Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation

Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2^?/?, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation.

     

Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916)

BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II.     

Pesticide genotoxicity in cotton picking women in Pakistan evaluated using comet assay

To control agricultural pests and meet the increasing food demands, pesticides use has been increased substantially over time. Although pesticides are relatively specific to their targets, they can affect non-target organisms and are hazardous for the population around the application areas particularly to the individuals engaged in different types of agricultural activities. This situation is worse in developing and under-developed countries where personal protective equipment is merely used and regulatory guidelines are hardly practiced. In the present study, DNA damage in women exposed to pesticides while picking cotton with bare hands was assessed using single cell gel electrophoresis assay or comet assay. The presence of pesticides in blood serum of exposed individuals was also analyzed using high-performance liquid chromatography. Blood samples were collected from 138 (69 exposed and 69 control) randomly selected females from a major cotton growing area (Bahawalpur District) of the Punjab province of Pakistan. DNA damage, as determined by the mean comet tail length, was significantly higher (p?p?相似文献   

Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics

OBJECTIVES: Triclosan is in widespread use in domestic, commercial and healthcare settings and is used to reduce methicillin-resistant Staphylococcus aureus (MRSA) load in carriers. Triclosan resistance is uncommon, usually being due to mutation in fabI or overexpression of efflux pumps. This study investigated the ability of triclosan-containing silicone elastomer to kill MRSA adherent to its surface. METHODS: Silicone discs containing triclosan were prepared by a matrix-expansion method previously described. Discs were exposed to three strains of MRSA for 1 h for adhesion to take place. After incubation, discs were removed at intervals, sonicated and the sonicates analysed by chemiluminescence and viable counting. Survivors were found to consist of small colony variants (SCVs). These were then subjected to tests for known SCV characteristics and for susceptibility to triclosan. RESULTS: Viable counts fell until 51 h, when they began to increase, due to SCV. Of the three SCV strains, two showed impaired coagulase production and all showed reduced deoxyribonuclease production. None was auxotrophic. MICs of triclosan in the SCV rose by between 8- and 67-fold. CONCLUSIONS: Prolonged exposure of MRSA to triclosan-impregnated silicone, as in 'antimicrobial' plastics or catheters, resulted in the induction of SCV status and triclosan resistance. This has implications for industrial, medical and domestic use of polymers containing triclosan. SCVs are pathogenic and persistent. The widespread use of triclosan could lead to infection with MRSA SCVs, and new antimicrobials with physiological targets similar to that of triclosan might give rise to SCV resistance in clinical use.     

Antibiotics for the eradication of Propionibacterium acnes biofilms in surgical infection

OBJECTIVES: Propionibacterium acnes is increasingly recognized as a cause of delayed infection after spinal instrumentation or shunting for hydrocephalus. Biofilm development by this organism has recently been demonstrated. We therefore investigated the effect of two different courses of three antibiotics (penicillin, rifampicin and linezolid) on mature P. acnes biofilms in vitro. Outcomes were eradication or regrowth after withdrawal of antibiotics, simulating successful treatment and relapse. METHODS: P. acnes biofilms were grown on titanium discs for 6 days until mature, then exposed to the antibiotics for either 7 or 14 days before sonication and culture. Further, discs were similarly exposed, but after each course, they were reincubated for a further 9 days to check for regrowth. RESULTS: Penicillin, linezolid and linezolid plus rifampicin eradicated P. acnes biofilms after 14 days, but only penicillin had this effect after 7 days. 'Relapse' was prevented only by 14 day courses of penicillin or linezolid plus rifampicin, but not by linezolid alone. CONCLUSIONS: For P. acnes spinal instrumentation infections, either penicillin or linezolid plus rifampicin might be equally effective. For shunt infections, as penicillin does not give therapeutic cerebrospinal fluid concentrations, rifampicin plus linezolid might be the treatment of choice. Linezolid alone appears not to be as effective as penicillin against P. acnes biofilms.     

The association of alcohol use disorder with perioperative outcomes after primary total shoulder arthroplasty for glenohumeral osteoarthritis: a retrospective matched cohort study

BackgroundAccording to the World Health Organization, alcohol use disorder (AUD) is one of the leading mental health disorders in the United States. As the utilization of primary total shoulder arthroplasties (TSAs) continues to increase nationwide for the treatment of glenohumeral osteoarthritis (OA), studies evaluating the association of AUD with outcomes after primary TSA are warranted. Therefore, the aim of this study was to determine whether patients who undergo TSA and who have AUD have higher in-hospital lengths of stay (LOS), medical complications, and health care expenditures.MethodsThe Parts A and B 100% Medicare Claims Database were queried to identify patients who underwent primary TSA for glenohumeral OA and have AUD from January 1, 2005 to March 31, 2014. Patients were 1:5 ratio matched to a comparison cohort by age, sex, and various comorbid conditions. The query yielded 32,846 patients in the study (n = 5479) and comparison (n = 27,367) cohorts. The variables of interest include comparison of in-hospital LOS, 90-day medical complications, and day of surgery and 90-day health care costs. Welch’s t-tests were used to compare LOS, whereas multivariate logistic regression analyses were used to calculate the odds ratio (OR) of AUD on complications. A P value less than 0.001 was considered to be statistically significant.ResultsPatients with AUD had significantly longer in-hospital LOS (4 vs. 2 days, P < .0001), in addition to higher rates and odds of 90-day complications (30.44% vs. 7.94%; OR: 1.85, P < .0001) such as surgical site infections (1.15 vs. 0.24%; OR: 2.33, P < .0001), cerebrovascular accidents (5.06 vs. 1.23%; OR: 2.16, P < .0001), respiratory failures (5.79 vs. 1.52%; OR: 2.02, P < .0001), myocardial infarctions (1.53 vs. 0.43%; OR: 2.01, P < .0001), acute kidney injuries (6.55 vs. 1.34%; OR: 1.89, P < .0001), and other complications. In addition, patients in the study group incurred significantly higher day of surgery ($12,160.60 vs. $11,308.48, P < .0001) and 90-day episode of care costs ($14,493.13 vs. $13,087.55, P < .0001).ConclusionAs the prevalence of AUD continues to increase nationwide, understanding the association of AUD with outcomes after primary TSA for the treatment of glenohumeral OA is necessary. The current investigation is important as health care professionals and orthopedists can use this information to adequately educate patients on potential complications which may occur after their procedure.     

A Biomechanical Comparison of Fiberglass Casts and 3-Dimensional–Printed,Open-Latticed,Ventilated Casts

Background: The aim of this study was to quantify the stabilizing properties of a 3-dimensional (3D)-printed short-arm cast and compare those properties with traditional fiberglass casts in a cadaveric subacute distal radius fracture model. Methods: A cadaveric subacute fracture model was created in 8 pairs of forearms. The specimens were equally allocated to a fiberglass cast or 3D-printed cast group. All specimens were subjected to 3 biomechanical testing modalities simulating daily life use: flexion and extension of digits, pronation and supination of the hand, and 3-point bending. Between each loading modality, radiological evaluation of the specimens was performed to evaluate possible interval displacement. Interfragmentary motion was quantified using a 3D motion-tracking system. Results: Radiographic assessment did not reveal statistically significant differences in radiographic parameters between the 2 groups before and after biomechanical testing. A statistically significant difference in interfragmentary motion was calculated with the 3-point bending test, with a mean difference of 0.44 (±0.48) mm of motion. Conclusions: A statistically significant difference in interfragmentary motion between the 2 casting groups was only identified in 3-point bending. However, the clinical relevance of this motion remains unclear as the absolute motion is less than 1 mm. The results of this study show noninferiority of the 3D-printed casts compared with the traditional fiberglass casts in immobilizing a subacute distal radius fracture model. These results support the execution of a prospective randomized clinical trial comparing both casting techniques.