriene-1 receptor (CysLT1R), an important mediator of bronchial asthma in human beings. We examined the expression of CysLT1R in rat renal I/R injury. At laparotomy, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 minutes of ischemia, and the rats were killed after 0, 3, 5, 12, or 24 hours. Expression of CysLT1R analyzed at immunohistochemistry was observed only in endothelial cells in nonischemic kidney. At 0 to 3 hours after reperfusion, CysLT1R expression on endothelial cells gradually became stronger, being most intense at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney; nearly all of the tubular epithelial cells were destroyed. At 3 to 12 hours after reperfusion, CysLT1R expression gradually became weaker on endothelial cells. At 24 hours after reperfusion, CysLT1R expression was almost at the level of that in nonischemic kidney. Expression of CysLT1R was noted in a rat model of renal I/R injury. Several hours after the maximal CysLT1R expression, we observed the maximum renal I/R injury. These results may suggest a relationship between the CysLT1R and renal I/R injury.

A novel approach to successful ABO-incompatible high-titer renal transplantation.

BACKGROUND: Currently the long-term outcome among recipients of ABO-incompatible renal transplantations is excellent in Japan. However, previous reports have documented poor outcomes in patients with high (> 1:256) anti-A/B antibody titers pretreatment. The immunosuppressive protocol for ABO-incompatible high-titer renal transplantation has remained a medical challenge. METHODS: We treated 3 patients with high (> 1:512) anti-A/B antibody titers prior to ABO-incompatible renal transplantation. Our immunosuppressive protocol was initiated 1 month prior to surgery and included mycophenolate mofetil (1 g/d) and low-dose steroid (methylprednisolone [8 mg/d]). Two doses of the anti-CD20 antibody rituximab, (150 mg/m2) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6 to 8 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation combined with 2 doses of basiliximab. RESULT: With this protocol, the anti-A/B antibody was reduced to below 1:16 in all cases. All 3 patients underwent successful transplantation with a mean current serum creatinine of 1.32 mg/dL (range, 1.22-1.50 mg/dL). There were no episodes of antibody-mediated rejection. No serious complications or side effects were encountered. CONCLUSIONS: A preconditioning protocol consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression enabled ABO-incompatible renal transplantation in patients with high (> 1:512) anti-A/B antibody titer.

Experience of Lymphangiography as a Therapeutic Tool for Lymphatic Leakage After Kidney Transplantation.

INTRODUCTION: Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS: Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS: Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS: Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.

Activation of granulocytes by direct interaction with dendritic cells.

Granulocytes from human peripheral blood were co-cultured with conventional dendritic cells (cDC) or plasmacytoid DCs (pDC) to examine the effects of DCs on the activation or function of granulocytes. After co-culture of granulocytes with DCs, expression of the activation markers of granulocytes (CD63 and CD64) was up-regulated, and increased expression of CD50, the activation marker and ligand for CD209 (DC-SIGN) was also observed. The interaction of granulocytes with DCs was visualized as the cluster where DCs, especially cDCs, were surrounded by granulocytes to form a 'rosette'. After co-culture of granulocytes with cDCs, the secretion of elastase from granulocytes was enhanced significantly when examined cytohistochemically and by enzyme-linked immunosorbent assay. An increase in myeloperoxidase (another activation index of granulocytes) was also observed after co-culture with DCs. These findings suggest the functional and phenotypical activation of granulocytes by interaction with DCs. Furthermore, we examined the involvement of adhesion molecules in the granulocyte-DC interaction, and found that CD209 participates to some extent in this interaction.

Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 case reports.

OBJECTIVE: The purpose of the study was to demonstrate how the interaction between phenytoin and tacrolimus (FK 506) can be managed clinically and to characterize the change in FK 506 levels after discontinuation of phenytoin in two Japanese heart transplant recipients with different dosing periods ofphenytoin. METHODS: A drug interaction between phenytoin and FK 506 was investigated in 2 patients. The concentration-dose ratios (CDR: trough blood FK 506 level (ng/ml)/FK 506 dose (mg/day) on the previous day) were calculated as an index of the induction of the CYP3A4 enzyme during and after phenytoin therapy. RESULTS: About 2- to 3-fold dosages of FK 506 were required to maintain the required blood level when phenytoin was used concomitantly in the two cases examined. The FK 506 dose was constant within 21 days after discontinuing phenytoin in Patient 1 who had 36 days of phenytoin therapy. In Patient 2 with 21-day phenytoin therapy, the FK 506 doses and CDR varied for 10 days after discontinuing phenytoin, and expected FK 506 C0 levels were achieved within 11 days. CONCLUSIONS: The persistence of CYP induction after discontinuing phenytoin is dependent on the history of administration and, perhaps, on the dosing period in particular.

[Complications and problems of acute care in patients undergoing heart transplantation].

We have experienced 20 cases of heart transplantation at the National Cardiovascular Center. We are discussing postoperative complications and intensive care for those cases. Hemodynamic problems may be summarized as the denervated heart, transient cardiac dysfunction, pulmonary hypertension in the recipient's pulmonary circulation, and donor-recipient size mismatch. In a case with donor-recipient size mismatch, cardiogenic pulmonary edema developed immediately after the tracheal extubation, probably due to wound pain and afterload mismatch. In all patients, weaning from mechanical ventilation was smooth. Prolonged mechanical ventilation seemed to result from a delay in awakening, hemodynamic instability, lactic acidosis, and donor-recipient size mismatch. Acute renal insufficiency occurred in 8 patients, while 1 patient needed 12 hours of continuous hemodiafiltration. All of the patients received infusions atrial natriuretic peptide and restored renal insufficiency.

[Posttransplant complications in cardiac transplant recipients at National Cardiovascular Center].

UNLABELLED: We have performed 21 cases of heart transplantation at our institution. We retrospectively reviewed the complications and its incidence in those post transplant course. METHODS: Twenty-one heart transplant recipients (aged at transplant 14 to 61 year old, 16 male and 5 female, observation period: 4 to 99 months) were retrospectively reviewed. Transplant coronary artery disease (TxCAD) was defined as existence of severer than Stanford class IV maximum intimal thickness seen by intra-coronary ultrasound at their annual evaluation. The incidence of hypertension, diabetes, hyperlipidemia, renal dysfunction and malignancy were also reviewed. RESULT: One patient died after 4.3 year posttransplant due to systemic infections. Eight patients (38.1%) developed TxCAD, 4 patients (19%) developed hypertension, 2 patients (9.5%) developed diabetes, 1 patient (4.8%) developed hyperlipidemia. Renal insufficiency defined as serum creatinine level of greater than 1.5 mg/dl was seen in 2 patients (9.5%), however none of them showed severe renal dysfunction such as serum creatinine level of greater than 2.0 mg/dl or requiring dialysis. No malignancy was seen in our patients. Cellular rejection episodes requiring admission for treatment were seen in 3.1% of all biopsies performed. CONCLUSIONS: Survival rate of our cardiac transplant recipients was 95.2% at 8.3 years. TxCADs and renal insufficiency were seen in 38% and 9.5% of our patients respectively, however the incidences of these complications were lower than those in ISHLT 2006 registry. Even in Japan, long-term survivors after cardiac transplantation are increasing. Maintenance of not only the cardiac function but also other organ function is required in post transplant care.

Beneficial Effects of High-Dose Mizoribine on ABO-Incompatible Living-Related Kidney Transplantation: Two-Year Results by a Japanese Multicenter Study.

BACKGROUND: Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study. METHODS: A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0-9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8-10 ng/mL (C0), 100 ng-h/mL (AUC 0-9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100-200 mg/body) was administrated on day -14 and day -7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 µg/mL. RESULTS: Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively. CONCLUSIONS: A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.

Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription.

Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.