Polysialylation and lipopolysaccharide‐induced shedding of E‐selectin ligand‐1 and neuropilin‐2 by microglia and THP‐1 macrophages

Microglia are tissue macrophages and mediators of innate immune responses in the brain. The protein‐modifying glycan polysialic acid (polySia) is implicated in modulating microglia activity. Cultured murine microglia maintain a pool of Golgi‐confined polySia, which is depleted in response to lipopolysaccharide (LPS)‐induced activation. Polysialylated neuropilin‐2 (polySia‐NRP2) contributes to this pool but further polySia protein carriers have remained elusive. Here, we use organotypic brain slice cultures to demonstrate that injury‐induced activation of microglia initiates Golgi‐confined polySia expression in situ. An unbiased glycoproteomic approach with stem cell‐derived microglia identifies E‐selectin ligand‐1 (ESL‐1) as a novel polySia acceptor. Together with polySia‐NRP2, polySia‐ESL‐1 is also detected in primary cultured microglia, in brain slice cultures and in phorbol ester‐induced THP‐1 macrophages. Induction of stem cell‐derived microglia, activated microglia in brain slice cultures and THP‐1 macrophages by LPS, but not interleukin‐4, causes polySia depletion and, as shown for stem cell‐derived microglia, a metalloproteinase‐dependent release of polySia‐ESL‐1 and polySia‐NRP2. Moreover, soluble polySia attenuates LPS‐induced production of nitric oxide and proinflammatory cytokines. Thus, shedding of polySia‐ESL‐1 and polySia‐NRP2 after LPS‐induced activation of microglia and THP‐1 macrophages may constitute a mechanism for negative feedback regulation. GLIA 2016 GLIA 2016;64:1314–1330     

One-screw fixation provides similar stability to that of two-screw fixation for type II dens fractures

Background

Anterior screw fixation has been widely adopted for the treatment of Type II dens fractures. However, there is still controversy regarding whether one- or two-screw fixation is more appropriate.

Questions/Purposes

We addressed three questions: (1) Do one- and two-screw fixation techniques differ regarding shear stiffness and rotational stiffness? (2) Can shear stiffness and rotational stiffness after screw fixation be restored to normal? (3) Does stiffness after screw fixation correlate with bone mineral density (BMD)?

Methods

We randomly assigned 14 fresh axes into two groups (seven axes each): one receiving one-screw fixation and another receiving two-screw fixation. Shear and torsional stiffness were measured using a nondestructive low-load test in six directions. A transverse osteotomy then was created at the base of the dens and fixed using one or two screws. Shear and torsional stiffness were tested again under the same testing conditions.

Results

Mean stiffness in all directions after screw fixation was similar in both groups. The stiffness after one- and two-screw fixation was not restored to normal: the mean shear stiffness restored ratio was less than 50% and the mean torsional stiffness restored ratio was less than 6% in both groups. BMD did not correlate with mean stiffness after screw fixation in both groups.

Conclusions

One- and two-screw fixation for Type II dens fractures provide similar stability but neither restores normal shear or torsional stiffness.

Clinical Relevance

One-screw fixation might be used as an alternative to two-screw fixation. Assumed BMD should not influence surgical decision making.     

Poor experience with a hinged endoprosthesis (WEKO) for the metacarpophalangeal joints: all 28 prostheses removed within 2 years in 8 patients having rheumatoid arthritis

We prospectively assessed the outcome of implanting a hinged prosthesis in destroyed metacarpophalangeal (MCP) joints (Larsen stage III-V). We implanted 28 cementless, axis-coupled total endoprostheses with hinging (WEKO prosthesis, Implant-Service GmbH, Hamburg, Germany) in 8 women (mean age 62 (47-80) years) suffering from rheumatoid arthritis. The mean follow-up period was 15 (12-18) months, and the evaluation was based on objective criteria, including joint motion, ulnar deviation of the long fingers, grip strength, radiographic migration and torsion of the prostheses, as well as the patients' subjective satisfaction. 12 months postoperatively, the mean arc of flexion was 30 (22-35) degrees, and the mean extension lag was 43 (40-48) degrees. Although no ulnar deviation was seen in 2 fingers, it was < 10 degrees in 3, between 10 degrees and 20 degrees in 7 of the fingers, and more than 20 degrees in 16. None of the patients could clench their fist firmly. We found prosthesis migration in 20 and torsion in 19 fingers. 2 years postoperatively, we had to remove all of the prostheses due to functional failure.     

Assessment of thoracic aortic dimensions in an experimental setting: comparison of different unenhanced magnetic resonance angiography techniques with electrocardiogram-gated computed tomography angiography for possible application in the pediatric population

PURPOSE: To compare different unenhanced magnetic resonance angiography (MRA) techniques for quantitative evaluation of vessel lumen in an experimental setting in young pigs whose dimensions allow for a comparison with a pediatric population. MATERIAL AND METHODS: Magnetic resonance imaging was performed in 5 healthy ventilated pigs at 1.5 T. Three different electrocardiogram (ECG)-triggered sequences were applied for MRA: [TSE-Db] T2-weighted dark-blood TurboSpinEcho (2.0 x 1.1 x 4 mm3); [trueFISP] 2D-steady-state-free-precession (2.2 x 1.8 x 2 mm3); [NAV] respiratory-gated, T2-prepared 3D-trueFISP (1.3 x 1.3 x 1.3 mm3). ECG-gated-CT angiography (CTA) (16-row CT, 1 mm collimation) served as the standard of reference. The vessel lumen was measured at 7 positions perpendicularly angulated to the vessel wall on multiplanar reformations: ascending aorta (P1), the aortic arch before (P2) and after (P3) the origin of the first supraaortic branch, the aortic arch after the origin of the second supraaortic branch (P4), the descending aorta at the level of the diaphragm (P5), and the first and second supraaortic branches (P6, P7). RESULTS: Percentage differences in the vessel area determined by MRA reformation compared with CTA-reformation were 10% +/- 20% and 35% +/- 27% (TSE-Db), -4% +/- 13% and 20% +/- 24% (trueFISP), and -3% +/- 13% and -10% +/- 19% (NAV), for positions P1 to P5 and P6 to P7, respectively. A significant difference from CTA was found for TSE-Db at all positions, and for trueFISP only at positions P6 and P7. CONCLUSIONS: Unenhanced MRA techniques allow for a reliable assessment of the dimensions of the thoracic aorta compared with CTA as the standard of reference. Using ECG-gating and navigator techniques, the free-breathing approach showed the best agreement with CTA. This technique may therefore be the most useful in the pediatric age group allowing for true 3D data acquisition with its inherent postprocessing possibilities.     

Four nonfatal and six fatal cases of opiate use: utility of morphine, its metabolites, and their ratios in blood specimens

Four nonfatal and six fatal cases of opiate use are presented with careful toxicological analysis. Levels of morphine (M), 6-monoacetylmorphine (6-MAM), morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) in blood specimens were measured by the sophisticated method of liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS). Fatal cases were characterized by much higher levels of free M than the nonfatal cases; this caused lower ratios of M6G/M and M3G/M in the fatal cases when compared with the nonfatal cases. Among the six fatal cases, the M6G/M ratios were especially low in four cases, in which rapid deaths were estimated. The present data are compared with data previously reported by other groups, and we discuss the utility of the levels of M, M6G, and M3G in blood and their ratios for estimating the antemortem status of each individual.     

Transpulmonary chemoembolization (TPCE) as a treatment for unresectable lung metastases

To evaluate tumor response after treating unresectable lung metastases with transpulmonary chemoembolization (TPCE) in palliative intention. From 2001 to 2005, 52 patients (mean: 59.8 years; 32 males/20 females) suffering from 106 unresectable lung metastases (mean:6 metastases/patient; range,1–21) were treated with 2–10 TPCE-sessions (mean: 3.3 sessions/patient). Metastases originated from primaries, including colorectal carcinoma (n = 20), breast cancer (n = 6), renal cellular carcinoma (n = 5), thyroid cancer (n = 4), cholangiocellular carcinoma (n = 2), leiomyosarcoma (n = 2), and others (n = 13). Tumor-feeding pulmonary arteries were selectively probed after puncturing the femoral vein, and administering 10 ml lipiodol, mitomycin C, and microspheres (Spherex) each via balloon catheter over pulmonary approach. During therapy, follow-up was accomplished at 4-week intervals using unenhanced and contrast-enhanced CT. After sequential therapy, follow-up was performed every 3 months for a period of 6 months up to 2.25 years. All patients tolerated the treatments well without major side effects or complications. In 24% (n = 13) moderate to high lipiodol uptake was found, while 75% (n = 39) of the tumors showed a low uptake. According to the RECIST criteria, “partial response” was achieved in 16 cases, “stable disease” in 11 cases, and “progressive disease” in 25 cases [mean survival: 17 months/median: 21.1 months (Kaplan-Meyer)]. According to these findings, TPCE is a well-tolerated procedure for palliative treatment of unresectable lung metastases.     

Transitional cell carcinoma of the renal pelvis presenting as a renal abscess

We report on a 76-year-old woman who was diagnosed with a primary renal abscess of the left kidney. After percutaneous drainage, no clinical improvement was observed. Surgical exploration and nephrectomy were performed. The histologic evaluation revealed an unsuspected transitional cell carcinoma of the renal pelvis, which had been misinterpreted as a primary renal abscess. Malignancy must be considered as an underlying cause for the formation of a renal abscess, especially if no other predisposing factors such as diabetes mellitus or urinary stones are present.     

Biomaterials as Scaffold for Bone Tissue Engineering

Abstract Almost 20 years after the invention of tissue engineering, autogenous bone grafting has remained the favored strategy for the treatment of bone defects. As an alternative, a vast variety of bone substitutes has been developed and is available for clinical use. The ongoing search for bone substitutes, however, reflects the limitations imposed to both autogenous and allogenous bone grafts as well as to bone substitute materials. The concept of tissue engineering holds great promise for the future treatment of osseous defects. Research in this interdisciplinary field is carried out to find a way of producing biologic substitutes as functional tissue replacement. For this, functionally active cells are applied on supporting scaffolds under controlled stimulation with growth factors. Scaffolds are temporary matrices for bone growth and provide a specific environment and architecture for tissue development. Ideally, scaffolds favor cellular attachment, growth and differentiation in vitro and in vivo. Especially ceramics and biodegradable polymers are widely used and have been tested in various animal studies. Yet, to allow for precise production of specific custom-made scaffolds, rapid prototyping (RP) techniques have recently drawn a lot of attention. Using these methods scaffolds with a predefined, well-controlled internal and external architecture mimicking the structure of natural bone can be generated. Although biocompatibility of the materials used in the process and the structural resolution that can be technically achieved so far limit the range of use, rapid manufacturing techniques do offer great opportunities to generate suitable scaffolds for bone tissue engineering in the near future.     

Bariatric surgery and work-up of the massive weight loss patient

Bariatric surgery remains the treatment of choice for the extremely obese patient, with an exponential growth in the number of procedures performed in response to the obesity epidemic. There are a variety of bariatric procedures available, which differ according to the method in which they achieve sustained weight loss. Plastic surgeons are beginning to see large numbers of patients who have undergone bariatric surgery and who have sustained massive weight loss (MWL) for evaluation of complex and lengthy-body contouring procedures. Proper evaluation of the patient who has sustained MWL requires an understanding of the physiologic impact of different bariatric procedures with particular knowledge of potential long-term nutritional complications.