Callyazepin (1) and (3R)-methylazacyclodecane (2), nitrogenous macrocycles, were isolated from a tropical Callyspongia sp. sponge. The combined spectroscopic analyses revealed that the structure of 1 ...is a bicyclic azepane ammonium salt of a novel structural class derived from mixed biogenetic origins. The configuration of the whole molecule and the conformation of the formamide group were assigned by proton-proton coupling constants, a NOESY analysis, and the application of the phenylglycine methyl ester method. The structure of 2 was identified using combined spectroscopic analyses and ECD measurements. These compounds exhibited moderate cytotoxic activities against the K562 and A549 cell lines.
Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other ...blood cells in the bone marrow, lymph nodes, and the spleen. Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.
Meroterpenoids from a Tropical Dysidea sp. Sponge Kim, Chang-Kwon; Woo, Jung-Kyun; Kim, Seong-Hwan ...
Journal of natural products (Washington, D.C.),
11/2015, Letnik:
78, Številka:
11
Journal Article
Recenzirano
Six new meroterpenoids (1-6), along with arenarol (7), a known rearranged drimane sesquiterpene hydroquinone, were isolated from a Dysidea sp. sponge collected from the Federated States of ...Micronesia. On the basis of the results of combined spectroscopic analysis, compound 1 was determined to be the cyclic ether derivative of 7, whereas 2 and 3 were assigned as the corresponding sesquiterpene quinones containing taurine-derived substituents. Compounds 4-6 possess a novel tetracyclic skeleton formed by a direct linkage between the quinone and sesquiterpene moieties. The configurations of these new compounds were assigned on the basis of combined NOESY and ECD analysis. These compounds exhibited cytotoxic and antimicrobial activities and weak inhibition against Na(+)/K(+)-ATPase.
Most of the previous studies reported that tacrolimus (TAC) with sirolimus (SRL) was associated with worse post-transplant outcomes in kidney transplantation, compared with TAC with mycophenolate ...mofetil (MMF). These might be attributable to high-dose SRL. However, outcomes using low-dose SRL with TAC for kidney transplantation are uncertain. The aim of this study was to assess the efficacy and safety of low-dose SRL with extended-release tacrolimus (ER-TAC) versus MMF with ER-TAC.
We randomly assigned 158 renal transplant patients to receive low-dose SRL or MMF in combination with ER-TAC and corticosteroid. The primary endpoint was the composite efficacy failure rate, including biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up, within 12 months post-transplantation. This trial is registered with ClinicalTrial.gov (number NCT01680952).
The efficacy failure rate was 6.6% in the low-dose SRL group and 13.3% in the MMF group in the intention-to-treat population (absolute difference, 6.8%; 95% confidence interval, -2.8% to 16.3%). The incidence of BPAR within 12 months post-transplantation was 5.3% in the low-dose SRL group and 13.3% in the MMF group (P = 0.09). The mean estimated glomerular filtration rate at 12 months post-transplantation was 53.2 mL/min/1.73 m2 in the low-dose SRL group and 52.4 mL/min/1.73 m2 in the MMF group (P = 0.76). The incidences of adverse events and serious adverse events were similar between groups.
Low-dose SRL with ER-TAC was not inferior to MMF with ER-TAC with respect to efficacy and safety. When used for immunosuppression in kidney transplantation, low-dose SRL with ER-TAC can effectively prevent acute rejection and preserve renal function.
To assess the feasibility and outcome of transjugular access for endovascular treatment of immature arteriovenous fistulae (AVFs).
Between August 2013 and January 2016, 90 patients (mean age, 64.5 y ...± 12.8) underwent endovascular treatment of immature AVFs via transjugular access. The mean age of fistulae was 3.3 months ± 1.8. Total procedure time and technical and clinical success rates of endovascular procedures were assessed. Primary and secondary patency rates were calculated according to the Kaplan-Meier method, and complications were assessed.
All patients had inflow lesions, among which 19 (21.1%) had occlusions. The juxtaanastomotic segment was the most common site (44.3%). Transjugular access was successful in 83 patients (92.2%), and 7 required additional standard or transarterial access. The mean procedure time was 36.5 minutes. Technical and clinical success rates were 98.9% and 90.5%, respectively. Mean primary and secondary patency durations were 14.3 months ± 1.7 and 31.0 months ± 0.7, respectively. Primary patency rates at 3, 6, and 12 months were 84.4%, 67.3%, and 48.8%, respectively. Secondary patency rates at 6 and 18 months were 98.6% and 95.5%, respectively. Venous rupture occurred as a result of balloon inflation in 9 patients (10%), and was managed by balloon tamponade. There were no complications related to transjugular access during a mean follow-up period of 12.6 months.
Transjugular access for angioplasty of immature AVFs is feasible and safe. Potential problems associated with access in the outflow vein could be avoided by transjugular access.
Gombaspiroketals A-C (1-3), tetracyclic sesterterpenes of a novel skeletal class, were isolated from the Korean marine sponge Clathria gombawuiensis. On the basis of the combined spectroscopic ...analyses, the structures of these compounds were determined to be highly rearranged sesterterpene spiroketal methoxyacetals (1 and 2) and a corresponding hemiacetal (3). The relative and absolute configurations were assigned by NOESY analysis and ECD calculations, respectively. These compounds exhibited moderate cytotoxicities and antibacterial activities.
The lowering of calcineurin inhibitor exposure is possibly considered as the proper strategy to prevent calcineurin inhibitor–induced nephrotoxicity in kidney transplant. This clinical study was ...designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) vs standard-dose tacrolimus with reduced-dose MMF.
A prospective, multicenter, open-label, randomized, and parallel-group clinical trial was conducted at 4 transplant centers in Korea. A total sample size was 108, and eligible patients were randomly assigned in a 1:1 ratio to either reduced-dose tacrolimus with standard-dose MMF (the study group) or standard-dose tacrolimus with reduced-dose MMF (the control group) for 6 months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure, and adverse events were compared.
The mean estimated glomerular filtration rate at 6 months post-transplantation was 69.83 ± 16.68 mL/min/1.73 m2 in the study group and 69.92 ± 17.55 mL/min/1.73 m2 in the control group (P > .05). The overall incidence of biopsy-proven acute rejection was 3.64% (n = 2) in the study group, compared to 3.77% (n = 2) in the control group (P > .05). There was no graft loss, death, or loss of follow-up in either group.
In conclusion, the results suggest that tacrolimus minimization with standard-dose MMF provides adequate immunosuppression with proper renal function and similar rate of incidence of acute rejection compared with the regimen including standard-dose tacrolimus with reduced-dose MMF.
Single-atom catalysts (SACs) featuring atomically dispersed metal cations covalently embedded in a carbon matrix show significant potential to achieve high catalytic performance in various ...electrocatalytic reactions. Although considerable advances have been achieved in their syntheses and electrochemical applications, further development and fundamental understanding are limited by a lack of strategies that can allow the quantitative analyses of their intrinsic catalytic characteristics, that is, active site density (SD) and turnover frequency (TOF). Here we show an
SD quantification method using a cyanide anion as a probe molecule. The decrease in cyanide concentration triggered by irreversible adsorption on metal-based active sites of a model Fe-N-C catalyst is precisely measured by spectrophotometry, and it is correlated to the relative decrease in electrocatalytic activity in the model reaction of oxygen reduction reaction. The linear correlation verifies the surface-sensitive and metal-specific adsorption of cyanide on Fe-N
sites, based on which the values of SD and TOF can be determined. Notably, this analytical strategy shows versatile applicability to a series of transition/noble metal SACs and Pt nanoparticles in a broad pH range (1-13). The SD and TOF quantification can afford an improved understanding of the structure-activity relationship for a broad range of electrocatalysts, in particular, the SACs, for which no general electrochemical method to determine the intrinsic catalytic characteristics is available.
Introduction
This prospective multicenter study aimed at investigating the safety and metabolic advantages of steroid withdrawal (SW) therapy in kidney transplant recipients with ...tacrolimus–mycophenolate mofetil‐based immunosuppression.
Methods
We analyzed 179 recipients who received kidney transplantation from March 2016 and September 2018. In 179 recipients, 114 patients maintained an immunosuppressive regimen including steroids (steroid continuation SC group). The remaining 65 patients were determined to withdraw steroid therapy after 6 months posttransplant (SW group). Metabolic parameters and graft functions of the two groups were evaluated.
Results
The estimated glomerular filtration rates at 12 months posttransplant were 67.29 ± 20.29 ml/min/1.73 m2 in SC group and 73.72 ± 17.57 ml/min/1.73 m2 in SW group (p < .001). The acute rejection occurred to four recipients in the SC group (3.5%) and no acute rejection occurred to SW group recipients during the 6–2 months posttransplant period. Oral glucose tolerance tests revealed that recipients in the SW group were more improved in glucose metabolism than the SC group during 6–12 months posttransplant. In addition, cholesterol levels and blood pressure decreased after the withdrawal of steroids in the SW group.
Conclusion
In conclusion, a 6‐month withdrawal of steroids in recipients with low immunological risk and stable graft function can be safely conducted and result in improvement of metabolic profiles. Stable recipients without biopsy‐proven acute rejection and proteinuria can safely withdraw from steroids out of a maintenance immunosuppressive regimen 6‐months posttransplant. A long‐term follow‐up study is needed to verify our results.
Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing ...strategy in de novo renal transplant recipients.
A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated.
One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1 ± 16.8 ml/min/1.73 m(2)) than that of the control group (60.6 ± 15.8 ml/min/1.73 m(2); P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups.
The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and additional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.
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