Ellipsoidal coil for magnetic resonance spectroscopy

We developed an ellipse-shaped surface coil for magnetic resonance spectroscopy for a 1.5 T clinical MR Imager. This coil is to be used to obtain spectra from arms and legs. Standard volume and single-loop coils provide a poor signal because they can not be placed close to the region of interest and their shapes do not fit the anatomy of human extremities. The coil design proposed has more anatomical shape which allows to be placed closer to the region of interest. A higher signal-to-noise ratio can then be achieved resulting in better-quality spectra. Spectra from a phantom and from the arm of a healthy volunteer were acquired to show viability, A 1.5 T clinical scanner (Signa LX equipped with V. 5.8, General Electric Medical System) together with standard spin-echo sequences were used to perform all the spectroscopy experiments. This receiver coil can generate high resolution MR spectra of a spectroscopy phantom and is fully compatible with clinical magnetic resonance systems and standard pulse sequences

Increased expression of gelatinases and collagenase in rat lungs exposed to 100% oxygen

Exposure of adult rats to 100% O-2 produces a lethal injury by 72 h. We reasoned that matrix metalloproteinases participate in the pathogenesis of hyperoxic lung injury. To that end we studied the expression and activity of gelatinases A and B and interstitial collagenase in lung tissues and bronchoalveolar ravage fluids (BALF) of rats exposed to 100% oxygen for 60 h. Gelatin zymography of BALF samples revealed a similar to 72 kDa molecular species both in controls and oxygen-exposed animals. In addition, BALF from hyperoxic rats exhibited a 95-kDa gelatinase. Likewise, BALF total gelatinolytic and collagenolytic activities were significantly increased in oxygen-exposed rats. In situ hybridization revealed an increase in type IV collagenases as well as interstitial collagenase mRNAs in the oxygen-exposed lungs. The three enzymes were expressed by alveolar macrophages, and in variable degrees by interstitial and alveolar epithelial cells. Immunoreactive gelatinase B and collagenase paralleled the cell localization of the mRNAs but were also detected in the alveolar walls and interstitium. In situ zymography showed gelatinolytic activity in frozen sections of oxygen-exposed lungs but not in normal lungs. The upregulation of these metalloproteinases during acute exposure to 100% O-2 suggests that they might contribute to hyperoxic lung damage through the degradation of extracellular matrix components

TIMP-1,-2,-3, and-4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment?

Fibroblast proliferation and extracellular matrix accumulation characterize idiopathic pulmonary fibrosis (IPF). We evaluated the presence of tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, and -

Increase of lung neutrophils in hypersensitivity pneumonitis is associated with lung fibrosis

Hypersensitivity pneumonitis (HP) is characterized by a T-cell-mediated alveolitis, and the putative role of other inflammatory cells in its pathogenesis remains unclear. In this study we determined whether increased quantities of neutrophils were present in HP lungs, and if they were positive for gelatinase B and collagenase-2. Fifteen nonsmoking patients with subacute/chronic active HP were included. Lung samples were analyzed using myeloperoxidase antibody, and neutrophil/total cell ratio was evaluated by digital processing. All HP tissue samples exhibited variable quantities of neutrophils located inside vessels, and in the interstitial and alveolar spaces. Lung neutrophil percentage ranged from 0.7% to 4.8% (2.1 +/- 1.4%). There was a positive correlation between the percentage of lung neutrophils and the percentage of lung fibrosis (r = 0.6, p < 0.02). Tissue neutrophils showed intense immunoreactive collagenase-2 and gelatinase B staining. Additionally, gelatinolytic activities corresponding to progelatinases A and B and their activated forms, were several-fold increased in the bronchoalveolar lavage fluid (BALF) from patients with HP as compared with control subjects. These findings suggest that in HP lungs there is a persistent traffic of neutrophils loaded with gelatinase B and collagenase-2 that may play a role in the lung damage and in the fibrotic response

Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase

We examined the expression of interstitial collagenase and its enzymatic activity in lung damage induced by tobacco smoke. Guinea pigs were exposed to the smoke of 20 cigarettes per day from 1-8 wk. Age-matched guinea pigs were used as controls. At 6 and 8 wk of smoke exposure, lungs exhibited interstitial and peribronchiolar inflammation and moderate emphysematous changes. In situ hybridization of injured lungs revealed patchy expression of collagenase mRNA mainly in macrophages but also in alveolar epithelial and interstitial cells. Immunoreactive protein was detected in alveolar macrophages and in the alveolar walls and interstitium. Collagenolytic activity increased beginning in the 4th wk of exposure (0.7 +/- 0.43 mu g collagen degraded/mg collagen incubated relative to 0.23 +/- 0.14 in control

Bleomycin-induced pulmonary fibrosis is attenuated in gamma-glutamyl transpeptidase-deficient mice

To investigate repair mechanisms in bleomycin-induced pulmonary fibrosis, we used mice deficient in gamma-glutamyl transpeptidase (GGT(-/-)), a key enzyme in glutathione (GSH) and cysteine metabolism. Seventy-two hours after bleomycin (0.03 U/g), GGT-/- mice displayed a different inflammatory response to wild-type mice as judged by a near absence of neutrophils in lung tissue and bronchoalveolar lavage and a less pronounced rise in matrix metalloproteinase-9. Inflammation in GGT(-/-) mice consisted mainly of lymphocytes and macrophages. At 1 month, lungs from bleomycin-treated GGT(-/-) mice exhibited minimal areas of fibrosis compared with wild-type mice(light microscopy fibrosis index: 510 +/- 756 versus 1975 +/- 817, p < 0.01). Lung Collagen content revealed a significant increase in bleomycin-treated wild-type (15.1 +/- 3.8 versus 8.5 +/- 0.7 mug hydroxy(OH)-proline/mg dry weight, p < 0.01) but not in GGT(-/-)(10.4 +/- 1.7 versus 8.8 +/- 0.8). Control lungs from GGT(-/-) showed a significant reduction of cysteine (0.03 +/- 0.005 versus 0.055 +/- 0.001, p < 0.02) and GSH levels (1.24 +/- 0.055 versus 1.79 +/- 0.065, p < 0.002). These values decreased after 72 hours of bleomycin in both GGT-/- and wild-type but reached their respective control values after I month. Supplementation with N-acetyl cysteine partially ameliorated the effects of GGT deficiency. These findings suggest that increased neutrophils and matrix metalloproteinase-9 during the early inflammatory response and adequate thiol reserves are key elements in the fibrotic response after bleomycin-induced pulmonary injury

The mental health care gap in Intellectual Disabilities in Spain: Impact analysis and knowledge to action plan

BACKGROUND: Intellectual developmental disorder or Intellectual disability (ID) is a prevalent condition with a high impact along the life-span particularly when associated to other mental disorders (MD). SPECIFIC AIM: To estimate the unmet needs and to design a knowledge to action plan to reduce the care gap in ID-MD in Spain. METHOD: We followed a 5-step `maxi' impact assessment and a mixed qualitative/quantitative design including expert panels, secondary analysis of databases and a prospective survey in the 17 regions in Spain. Schizophrenia was used as comparator due to similar prevalence rates and burden. RESULTS: Persons with ID-MD had ten times less outpatient contacts and hospital admissions than patients with schizophrenia. The outpatient case load was 2.31% in ID and 14.6% in schizophrenia. ID had the lowest hospitalization rate amongst all mental disorders but the highest length of stay. The expert panel estimated that half of persons with ID-MD are not adequately assessed and 95% do not receive the required care in Spain. Basic care needs include 6.5 beds and an ID-MD outpatient service per 1 million population. At least 134 specialized psychiatrists and psychologists and 277 beds are needed to reach the minimum standards in Spain. CONCLUSION: This study quantifies the ID-MD care gap in Spain and the basic specialized services needed. In spite of the societal and health implications of ID-MD the knowledge-to-action plan had a modest impact limited at the regions where ID-MD programmes were already implemented. IMPLICATIONS FOR HEALTH POLICY: Specific priority setting on ID-MH should be incorporated to mental health strategy at the Ministry of Health within a broader health and ID plan. National and regional policies should incorporate an integrative care approach through the life cycle. The development of excellence centers on ID-MD and a national observatory on this topic should be encouraged