Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He) measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with CT and lung function tests.

BACKGROUND: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV(1)) being the most accepted and used measurement. However, FEV(1) is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. PURPOSE: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. MATERIAL AND METHODS: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP (3)He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV(1) and carbon monoxide lung diffusion capacity [D(L,CO)]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). RESULTS: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP (3)He MR scanning was 3.8% (0.014 cm(2)/s [SD 0.024 cm(2)/s]; not significant). The time trends for FEV(1), D(L,CO), CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and D(L,CO) (P<0.001). CONCLUSION: This pilot study indicates the possible use of nonionizing HP (3)He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results.

(3) He Spin Filter for Neutrons.

The strongly spin-dependent absorption of neutrons in nuclear spin-polarized (3)He opens up the possibility of polarizing neutrons from reactors and spallation sources over the full kinematical range of cold, thermal and hot neutrons. This paper gives a report on the neutron spin filter (NSF) development program at Mainz. The polarization technique is based on direct optical pumping of metastable (3)He atoms combined with a polarization preserving mechanical compression of the gas up to a pressure of several bar, necessary to run a NSF. The concept of a remote type of operation using detachable NSF cells is presented which requires long nuclear spin relaxation times of order 100 hours. A short survey of their use under experimental conditions, e.g. large solid-angle polarization analysis, is given. In neutron particle physics NSFs are used in precision measurements to test fundamental symmetry concepts.

[Local oxygen supply to the cerebral cortex during thiopental and propofol anesthesia. First results]. / Lokale Sauerstoffversorgung des zerebralen Kortex während Thiopental-und Propofolanästhesie. Erste Ergebnisse.

Because the brain is highly vulnerable to damage from even a brief imbalance of oxygen delivery and demand, intraoperative disturbances of local oxygen supply must be avoided. Until now, there has been no method allowing fast and reliable intraoperative measurement of the local oxygen supply in the human brain. Intraoperative investigations were therefore performed using the Erlangen micro-lightguide spectrophotometer. METHODS. Intraoperative investigations of local intracapillary haemoglobin saturation (SO2) were performed during neurosurgical interventions using the Erlangen microlightguide spectrophotometer (EM-PHO). Measurements were performed in eight patients (age 31-67 years) during neurosurgical interventions. Three received thiopentone anaesthesia, and three received propofol. In two patients thiopentone anaesthesia was later changed to propofol. The EMPHO enables rapid, non-invasive measurement of local intracapillary SO2. White light from a Xenon-arc lamp is transmitted by a 250-microns micro-lightguide to the tissue. The remitted (reflected) light is led by 6 micro-lightguides surrounding the illuminating one to a rotating band-pass interference filter disk. Light in the range of 502 to 630 nm is detected with a photomultiplier. In this range haemoglobin shows an SO2-dependent spectrum, which is then analysed. Because the measurements are performed with micro-lightguides, high spatial resolution is attained. Representative measurements can be performed in a very short period of time (approx. 60 s); thus, the EM-PHO enables rapid monitoring of local SO2 in the brain. RESULTS. The effect of propofol and thiopentone anaesthesia on the distribution of local intracapillary haemoglobin saturation was investigated during neurosurgical interventions. The arterial PCO2 was similar in both groups (31 +/- 0.7 and 31 +/- 0.5 mmHg, respectively). There were also no differences in arterial blood pressure. The FiO2 was 0.28 +/- 0.04 in the thiopentone group and 0.30 +/- 0.1 in the propofol group. In all patients receiving propofol anaesthesia higher local SO2 values were found, even if the patients first received thiopentone (values in parenthesis). The mean local SO2 amounted to 65.4% (57.3%) in the propofol group and 38.8% (45.2%) in the thiopentone group. The number of values below 25% SO2 was 5.6% (5.8%) in the propofol group and 18.7% (19.1%) in the thiopentone group.

Enhanced release of nitric oxide causes increased cytotoxicity of S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside under hypoxic conditions.

S-Nitroso-N-acetyl-DL-penicillamine (SNAP) and sodium nitroprusside (SNP), both of which are known to release nitric oxide (.NO), exhibited cytotoxicity against cultivated endothelial cells. Under hypoxic conditions 5 mM SNAP and 20 mM SNP induced a loss in cell viability of about 90% and 80% respectively, after an 8 h incubation. Under normoxic conditions, cell death was only 45% and 42% respectively within the same time period. Concentrations of .NO liberated from SNAP and SNP were measured by the oxyhaemoglobin method and by two of the recently developed nitric oxide cheletropic traps (NOCTs). The .NO concentrations from SNAP and SNP increased from 74 microM and 28 microM to 136 microM and 66 microM respectively within 15 min of hypoxic incubation, and then decreased to 36 microM and 28 microM. In the respective normoxic incubations the .NO levels from SNAP and SNP remained in the region of about 30 microM and 20 microM respectively. In contrast, spermine/NO adduct (spermineNONOate) was shown to be more toxic under normoxic than under hypoxic conditions. Under either of these conditions, the concentration of .NO liberated from 2 mM spermineNONOate was about 20 microM. The results demonstrate that the cytotoxicity of SNAP and SNP, but not of spermineNONOate, is significantly enhanced under hypoxic compared with normoxic incubations. Studies on the .NO-releasing behaviour of these compounds indicate that the increased toxicity of SNAP and SNP under hypoxic conditions is related to the influence of O2 on the chemical processes by which .NO is produced from the precursors, rather than to an increased sensitivity of the hypoxic cells towards .NO.

Nuclear magnetic resonance spectra and molecular structure of mesna.

Mesna (2-mercapto-ethane sulfonic acid sodium salt) is used as a reliably acting uroprotector in cancer chemotherapy with oxazaphosphorine cytostatics. 1H-, 13C[1H]- and C,H-COSY-NMR-spectra are analyzed. In solution state mesna exists predominantly in a trans-rotameric form. These findings are supported by hypothetical gas-phase-structures of mesna, simulated via the program system MOPAC.

Low toxicity of nitric oxide against endothelial cells under physiological oxygen partial pressures.

Cultured rat liver endothelial cells were incubated with 1 and 2 mM spermineNONOate at different O2 concentrations in the incubation atmosphere. (Z)-1-{N-[3-Aminopropyl]-N-[4-(3-aminopropylammonio) butyl]-amino}diazen-1-ium-1,2- diolate (spermineNONOate), at 2 mM, was highly cytotoxic at 21% and 95% O2 (as measured by lactate dehydrogenase release); more than 80% of the cells were damaged after 6 h of incubation. Cytotoxicity induced by 2 mM spermineNONOate was significantly decreased at 10%, 5% and 0% O2; cell death was 54%, 36% and 25% respectively after 6 h of incubation. In contrast, 1 mM spermineNONOate was almost non-toxic towards the cells. Only at 95% O2 was a slight damaging effect, of 25%, observed. The nitric oxide (.NO) concentrations released from 1 and 2 mM spermineNONOate were determined as varying between 5 and 12 microM and between 12 and 22 microM respectively as measured by the oxyhaemoglobin and the NO cheletropic spin-trapping methods. The decomposition rate of spermineNONOate and the resulting .NO concentrations were independent of O2 at all applied concentrations. Likewise, the steady-state concentrations of H2O2 remained at approx. 1 nM at all O2 concentrations, as measured with the fluorescent dye scopoletin. L-Tyrosine and L-ascorbate, both of which are known to scavenge reactive nitrogen species, markedly diminished spermineNONOate-induced cytotoxicity at 95% O2. The formation of 3-nitrotyrosine, indicating the reaction of L-tyrosine with nitrogen dioxide (.NO2) and/or peroxynitrite anions, was enhanced in incubations with spermineNONOate at 21% and 95% O2. The results demonstrate that at O2 partial pressures typically found under physiological conditions and at .NO concentrations that can occur in vivo, .NO alone is almost non-toxic towards cultured rat liver endothelial cells. .NO at these concentrations in vivo, however, exerts toxic effects at supraphysiological O2 partial pressures, owing to its oxidation to reactive nitrogen species such as .NO2.