PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL- 8 production by alveolar epithelial cells in culture

OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.     

An intra-articular vascular malformation with a ganglion in a knee

We report a case of an intra-articular vascular malformation occurring simultaneously with a ganglion in a knee joint. We believe this to be the first reported case of an intra-articular vascular malformation occurring simultaneously with a ganglion. The malformation was cauterized resulting in resolution of knee pain. We suggest that vascular malformations be considered in the differential diagnosis of knee pain.     

Aortopulmonary window with patent ductus arteriosus and interrupted aortic arch: A case report

Indian Journal of Thoracic and Cardiovascular Surgery -     

Cardiovascular beta-adrenoceptor sensitivity of undernourished subjects

1. Eleven normal-weight male subjects (weight/height2 (W/H2) 19.0-22.5) from a good socio-economic background and on ad lib. food intake, and eight undernourished male labourers (W/H2 16.4-18.6) on low energy intakes, were studied. 2. Comparison of cardiovascular responses to increasing single doses of the beta-agonist, isoproterenol, showed a significantly greater positive chronotropic dose response in the undernourished subjects. 3. Cardiovascular responses to head-up tilt were similar in both the normal-weight and undernourished subjects. 4. Undernourished individuals may show an increase in beta-adrenoceptor sensitivity which may be akin to a denervation type of supersensitivity as a result of a nutrition-related reduction in sympathetic activity.     

Neurilemmoma of tongue

Neurilemmoma is usually soimry, benign tumour derived from schwan cells of the Sheaths of peripheral cranial or autonomie nerves. In thehead and neck region it occurs most commonly in association with acoustic nerve within the skuil and is rely fottnd in the oral cavity (1,2). We report here two cases of the iongue diagnosed on histopathohgy.     

Variability in cardiovascular and plasma norepinephrine responses to head-up tilt in healthy human subjects.

Eight healthy, young adult males underwent three separate, 10-min 70 degrees head-up tilts (HUT) over a period of nine days, in order to assess the intra- and inter-individual variability of cardiovascular and plasma norepinephrine (NE) responses to the manoeuvre. Cardiovascular parameters and plasma NE were measured in the basal state and at 2-min intervals during the HUT. The results indicate that: (1) the intra-individual variability is a smaller component of the total variability of both cardiovascular and plasma NE responses to HUT; (2) the variability in cardiovascular parameters is smaller than that in plasma NE levels, both basal and in response to postural stress; (3) there does not appear to be any difference in variability when expressed either as the maximal or the mean response to HUT; and (4) there does not appear to be an increase in the variability of the measured parameters over the duration of the HUT.