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Cellular apoptosis, a common pathway towards tumor regression, is induced by many radiotherapy and chemotherapy regimens. Imaging methods that can detect apoptosis may be able to assess treatment response earlier than typical tumor volume measurements. In this paper, a wide range of diffusion experiments and a simple model of diffusion in tissues were used to probe the microstructural effects of apoptosis. Experiments were conducted on acute myeloid leukemia cell pellets, where apoptosis was induced by treatment with the chemotherapeutic agent cisplatin. Seventy-two hours following cisplatin treatment, pulsed and oscillating gradient diffusion measurements were utilized to assess effects across a broad range of structural scales. The presence of apoptosis, which was histologically confirmed by TUNEL (terminal deoxynucleotidyl transferase UTP nick end labelling) staining, significantly changed diffusion properties. To describe these changes, the data were fit to the parallel plane model, which characterizes the effects of restricted diffusion in terms of three parameters: d, the restricted size, Dfree, the intrinsic, free diffusion coefficient of the solvent, and Drest, the long time or 'restricted' diffusion coefficient. Apoptotic samples exhibited significant decreases in parameters d and Dfree and a significant increase in Drest. These changes appear consistent with the established morphological effects of apoptosis. In particular, the decrease in d may be a result of the combined effects of cell shrinkage, nuclear fragmentation and membrane blebbing, the decrease in Dfree may relate to cytosolic condensation, while the increase in Drest can be attributed to increased membrane permeability and extracellular volume fraction. By non-invasively detecting apoptosis, the methods reported in this study have the potential to improve upon current MRI methods for monitoring therapeutic response. Furthermore, these methods may offer sufficient specificity to differentiate between apoptosis and other modes of cell death, such as oncosis or necrosis. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multiecho T(2) relaxation measurements offer specific information about myelin content through the myelin water fraction (MWF), as well as about the water environments through the intra- and extra-cellular (IE), and global, geometric mean T(2) (GMT(2)) times. While these measurements have yielded new insights into brain development and pathologies, they have yet to be thoroughly investigated in the spinal cord. The goals of this study were: (1) to apply a new 3D multiecho T(2) relaxation measurement in the cervical spine with sufficient axial resolution to distinguish grey and white matter; (2) to perform a pilot reliability assessment of the resulting MWF and GMT(2) measures in a target population; and (3) to detect differences in these measures between a younger cohort (20-30 years of age) and an older cohort (50-75 years of age) of healthy adults. The results demonstrated that the MWF in younger healthy adults follows the known pattern of lower myelin content in grey matter (mean (95% confidence interval)) (0.049 (0.030-0.067)) as compared to white matter (0.296 (0.275-0.317), p<0.001). The reliability coefficients were 0.65 and 0.82 for the MWF in the dorsal (DC) and lateral column (LC) white matter, respectively; 0.79 and 0.52 for the IE GMT(2); and 0.74 and 0.73 for the global GMT(2). Significantly lower MWF were found in the older adults than in the younger adults (DC p=0.014; LC p=0.012), as well as lower IE GMT(2) times (DC p=0.008; LC p=0.042), however, the global GMT(2) times did not show any differences. These changes in MWF and IE GMT(2) times, but not in global GMT(2) times, indicate that multiecho T(2) relaxation measures are sensitive to changes in myelin integrity and cell morphology that may not be apparent on conventional T(2) weighted images., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In search of fluorinated functional groups which could undergo defluorination, and therefore be included in novel non-polluting fluorinated surfactants, omega-(bis(trifluoromethyl)amino)alkane-1-sulfonates (BTFMA-AS) with a homologue distribution from seven to thirteen methylene groups were synthesized and investigated for aerobic biodegradation applying both a standardized test and a fixed-bed bioreactor (FBBR). These compounds were prepared as part of a screening study for potentially mineralizable fluorinated endgroups.Application of hybrid triple quadrupole-linear ion trap mass spectrometry (QqQ(LIT)-MS) coupled to high-performance liquid chromatography (HPLC) allowed the tracking of primary degradation as well as the detection and structural elucidation of biotransformation intermediates. An understanding of the fragmentation pathway of the test compounds allowed selective precursor ion scans to reveal the presence of stable fluorinated metabolites. Structures were confirmed by enhanced product ion scans and MS(3) scans in the linear ion trap mode.The primary biodegradation rate and the extent of biodegradation were found to be chain-length dependent, with higher homologues being completely primarily degraded within 10 days. For the first time, two simultaneous metabolic pathways for substituted linear alkane-1-sulfonates were discovered: Desulfonation, oxidation to a carboxylic acid and subsequent chain-length shortening by beta-oxidation dominated the metabolism. This pathway resulted in the formation of 3-(bis(trifluoromethyl)amino)propionic acid and bis(trifluoromethyl)aminoacetic acid, which showed recalcitrance in this experiment. Oxidation of the alkyl chain to the respective carbonyl derivative represents the minor pathway. Only the long-chain homologues of these oxidized species were partially degraded; the short-chain homologues were not attacked.

As a new potentially mineralizable fluorinated surfactant, 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was synthesized and exposed to a standardized Zahn-Wellens test (OECD 302B). After the release of fluoride indicating the mineralization of the trifluoromethyl group, 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was subjected to a further biodegradation test carried out in a fixed bed bioreactor (FBBR). Evolution of biodegradation routes and pursuit was done by quadrupole linear ion trap mass spectrometer (QqLIT-MS) and quadrupole time-of-flight tandem mass spectrometer (QqTOF-MS). Biotransformation was initiated via hydroxylation in the alkyl chain at different positions. Hydroxy-9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was further oxidized with subsequent scission of the molecule forming mainly p-(trifluoromethyl)phenolate, which was mineralized releasing inorganic fluoride. These results demonstrate, that the new synthesized fluorosurfactant 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate is completely biotransformed. However, some intermediates, depending on the position of hydroxylation, impede further mineralization.

Proceeding from an estimation of the hitherto known models of the judgement of the coronary arteriosclerosis and the achieved degree of quantificability methodic principles are developed to quantify the influence of pathologo-anatomical parameters on the myocardial infarction with the help of mathematical methods using electronic data processing. With the help of the comparison of evaluation schemata according to Herzog/Schoenmackers and Romaniuk/Schroder on the basis of 174 hearts coronarographed post mortem a possibility is demostrated to estimate objectively the efficiency of evaluation schemata. The improvement of the evaluation after inclusion of the absolute mass of the heart is demonstrated. Herzog/Schoenmackers's valuation after the mathematical judgement of the probationers examined results in a wrong coordination of altogether 15 per cent, Romaniuk/Schroder's valuatiom results in 12.6 per cent. After the inclusion of the abolute mass of the heart into this valuation a decrease of the malcoordination to 10.3 per cent was achieved.

In order to objectify the judgement of the coronary arteriosclerosis the influence values position x obstruction on the left side and on the right side as well as the mass of the heart are mathematically valued with the aim to achieve a good separation between the infarction group and the control group and an insignificant false coordination of test persons. The optimation carried out for this purpose must be brought into accordance by means of technically ascertained recognitions and necessary practicability concerning valuations which are to be proposed. According to the results obtained on 174 test persons an obstruction on the right side below 50% has a higher importance than on the left side. In the positions of the obstruction the proximal as well as the medium third of the right coronary arteries a higher valuation must be ascribed. Compared with this the trunk of the left coronary artery has a significance corresponding possibly to the proximal third of this vessel. A more insignificant importance than hitherto taken into consideration belongs to the medium third of the left coronary artery. The valuations proposed lead to a highly significant improvement of the separation ability in contrast to the comparable valuations. The false coordination of the test persons at the same time decreases to 11 in the group with infarctions and to 2 in the control group. This equals 10.1 or 4.5%, respectively. In the present number of patients the barriers of the ostium and the type of supply have no statistically ascertained influence on the separation ability.

On the basis of the demonstrated mathematical valuations of pathologo-anatomical influence sizes on the defined myocardial infarction the model is extened by the calculation of total numbers for the purpose of simpler use in medical practice. The statistical influence of the characteristics on the formation of the arithmetical measure medium XI of the group with infarctions for the position of the stenosis times degree of stenosis is determined left-sided with 30.0% and right-sided with 42.3%, the heart mass is determined with 25.9% and the barriers of the ostium as well as the type of supply with 1.8%. For the judgment of the functional capacity of the developed model it is used in 126 intravitally coronarographed patients, in whom no myocardial infarction was to be proved. The false coordination is 4 cases (3.2%). Consequently, the developed model is evident not only for the initial material. It is usable post mortem and intravitally. Apart from the judgment of the severity of the stenosing coronary arteriosclerosis it serves intravitally for the estimation of the endangering by myocardial infarction. Criterion for the estimation of the degree of endangering is the distance from the point of separation TP = 558 (values of the arthmetical measure) and TP = 122 (total number).