Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Bronchodilator responsiveness in children with primary ciliary dyskinesia

Background: Reversible airway obstruction is common in children with primary ciliary dyskinesia. However, the diagnostic value of adding bronchodilator (BD) response testing to routine spirometry is unclear. Methods: This is a retrospective analysis of pulmonary function test results obtained from children with primary ciliary dyskinesia seen as outpatients at the Hospital for Sick Children, Toronto. Spirometry results were collected for every appointment with BD response testing (“Visit”, with pre-BD and post-BD measurements) as well as for the previous (“Baseline”) and following (“Follow-up”) encounters. Results: A positive BD response was seen in 86 out of 474 (18.1%) of the pulmonary function tests from 82 children with primary ciliary dyskinesia. BD responsiveness was associated with a significant absolute change (±sd) in % predicted forced expiratory volume in 1 s (FEV$_{1}$) from Baseline to Visit pre-BD (−6.5±10.3%, p<0.001), but not from Baseline to Follow-up (0.4±10.8, p=0.757). Antimicrobial therapy was initiated more commonly following a Visit with a positive BD response (OR 3.8, 95% CI 2.2–6.6) compared to no BD response. Children with a positive BD response had a greater annual decline in FEV$_{1}$% predicted compared to those with no BD response (−0.9% per yearversus−0.5% per year, p<0.001). The annual decline in FEV$_{1}$% predicted was greater in children with multiple compared to one measured positive BD responses (−1.3% per yearversus−0.6% per year, p<0.001) and in those not treated with antibiotic therapy following a positive BD response compared to those treated with antibiotics (−1.1%versus−0.6%, p<0.001). Conclusion: A positive BD response in children with primary ciliary dyskinesia may help identify those at risk for accelerated lung disease progression

Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis

BACKGROUND: L-arginine is the common substrate for nitric oxide synthases and arginases. Increased arginase levels in the blood of patients with cystic fibrosis may result in L-arginine deficiency and thereby contribute to low airway nitric oxide formation and impaired pulmonary function. METHODS: Plasma amino acid and arginase levels were studied in ten patients with cystic fibrosis before and after 14 days of antibiotic treatment for pulmonary exacerbation. Patients were compared to ten healthy non-smoking controls. RESULTS: Systemic arginase levels measured by ELISA were significantly increased in cystic fibrosis with exacerbation compared to controls (17.3 ± 12.0 vs. 4.3 ± 3.4 ng/ml, p < 0.02). Arginase levels normalized with antibiotic treatment. Plasma L-arginine was significantly reduced before (p < 0.05) but not after treatment. In contrast, L-ornithine, proline, and glutamic acid, all downstream products of arginase activity, were normal before, but significantly increased after antibiotic therapy. Bioavailability of L-arginine was significantly reduced in cystic fibrosis before and after exacerbation (p < 0.05, respectively). CONCLUSION: These observations provide further evidence for a disturbed balance between the L-arginine metabolic pathways in cystic fibrosis

The dextral strike-slip Khlong Marui Fault, southern Thailand

The Khlong Marui Fault, lying to the NNE of Phuket, has a strong geomorphic signal, with marked fault-strike parallel topographic ridges. The fault is ca. 150 km long with a 210-030º trend. The lithologies within the strike-slip zone mainly consist of vertical layers of mylonitic metapelites, migmatitic gneiss, mylonitic granite, pegmatites and cataclasites. The foliation and stretching lineations in ductile rocks indicate a dextral strike-slip displacement at mid- to upper-crustal levels. Pegmatites cross-cut the mylonitic foliation but are in turn sheared at their margins, indicating synkinematic emplacement. Although clear age-constraints are still lacking, the dextral strike-slip kinematics of the Khlong Marui fault is likely to be related to the escape tectonics arising from the India-Asia collision

Quantitative kinematics of a frictional viscous lowangle normal fault on Kea (Western Cyclades, Greece)

Lithospheric extension during the Miocene is well documented in the Aegean. Within theCentral and Western Cyclades extension has been documented in detail by the formation ofMetamorphic Core Complexes and movement along low-angle normal faults (LANFs). Focusing on ahitherto unrecognised main low-angled fault geometry outcropping on northern Kea, this work presentspervasive evidence of top-to-south kinematics

Structural investigations along a low-angle normal fault zone (Kythnos, Greece)

Recent field investigations have revealed a high-strain zone in the south of Kythnos (Greece). Massive layers of ultrafine-grained Mn-rich calcitic mylonitic marbles and several generations of cataclasites hint at a high-strain event in the crust and are associated with a low-angle shear zone. We investigate fold-fault-relationships and deformation events preceding and post-dating normal faulting and compare the tectono-metamorphic history with adjacent islands in the Western Cyclades

Characteristics of low-angle normal faulting in Serifos (Western Cyclades, Greece)

On the island of Serifos SSW-directed low-angle faults accommodated crustal thinning during Miocene extension. Cross-cutting relationships suggest that the low-angle faults interacted with WNW-ESE striking conjugate high-angle normal faults in both the hanging and the footwall. Although high- and low-angle faults were likely synkinematic, the deformation mechanism differs significantly in both systems. The low-angle faults are characterized by several meters of low-grade, ultrafine grained marble mylonites below several decimetres of ultracataclasites. The high-angle faults represent mainly brittle deformation resulting in slickensides, cataclasites and pseudotachylites. The Ar/Ar mica geochronology yields uniform ages across the low-angle faults suggesting a nearly horizontal detachment at temperatures coincident with the brittle-ductile transition zone

Structural 3D modelling using GPR in unconsolidated sediments (Vienna basin, Austria)

In a gravel pit (SE Vienna basin), metre-thick bedded successions of conglomerate and sand layers ofMiocene age are exceptionally well exposed along a W-E-striking wall. The sediments are cut by numerous N-Sstriking,high-angle normal faults. The faults have a marked displacement gradient and offset marker layers of upto several metres. Using ground penetrating radar, we measured ten sections parallel to the W-E-striking wall inorder to construct a three-dimensional structural model. Exact positioning of the radargrams was achieved with thehelp of differential GPS and compilation of the data with a terrestrial laser scan of the outcrop

Miocene to Holocene exhumation of metamorphic crustal wedges in the NW Himalaya: evidence for tectonic extrusion coupled to fluvial erosion

[1] The Himalayan crystalline core zone exposed along the Sutlej Valley (India) is composed of two high‐grade metamorphic gneiss sheets that were successively underthrusted and tectonically extruded, as a consequence of the foreland‐directed propagation of crustal deformation in the Indian plate margin. The High Himalayan Crystalline Sequence (HHCS) is composed of amphibolite facies to migmatitic paragneisses, metamorphosed at temperatures up to 750°C at 30 km depth between Eocene and early Miocene. During early Miocene, combined thrusting along the Main Central Thrust (MCT) and extension along the Sangla Detachment induced the rapid exhumation and cooling of the HHCS, whereas exhumation was mainly controlled by erosion since middle Miocene. The Lesser Himalayan Crystalline Sequence (LHCS) is composed of amphibolite facies para‐ and orthogneisses, metamorphosed at temperatures up to 700°C during underthrusting down to 30 km depth beneath the MCT. The LHCS cooled very rapidly since late Miocene, as a consequence of exhumation controlled by thrusting along the Munsiari Thrust and extension in the MCT hanging wall. This renewed phase of tectonic extrusion at the Himalayan front is still active, as indicated by the present‐day regional seismicity, and by hydrothermal circulation linked to elevated near‐surface geothermal gradients in the LHCS. As recently evidenced in the Himalayan syntaxes, active exhumation of deep crustal rocks along the Sutlej Valley is spatially correlated with the high erosional potential of this major trans‐Himalayan river. This correlation supports the emerging view of a positive feedback during continental collision between crustal‐scale tectono‐thermal reworking and efficient erosion along major river systems

Reference values for exhaled nitric oxide (reveno) study

BACKGROUND: Despite the widespread use of fractional exhaled nitric oxide (FE(NO)) as a biomarker of airways inflammation, there are no published papers describing normal FE(NO )values in a large group of healthy adults. OBJECTIVE: The aim of this study was to establish adult FE(NO )reference values according to the international guidelines. METHODS: FE(NO )was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently. RESULTS: The main result of the study was the significant difference in FE(NO )values between men and women, thus indicating that gender-based reference FE(NO )values are necessary. The FE(NO )levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women. CONCLUSION: We propose reference FE(NO )values for healthy adult men and women that could be used for clinical and research purposes