Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Meeting report: International workshop on endocrine disruptors: Exposure and potential impact on consumers health

The French Agency for Food, Environmental and Occupational Health and Safety (Anses) hosted a two-day workshop on Endocrine Disruptors: Exposure and Potential Impact on Consumers Health, bringing together participants from international organizations, academia, research institutes and from German, Swedish, Danish and French governmental agencies. The main objective of the workshop was to share knowledge and experiences on endocrine disruptors (ED) exposure and potential impact on consumers’ health, to identify current risk assessment practices and knowledge gaps and issue recommendations on research needs and future collaboration. The following topics were reviewed: (1) Definition of ED, (2) endpoints to be considered for Risk assessment (RA) of ED, (3) non-monotonic dose response curves, (4) studies to be considered for RA (regulatory versus academic studies), (5) point of departure and uncertainty factors, (6) exposure assessment, (7) regulatory issues related to ED. The opinions expressed during this workshop reflect day-to-day experiences from scientists, regulators, researchers, and others from many different countries in the fields of risk assessment, and were regarded by the attendees as an important basis for further discussions. Accordingly, the participants underlined the need for more exchange in the future to share experiences and improve the methodology related to risk assessment for endocrine disrupters.     

Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess

Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive‐aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels.     

Relationship between glucose oxidation and glucose tolerance in man

The study was performed to determine the influence of peripheral glucose utilization on glucose tolerance. Glucose oxidation was measured in a group of 6 normal subjects by means of continuous indirect calorimetry during a 100 g oral glucose tolerance test for 3 hr, comparing the control state with experimental inhibition or stimulation of glucose oxidation. Suprabasal oxidation, corresponding to oxidation in response to the load, mainly by insulin-dependent tissue, was obtained by subtracting basal oxidation (essentially by non-insulin dependent tissues) from total oxidation. Suprabasal oxidation of glucose was inhibited by a neutral fat infusion, and stimulated by means of dichloracetate. In the control test, from the 100 g glucose administered, 18 g participated to suprabasal oxidation during the 3 hr of the test. A neutral fat infusion, started 2 hr before the glucose load and lasting throughout the test, decreased suprabasal oxidation to 7.5 g, i.e. to 42% of the control value. With the fat infusion, a larger fraction of the energy consumption was shown to originate from lipid oxidation (37% versus 25% in controls, p < 0.05) at the expense of carbohydrate (CHO) oxidation (44% versus 60% in controls, p < 0.05). However, these major changes in peripheral glucose oxidation were accompanied by only a moderate decrease in glucose tolerance. Dichloracetate administered prior to the test increased suprabasal oxidation to 25 g glucose oxidized in the 3 hours following the glucose load, i.e. an increment of 39% above the control value. A larger fraction of energy consumption was derived from carbohydrates (77% versus 60% in controls, p < 0.05). However, no significant change was observed in glucose tolerance. These results indicate that marked changes of peripheral glucose oxidation have little influence on glucose tolerance and suggest that another mechanism, i.e. glucose storage, plays a larger role in regulating plasma glucose levels during oral glucose tolerance tests.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

The Pseudomonas aeruginosa LasB metalloproteinase regulates the human urokinase-type plasminogen activator receptor through domain-specific endoproteolysis

Pseudomonas aeruginosa is an opportunistic pathogen in human lungs, where its secretable LasB metalloproteinase can be a virulence factor. The urokinase-type plasminogen activator receptor (uPAR) participates in pericellular proteolysis and the adherence/migration of epithelial cells and leukocytes recruited during infection and shows functional regulation by various proteinases via limited endoproteolysis occurring within its three domains (D1 to D3). We thus examined the proteolytic activity of LasB on uPAR by using recombinant uPAR as well as uPAR-expressing, human monocytic, and bronchial epithelial cell lines. Protein immunoblotting and flow immunocytometry using a panel of domain-specific anti-uPAR antibodies showed that LasB is able to cleave uPAR both within the sequence linking D1 to D2 and at the carboxy terminus of D3. Comparison of LasB-producing and LasB-deficient bacterial strains indicated that LasB is entirely responsible for the uPAR cleavage ability of P. aeruginosa. Based on amino-terminal protein microsequencing and mass spectrometry analysis of the cleavage of peptides mimicking the uPAR sequences targeted by LasB, cleavage sites were determined to be Ala(84)-Val(85) and Thr(86)-Tyr(87) (D1-D2) and Gln(279)-Tyr(280) (D3). Such a dual cleavage of uPAR led to the removal of amino-terminal D1, the generation of a truncated D2D3 species, and the shedding of D2D3 from cells. This proteolytic processing of uPAR was found to (i) drastically reduce the capacity of cells to bind urokinase and (ii) abrogate the interaction between uPAR and the matrix adhesive protein vitronectin. The LasB proteinase is thus endowed with a high potential for the alteration of uPAR expression and functioning on inflammatory cells during infections by P. aeruginosa.