Favorable outcome in a renal transplant recipient with donor-derived infection due to multidrug-resistant Pseudomonas aeruginosa

Most cases of donor-derived infection due to Pseudomonas aeruginosa reported in the literature are associated with vascular dehiscence, all of which resulted either in death or graft failure requiring graft removal. We report the successful treatment of donor-derived infection due to multidrug-resistant P. aeruginosa in a 64-year-old male who presented with bacteremia and peritransplant renal fluid collection after undergoing deceased-donor renal transplantation. As a result of the report of positive donor cultures by the host Organ Procurement Organization, the infection was promptly identified by blood cultures drawn before appearance of symptoms. Surveillance blood cultures in recipients are not usually recommended. However, they should be done if donor cultures turn positive. Therefore, it is crucial to perform cultures in donors and to closely follow them up for early identification and prompt treatment of donor-transmitted infections due to organisms like P. aeruginosa that can be graft and/or life threatening.     

齿科种植体钛的耐磨损性质探讨

目的：探讨齿科种植体材料钛的耐磨损性及其对种植体牙周维护的远期影响。方法：应用Martens划痕实验与超声洁牙机磨损实验对钛板进行耐磨损性检测。结果：Martens划痕实验与超声洁牙机磨损实验结果显示其在不同的荷重下均会对钛板造成不同程度的划痕及磨损。讨论：采用常规牙周维护方法可能会对钛种植体造成磨损,可能加重种植体表面上牙石及菌斑的沉积与结合,对钛种植体的远期预后产生不良影响。     

Breast cancer resistance protein (Bcrp) and the testis—an unexpected turn of events

Breast cancer resistance protein (Bcrp) is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens (e.g., genistein, daidzein, coumestrol), xenoestrogens and steroids (e.g., dehydroepiandrosterone sulfate). Bcrp is an integral membrane protein in cancer and normal cells within multiple organs (e.g., brain, placenta, intestine and testis) that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood–brain barrier located on endothelial cells near tight junctions (TJs). However, Bcrp is absent at the Sertoli cell blood–testis barrier (BTB); instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation (ES) in stage VI–early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F (filamentous)-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII–VIII tubules. These findings will be carefully evaluated in this brief review.     

Silver oxide‐containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia

Bacterial infection is a serious postoperative complication of joint replacement. To prevent infections related to implantation, we have developed a novel antibacterial coating with Ag‐containing hydroxyapatite (Ag‐HA). In the present study, we examined the antibacterial activity of Ag‐HA implant coatings in the medullary cavity of rat tibiae. Forty 10‐week‐old rats received implantation of Ag‐HA‐ or HA‐coated titanium rods, then were inoculated with ～1.0 × 10² colony‐forming units of methicillin‐resistant Staphylococcus aureus. Bacterial counts were calculated for rats euthanized at 24, 48, and 72 h postoperatively. Serum levels of Ag (in the Ag‐HA group only) were calculated for rats euthanized at 24, 48, 72 h and 4 weeks. Radiographic evaluations of bone infection were also performed at 4 weeks. Tibiae from both groups showing infection were evaluated histologically. Significant differences in bacterial counts were seen at 24, 48, and 72 h. Mean concentrations of Ag in serum peaked about 48 h after implantation, then gradually decreased. Mean radiographic scores for infection were significantly lower with Ag‐HA implants than with HA implants. Histological examination showed better results for abscesses, bone resorption, and destruction of cortical bone around Ag‐HA‐coated implants. These results indicate that Ag‐HA coatings may help prevent surgical‐site infections associated with joint replacement. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1195–1200, 2013     

Thalidomide for Treatment of Bleeding Angiodysplasias during Hemodialysis

Renal transplant patients are more prone to tuberculosis infection due to the underlying intense immunosuppression, with an incidence 20–74 times higher than that in the general population. It is associated with graft dysfunction and increased mortality rates. It can be frequently pulmonary but extra-pulmonary involvement is not rare, and in the latter case, it may be misinterpreted as genital malignancies. In this case report, we discuss a renal transplant patient with pelvic pain and fever, who was later diagnosed as having abdominopelvic tuberculosis.     

Treatment of Steroid‐Resistant Acute Renal Allograft Rejection With Alemtuzumab

Steroid‐resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid‐resistant renal allograft rejection treated with alemtuzumab (15–30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5‐4.0 mg/kg bodyweight i.v. for 10–14 days; n = 20). We assessed treatment‐failure (graft loss, lack of improvement of graft function or need for additional anti‐rejection treatment), infections during the first 3 months after treatment and infusion‐related side effects. In both groups, the median time‐interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff‐IIA or higher. Three alemtuzumab‐treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion‐related side‐effects in three alemtuzumab‐treated patients (27%), and more severe infusion‐related side effects in 17 RATG‐treated patients (85%, p = 0.013). Drug related costs of alemtuzumab‐treatment were lower than of RATG‐treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid‐resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion‐related side‐effects. These data warrant a prospective trial.     

Munc13 genotype regulates secretory amyloid precursor protein processing via postsynaptic glutamate receptors

The amyloid precursor protein (APP) can be proteolytically degraded via non-amyloidogenic α-secretase and amyloidogenic β-secretase pathways. Previously, we have identified the presynaptic protein Munc13-1 as a diacylglycerol/phorbolester (DAG/PE) receptor that contributes to secretory, non-amyloidogenic APP processing after PE stimulation. Here, we used organotypic brain slice cultures from wild-type mice and from Munc13-1 knock-out (KO), Munc13-2 KO and Munc13-1/2 double KO (DKO) mice for pharmacological stimulation experiments. First, we demonstrate that neuronal populations and synaptic components important for secretory APP processing develop normally in organotypic brain slice cultures of all genotypes analyzed. Blockade of voltage-gated Na⁺ channels by tetrodotoxin reduced the PE-stimulated secretory APP processing, whereas depolarization by high extracellular K⁺ concentration evoked APP secretion. Additionally, the PE-stimulated APP secretion from Munc13-1 KO brain slices was significantly lower than that from wild-type brain slices. This effect was not observed in brain slices from Munc13-2 KO mice, which is consistent with the lower abundance and subpopulation-specific distribution of Munc13-2 in presynaptic elements. In Munc13-1/2 DKO brain slices, the deficiency of Munc13-1 dominated the effect of APP processing. The Munc13-1 KO effect on APP processing could be rescued by the stimulation of postsynaptic glutamatergic receptors. This indicates that lack of postsynaptic glutamate receptor stimulation in Munc13-1 KO brain slice cultures but not presynaptic mechanisms account for compromised APP processing. We conclude that organotypic brain slices cultures are a valuable tool for studying APP processing pathways in intact neuronal circuits and that neuronal activity is important for maintenance of the non-amyloidogenic APP processing.     

Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem‐resistant Enterobacteriaceae

Vaborbactam (VAB; formerly RPX7009) is a novel beta‐lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta‐lactamases. It has been co‐formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug‐resistant nonfermenting gram‐negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa. The purpose of this article is to review existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro activity, and current progress in clinical trials of meropenem and VAB (MV). Phase 1 studies have demonstrated single and multiple doses of VAB up to 2000 mg, alone or in combination with meropenem 2000 mg administered as a prolonged infusion over 3 hours, are well tolerated with an adverse effect profile similar to that of meropenem monotherapy. The available data suggest preexisting resistance among KPC‐producing isolates is rare. Strains with elevated MICs have been characterized by multiple resistance determinants including porin defects, increased drug efflux, and increased blaKPC expression. It remains uncertain whether multifactorial resistance will emerge during MV treatment and with more widespread use. Early data are positive for complicated urinary tract infections and MV compared with best available therapy in patients with serious carbapenem‐resistant Enterobacteriaciae (CRE) infections. As clinicians contemplate how to incorporate MV into CRE treatment strategies, it will be important to track and understand resistance, discern the role, if any, of combination therapy in enhancing efficacy and/or preserving activity, and define the specific therapeutic niche of MV among the expanding anti‐CRE armamentarium.