Metalloproteinase levels are decreased in symptomatic carotid plaques

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.     

First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis.

The first identification of anatoxin-a in a French lotic system is reported. Rapid deaths of dogs occurred in 2003 after the animals drank water from the shoreline of the La Loue River in eastern France. Sediments, stones and macrophytes surfaces at the margin of the river were covered by a thick biofilm containing large quantities of several benthic species of filamentous, non-heterocystous cyanobacteria. Known cyanotoxins, such as microcystins, saxitoxins and anatoxins were screened from biofilm samples by biochemical and analytical assays. A compound with similar UV spectra to the anatoxin-a standard was detected by high-performance liquid chromatography (HPLC) coupled with photo-diode array detector. This toxin was further identified by HPLC coupled with a UV detector and by electrospray ionisation-Quadrupole-Time-Of-Flight mass spectrometer, and confirmed by tandem mass spectrometry. These two techniques were necessary to discriminate anatoxin-a in phenylalanine-containing matrices such as liver samples of poisoned dogs. The toxin and the aromatic amino acid, phenylalanine, present the same pseudomolecular ion at m/z 166, but have differing fragmentation patterns, retention times and UV spectra. Finally, several cyanobacterial strains were isolated from the green biofilm and tested for anatoxin-a production. Phormidium favosum was identified as a new anatoxin-a producing species.     

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis.

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.     

Do seasonal changes affect metallothionein induction by metals in mussels, Mytilus edulis?

Mussels have been proposed as biomonitors of metal pollution based on the determination of metallothionein (MT) concentrations as a biomarker, but a comprehensive study taking into account both intersite and long-term temporal variations in MT and metal concentrations in different organs is lacking. Thus, the present study was designed to examine the concentrations of cytosolic and insoluble Cd, Cu, Zn, and MT in gills and digestive gland of mussels (Mytilus edulis) of homogeneous size and age obtained from aquaculture and kept on a reference site or translocated to a metal-rich site throughout their reproductive season (March-October 1997). Relatively significant binding of metals to the insoluble fraction was observed in both tissues. In the digestive gland, monthly MT concentrations were strongly correlated to cytosolic metal levels. Moreover, despite significant temporal variations, the grand mean MT concentration based on all individual determinations in the digestive gland (reference, n=54; transplants, n=50) was significantly higher in mussels from the metal-rich site. On the other hand, gill MT concentrations did not reflect metal contamination as reliably.     

Inhibition of bone turnover by milk intake in postmenopausal women

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.     

Effects of Air Pollution on Adults with Chronic Obstructive Pulmonary Disease

Few studies have been conducted on the effects of air pollution on patients with chronic obstructive pulmonary disease (COPD). During a 14-mo period, 39 Parisian adults with severe COPD were monitored by their physicians. Daily levels of 4 air pollutants were provided by an urban air-quality network. Exacerbation of COPD was associated only with ozone (O₃) (odds ratio [OR] = 1.44 for a 10-μg/m³ increase in O₃; 95% confidence interval [Cl] = 1.14, 1.82), with a lag of 2-3 days. The effect of O₃ was greater in patients whose carbon dioxide pressure (PaCO₂) was higher than 43 mm Hg (OR = 1.83; 95% Cl = 1.36, 2.47) vs. those with a lower PaCO₂ (OR = 1.26; 95% Cl = 0.90, 1.77). The effect of O₃ was unchanged, regardless of the maintenance medications used. The only air pollutant to which patients with severe COPD were particularly sensitive was O₃.     

Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain

Background

Evaluation of stable symptomatic outpatients with suspected coronary artery disease (CAD) may be challenging because they have a wide range of cardiovascular risk. The role of troponin testing to assist clinical decision making in this setting is unexplored.

Variations in Digestive Physiology of Rats After Short Duration Flights Aboard the US Space Shuttle

The purpose of this work was to assess the influence of microgravity on several endogenous and microbial parameters of digestive physiology. On the occasion of two Spacelab Life Sciences missions, SLS-1 (a 9-day space flight) and SLS-2 (a 14-day space flight), Sprague-Dawley rats flown aboard the US space shuttle were compared to age-matched ground-based controls. In both flights, exposure to microgravity modified cecal fermentation: concentration and profile of short-chain fatty acids were altered, whereas urea and ammonia remained unchanged. Only in SLS-1 was there an induction of intestinal glutathione-S-transferase. Additional analyses in SLS-2 showed a decrease of hepatic CYP450 and of colonic goblet cells containing neutral mucin. After a postflight recovery period equal to the mission length, only modifications of the hepatic and intestinal xenobiotic metabolizing enzymes still persisted. These findings should help to predict the alterations of digestive physiology and detoxification potential likely to occur in astronauts. Their possible influence on health is discussed.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.