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Purpose: Aim of this study was to compare the reconstruction of radiological sagittal spinopelvic parameters between lordotic (10°) and normal cages (0°) after dorsal lumbar spondylodesis., Methods: This retrospective monocentric study included patients who received dorsal lumbar spondylodesis between January 2014 and December 2018. Inclusion criteria were degenerative lumbar diseases and mono- or bi-segmental fusions in the middle and lower lumbar region. Exclusion criteria were long-distance fusions (3 segments and more) and infectious and tumour-related diseases. The sagittal spinopelvine parameters (lumbar lordosis, segmental lordosis, sacral slope, pelvic incidence, and pelvic tilt) were measured pre- and post-operatively by two examiners at two different times. The patients were divided into 2 groups (group 1: lordotic cage, group 2: normal cage)., Results: One hundred thirty-eight patients (77 female, 61 male) with an average age of 66.6 ± 11.2 years (min.: 26, max.: 90) were included in the study based on the inclusion criteria. Ninety-two patients (66.7%) received 0° cages and 46 (33.3%) lordotic cages (10°). Segmental lordosis was increased by 4.2° on average in group 1 and by 6.5° in group 2 (p = 0.074). Average lumbar lordosis was increased by 2.1° in group 1 and by 0.6° in group 2 (p = 0.378). There was no significant difference in the correction of sagittal spinopelvic parameters. Inter- and inter-class reliability was between 0.887 and 0.956., Conclusion: According to the results of our study, no advantages regarding sagittal radiological parameters for the implantation of a lordotic cage could be demonstrated.

Myomesin is a 185-kDa protein located in the M-band of striated muscle where it interacts with myosin and titin, possibly connecting thick filaments with the third filament system. By using expression of epitope-tagged myomesin fragments in cultured cardiomyocytes and biochemical binding assays, we could demonstrate that the M-band targeting activity and the myosin-binding site are located in different domains of the molecule. An N-terminal immunoglobulin-like domain is sufficient for targeting to the M-band, but solid-phase overlay assays between individual N-terminal domains and the thick filament protein myosin revealed that the unique head domain contains the myosin-binding site. When expressed in cardiomyocytes, the head domains of rat and chicken myomesin showed species-specific differences in their incorporation pattern. The head domain of rat myomesin localized to a central area within the A-band, whereas the head domain of chicken myomesin was diffusely distributed in the cytoplasm. We therefore conclude that the head domain of myomesin binds to myosin but that this affinity is not sufficient for the restriction of the domain to the M-band in vivo. Instead, the neighboring immunoglobulin-like domain is essential for the precise incorporation of myomesin into the M-band, possibly because of interaction with a yet unknown protein of the sarcomere.

We investigated the assembly of the first sarcomeres in chicken embryos by confocal microscopy of immunofluorescently stained whole mount rudiments of early chicken hearts isolated around the onset of beating. In embryos with merely 9 somites, myomesin was found to be present in a cross striated pattern, indicating that myomesin is expressed rather early during development. RNA studies confirmed these findings and RT-PCR revealed the presence of myomesin mRNA already in the 7 somite embryo. The expression of myomesin mRNA coding for the skeletal isoform preceded the heart specific transcript. In the adult heart, however, only the heart isoform was detectable. The interaction of myomesin domains with the sarcomere was investigated by transfection of epitope tagged constructs into cultured cardiomyocytes. The second domain of myomesin, an immunoglobulin-like domain, was found to specifically bind to the M-band region of chicken cardiomyocytes. All constructs containing this domain also showed M-band localization. Additionally, constructs consisting of either the second domain of myomesin or the myosin light chain isoform MLC 3f fused to the green fluorescent protein (eGFP) were expressed in rat cardiomyocytes and were found to be distributed in the same manner as the expression constructs tagged only with the much shorter VSV epitope. Transfected cells did not show any alteration in beating activity and no alteration of myofibrillar structure, as judged by simultaneous staining for the Z-disc protein alpha-actinin and other sarcomeric markers. Apparently, the addition of eGFP did not disturb the assembly properties or the function of the two proteins and therefore allowed the easy visualization of assembly and contraction processes directly in the living cardiomyocyte.

Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrations of STDHF were selected on the basis of a phase diagram generated by a dynamic laser light-scattering technique to ensure that the mixture was above the critical micellar concentrations. Compared to a 50-micrograms subcutaneous injection, the nasal spray formulation without STDHF had a mean relative bioavailability of 17.9%. For nasal formulations containing 3 and 1.65% (w/v) of STDHF, the bioavailability increased to 29.0 and 25.7%, respectively. The enhancement of nasal absorption was dependent on the STDHF concentrations as shown by decreasing the amounts to 1.2 and 0.8% (w/v) for tolerability reasons; the bioavailability was reduced to 15.3 and 20.5% in these cases, respectively. The local tolerability of all STDHF-containing sprays was poor, leading to stinging sensations and lacrimation. The poor local tolerability of the octreotide nasal spray containing different concentrations of STDHF required for effective nasal absorption enhancement appears to be impractical for further clinical development. These findings clearly stress the necessity to investigate tolerability and safety issues of new drug delivery systems in early developmental phases.

Isolated, rod-shaped adult rat cardiomyocytes (ARC) were kept in long-term cell cultures and the changes of the cardiomyocyte structure were investigated by confocal microscopy. The cells round up and make contact with the substrate by very flat, foot-like structures. After prolonged culture the amorphous cells regenerate a cardiomyocyte-like cytoarchitecture and myofibrils reemerge. In the perinuclear region myofibrils form continuously while in other cells discontinuous myofibrillogenesis was observed, where short sarcomeric segments occur all over the cytoplasmic space. During the regeneration of myofibrils certain proteins like a smooth muscle actin sort to non sarcomeric region, while myomesin or heart C-protein localize on myofibrils with high specificity. This culture system combined with method of epitope-tagging of contractile proteins are ideally suited to monitor the intracellular localization sites of exogenously introduced constructs to different cytoskeletal, since ARC exhibit at the same time stress fiber-like filaments (SFLF) and nascent myofibrils. The molecular properties of the different members of the myosin light chain isoprotein family were investigated by transfection experiments using epitope-tagged myosin light chain (MLC) cDNA. The sorting of the different types of MLC was shown to be isoprotein specific and with chimeric constructs it was shown that the isoprotein-specific incorporation into myofibrils was dependent on the presence of the middle domain of MLC-1f/3f. These MLC isoproteins can be arranged into a sequence of increasing affinity to myofibrils. A hierarchical order of myofibrillar assembly is postulated based on the association affinity. Similar experiments with constructs containing alpha-cardiac, alpha-smooth muscle and gamma-cytoplasmic actins have shown that expression of epitope-tagged actins in ARC result in different epitope staining patterns. While the alpha-cardiac actin showed a marked preference for sarcomeres, the alpha-smooth muscle isoproteins had an intermediate specificity and could either be preferentially incorporated into stress fiber-like filaments (SFLF) and in some cells to a lesser extent into myofibrils as well. Most striking results were obtained with gamma-cytoplasmic actin carrying a 5 or 11-mer epitope. This actin gave rise to large cells, induced the formation of filopodia filled with the transfected actin and depletion of the transfected actin from the perinuclear myofibrillar region.