Diffusion tensor imaging findings in the multiple sclerosis patients and their relationships to various aspects of disability.

BACKGROUND: The aim of the study was to assess microstructural changes within strategic brain regions in multiple sclerosis (MS) patients, using diffusion tensor imaging (DTI), with regard to various aspects of disability. MATERIAL AND METHODS: The study comprised 50 patients with relapsing-remitting MS (37 women, 13 men, mean age 36.4 yrs) and 27 age- and sex-matched controls. Using DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained within corpus callosum (CC), both thalami (TH) and middle cerebellar peduncles (MCP). Disability was assessed using Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), Symbol Digit Modalities Test (SDMT) and Fatigue Severity Scale (FSS). DTI indices were compared between the patients and controls and in the MS group - referred to disability measures. RESULTS: Significant decrease in FA and increase in ADC within CC and both TH were found in MS patients compared to the controls. DTI indices within CC and TH correlated significantly with SDMT score, and within TH and MCP - with MSFC manual dexterity measure. CONCLUSIONS: Changes in DTI measures in normal appearing white and grey matter in the MS patients indicate subtle alterations of the tissue integrity. An occult damage to the strategic brain regions may contribute to various aspects of disability due to MS.

Role of Diffusion Tensor MR Imaging in Degenerative Cervical Spine Disease: a Review of the Literature.

In the article we review the current role of diffusion tensor imaging (DTI), a modern magnetic resonance (MR) technique, in the diagnosis and the management of cervical spondylotic myelopathy (CSM), the most serious complication of degenerative cervical spine disease (DCSD). The pathogenesis of DCSD is presented first with an emphasis placed on the pathological processes leading to myelopathy development. An understanding of the pathophysiological background of DCSD is necessary for appropriate interpretation of MR images, both plain and DTI. Conventional MRI is currently the imaging modality of choice in DCSD and provides useful information concerning the extent of spondylotic changes and degree of central spinal canal stenosis; however its capability in myelopathy detection is limited. DTI is a state of the art imaging method which recently has emerged in spinal cord investigations and has the potential to detect microscopic alterations which are beyond the capability of plain MRI. In the article we present the physical principles underlying DTI which determine its sensitivity, followed by an overview of technical aspects of DTI acquisition with a special consideration of spinal cord imaging. Finally, the scientific reports concerning DTI utility in DSCD are also reviewed. DTI detects spinal cord injury in the course of DCSD earlier than any other method and could be useful in predicting surgical outcomes in CMS patients, however technical and methodology improvement as well as standardization of acquisition protocols and postprocessing methods among the imaging centers are needed before its implementation in clinical practice.

Robertsonian polymorphism in the common shrew (Sorex araneus L.) and selective advantage of heterozygotes indicated by their higher maximum metabolic rates.

Some cases of Robertsonian (Rb) polymorphism in the common shrew (Sorex araneus L.) are believed not to be associated with hybrid zones. One of the hypotheses explaining the persistence of such Rb polymorphism is that they are maintained by some form of selection for Rb heterozygotes. To test this hypothesis, we compared several parameters between homozygotes and Rb heterozygotes for the mp chromosome pair. We used shrews from Jurowce population in Poland, situated within the range of the Bialowieza race, where Rb polymorphism persists far from any known hybrid zone. We found no differences between the two karyotypic classes in maximum metabolic rate during running (forced activity). However, the Rb heterozygotes showed significantly higher maximum metabolic rate during swimming (forced activity combined with thermal stress). The levels of fluctuating asymmetry (FA) of homozygous and Rb heterozygous shrews were indistinguishable, indicating no effect of chromosomal heterozygosity on developmental stability of shrews. We suggest that selective advantages, such as the higher metabolic performance in activity combined with cold stress, may outweigh the expected negative effects of Rb heterozygosity upon fertility, and help to maintain huge areas of the Rb polymorphism in this species.

Development of a nasal cast model to test medicinal nasal devices.

Bespak, a division of Consort Medical plc, and Queen's University Belfast have developed a viable and unique in-vitro testing capability for nasal drug delivery devices. The aim was to evaluate and optimize current and conceptual drug delivery devices by quantifying the deposition of drug in the various distinct regions of the nasal cavity. The development of this test apparatus employed computed tomography (CT) scan data of the human nasal cavity to construct an accurate representation of the human nasal airways. An investigation of suitable materials and manufacturing technologies was required, together with extensive analytical method development. It is possible for this technique to be further developed in an attempt to create a standardized apparatus based on nasal geometry that can be used to compare accurately deposition from drug delivery devices. This paper presents the issues encountered in the development of this test apparatus, including manufacturing and material limitations, investigation and choice of suitable materials, laboratory testing considerations, and the steps required to validate the analytical process.

Meiotic studies of male common shrews (Sorex araneus L.) from a hybrid zone between chromosome races.

Thirty-three adult male common shrews (Sorex araneus L.) were collected from a hybrid zone between two chromosomal races that differed in Robertsonian metacentrics. Anaphase I nondisjunction frequencies were estimated on the basis of metaphase II counts. RIV and CV complex heterozygotes (four-element rings and five-element chains at meiosis I, respectively) had substantially higher nondisjunction rates than homozygotes and simple Robertsonian heterozygotes. However, at least in the case of RIV-forming hybrids, increased nondisjunction frequency did not result from malsegregation of the heterozygous complex. Extra elements found in hyperploid spreads were most frequently acrocentrics, that could not originate from a fully metacentric multivalent. Complex heterozygotes were also characterized by higher frequencies of univalents observed at diakinesis I. However, univalents did not originate from complex configurations, which were regularly formed with usually one chiasma per chromosome arm. Hence, we suppose that the presence of multivalents in the cell affects pairing and segregation of other elements at meiosis I.

The evolutionary history of the two karyotypic groups of the common shrew, Sorex araneus, in Poland.

Genetic variability within and among two karyotypic groups and five chromosome races of the common shrew (Sorex araneus) in Poland was assayed by sequencing a 1023 bp part of the cytochrome b gene (mtDNA) from 28 individuals. Thirty-four variable positions defined 21 distinct haplotypes with a maximum sequence divergence of 0.88%. No significant differentiation in the cytochrome b gene between Western and Eastern Karyotypic groups was found. Haplotype diversity estimates within the races and groups sampled were high (h = 0.800-0.928), while nucleotide diversity estimates were low (pi = 0.0034-0.0053). The distribution of pairwise nucleotide differences fits well with expectations of a "sudden expansion" model. High haplotype diversity was accompanied by relatively high expected heterozygosity (H(E)) values in nuclear genes (calculated over 47 enzyme loci: H(E) = 0.031 - 0.049), giving no evidence for a recent bottleneck after the process of post-Pleistocene recolonization of Poland by the shrews. Thus, for S. araneus chromosome races in Poland, the data on the cytochrome b gene variability support the hypothesis assuming the Robertsonian fusions having spread into an ancestral acrocentric distribution.

A comparison of spermatogenesis in homozygotes, simple Robertsonian heterozygotes and complex heterozygotes of the common shrew (Sorex araneus L.).

Spermatogenesis was studied in 56 shrews (Sorex araneus L.) from two chromosomal hybrid zones in Poland. The hybrid zones were formed between chromosome races that differed in Robertsonian metacentrics. Shrews were compared in four classes: homozygotes, simple Robertsonian heterozygotes, complex heterozygotes forming four-element rings in meiosis I, and complex heterozygotes forming four- or five-element chains. There was a significant effect of karyotype on the level of germ-cell death and chain-forming complex heterozygotes suffered the greatest germ-cell loss. However, the estimated level of germ-cell death is probably insufficient to influence the fertility of these males.

Synthesis of the unique trisaccharide repeating unit, isolated from lipopolysaccharides Rhizobium leguminosarum bv. trifolii 24, and its analogue.

The synthesis of trisaccharide: 6-d-alpha-L-Talp(1-->2)-alpha-L-Rhap(1-->5)-DHA, and its analogue: 6-d-alpha-L-Talp(1-->2)-beta-L-Rhaf(1-->5)DHA is described. In the first step a disaccharide, composed of 6-d-L-Talp and L-Rhap was obtained. This, in turn, was converted to the corresponding 1-trichloroacetimidate and coupled with DHA alcohol to afford the required trisaccharide. Its analogue was achieved by the conversion of the above disaccharide to the glycosyl bromide, involving the rhamnopyranose ring scission, followed by condensation with DHA in Koenigs-Knorr procedure.

Stereoselective syntheses of the O,N-protected subunits of the tunicamycins.

The synthesis of the title compounds is described, i.e. coupling of the ylide, generated from the iodophosphonium salt of protected N-phthaloyl-D-galactosamine with 2,3-O-isopropylidene D-ribo-aldehyde afforded an undecose in high yield. Hydroboration-oxidation reaction of the olefinic linkage in the undecose led to the desired tunicamine, as the predominant product. After conversion of the latter to a glycosyl acceptor, this was assembled with the fully protected 2-oxyimino-2-deoxy-alpha-D-arabino-hexopyranosyl bromide, leading to a trehalose-type alpha, beta-disaccharide.

Highly stereoselective synthesis of alpha,beta-linked, nonreducing disaccharides related to tunicamycin.

3,4,6-Tri-O-benzoyl-2-(benzoyloxyimino)-2-deoxy-alpha-D-arabino-++ +hexopyranosy l bromide (2) reacts with the O-protected 2-deoxy-2-phthalimido-beta-D-galactosamines 3 and 4 in the presence of silver triflate and sym-collidine at -78 degrees C, to give alpha,beta-(1-->1)-linked disaccharides 6a and 7a with an excellent selectivity. The 2-oxyimino function was stereospecifically converted into a 2-acetamido group by use of the LiBH4-Me3SiCl-THF reductive species, furnishing, after acetylation, the alpha-D-GlcNAc-(1-->1)-beta-D-GalNPhth nonsymmetrical, trehalose type disaccharides 13 and 14 related to tunicamycin (1, part A). Similarly, alpha-D-GlcNAc-(1-->1)-beta-D-GlcNPhth (15) was prepared, starting from 2 and 5. The factors governing the stereoselectivity of the glycosylation reactions were determined.

X-ray and conformational investigation of 6-deoxy-6-C-(1,5-di-O-acetyl-2,3-O- isopropylidene-beta-D-allo-pentofuranos-5-yl)-1,2:3,4-di-O-isopro pylidene-alpha-D-galactopyranose and 6-C-(benzyl 5-deoxy-2,3-O-isopropylidene-beta-D- ribofuranosid-5-yl)-1,2:3,4-di-O-isopropylidene-D-glycero-alpha-D-galac to-hexopyranose.

The structures of the title compounds (2b and 3) have been investigated in the solid state by X-ray methods. The crystals of 2b are monoclinic, space group P2(1), and of 3 orthorhombic, space group P2(1)2(1)2(1). The cell dimensions are: for 2b, a = 9.910(2), b = 11.745(1), c = 11.810(3) A, beta = 97.32(1) degrees; and for 3, a = 6.103(1), b = 15.954(1), c = 28.855(3) A. Both structures were solved by direct methods, and refined by a full-matrix, least-squares procedure giving for 2b, R = 0.0541 (unit weight), and for 3, R = 0.0451 (RW = 0.0445). The galactopyranose rings of 2b and 3 adopted a twist and a mixed twist-screw conformation, respectively. The absolute configuration at C-7 in 2b, as well as at C-6 in 3, was determined to be (R). Relatively strong intermolecular hydrogen bonds were observed in the crystal structure of 3.

The synthesis of two repeating units of Haemophilus influenzae type a capsular antigen.

The repeating units 2-O-beta-D-glucopyranosyl-L-ribitol 4'- and 1-phosphate of Haemophilus influenzae type a capsular antigen have been synthesised by condensation of an alpha-D-glucopyranosyl bromide derivative with 5-O-allyl-1,2,3-tri-O-benzyl-D-ribitol followed by selective deprotection of HO-4' or HO-1, phosphorylation, and removal of the blocking groups.

Crystal and molecular structures of 6-O-acetyl-2,3,4-trideoxy-alpha-DL-glycero-hex-2-enopyranose and 3-O-(6-O-acetyl-2,3,4-trideoxy-alpha-L-glycero-hex-2-enopyranosyl++ +)-1,2 ;5,6-di-O-isopropylidene-alpha-D-glucofuranose.

6-O-acetyl-2,3,4-trideoxy-alpha-DL-glycero-hex-2-enopyranose (1) and 3-O-(6-O-acetyl-2,3,4-trideoxy-alpha-L-glycero-hex-2-enopyranosyl) -1,2;5,6-di-O-isopropylidene-alpha-D-glucofuranose (2) have been investigated by X-ray diffraction methods. Compound 1 crystallises in the monoclinic system, space group P21/a, with cell constants a = 21.123(5), b = 4.439(2), c = 10.085(2) A, and beta = 110.22(2) degrees. Compound 2 crystallises in the orthorhombic system, space group P212121, with cell constants a = 22.110(6), b = 11.651(4), and c = 8.658(3) A. The intensity data were collected in a four-circle automatic diffractometer, with 1488 reflections for 1, and 2151 for 2. The structures were solved by direct methods. The atomic parameters were refined in an anisotropic mode by the full-matrix, least-squares procedure against 1065 and 1884 observed reflections for 1 and 2, respectively, giving R = 0.046 for each compound. The 2-enopyranose rings in 1 and 2 adopt half-chair conformations (H), and that in 2 is markedly deformed. The 1,2-dioxolane ring in 2 has an envelope (E) conformation, whereas the 5,6-dioxolane ring is dynamically disordered and can be represented by a conformational hybrid (E + P). The alpha-D-glucofuranose ring in 2 has a twist conformation (T). The glycoside bond in 2 is characterized by phi and psi torsion angles of 47(2) degrees and 32(2) degrees, respectively.