These studies were undertaken to determine how lysyl oxidase (LOX) and lysyl oxidase like-1 (LOXL) enzymes are targeted to their substrates in the extracellular matrix. Full-length LOX/LOXL and ...constructs containing just the pro-regions of each enzyme localized to elastic fibers when expressed in cultured cells. However, the LOXL catalytic domain without the pro-region was secreted into the medium but did not associate with matrix. Ligand blot and mammalian two-hybrid assays confirmed an interaction between tropoelastin and the pro-regions of both LOX and LOXL. Immunofluorescence studies localized both enzymes to elastin at the earliest stages of elastic fiber assembly. Our results showed that the pro-regions of LOX and LOXL play a significant role in directing the deposition of both enzymes onto elastic fibers by mediating interactions with tropoelastin. These findings confirmed that an important element of substrate recognition lies in the pro-domain region of the molecule and that the pro-form of the enzyme is what initially interacts with the matrix substrate. These results have raised the interesting possibility that sequence differences between the pro-domain of LOX and LOXL account for some of the functional differences observed for the two enzymes.
BACKGROUND Cryopreservation of semen should be offered to adults before gonadotoxic treatment. However, the experience with semen collection in adolescents is still limited. The objective of this ...study was to evaluate potential correlates of successful semen sampling in adolescents. METHODS A total of 86 boys (aged 12.2–17.9 years), referred for cryopreservation of semen prior to gonadotoxic treatment were included. Age, testicular volume, diagnosis and reproductive hormones were evaluated as correlates of successful semen collection. RESULTS Median sperm concentration was 9.6 (range 0–284) million/ml. Of the 86 included boys, 76 (88.4%) had spermatozoa in their ejaculate. Of the 76 patients for whom a semen sample was obtained, 71 (93.4%) had motile spermatozoa eligible for cryopreservation. Of the 86 boys, 74 produced a semen sample by masturbation, whereas semen samples were obtained from 12 patients by penile vibration or electroejaculation. The youngest patient with an ejaculate containing motile spermatozoa was 12.2 years old, and the smallest testicular volumes in boys associated with motile spermatozoa in the ejaculate were 6–7 ml. Testicular volume correlated with sperm concentration (R = 0.283, P = 0.046), and the percentage of motile spermatozoa (R = 0.410, P = 0.003). Chronological age, but not reproductive hormones, also correlated with sperm concentration (R = 0.25, P = 0.049). CONCLUSIONS Semen was successfully collected and cryopreserved in 71 out of 86 boys and adolescents. Testicular volume, but not age or reproductive hormone levels, was indicative of successful semen collection. Regardless of their age, adolescent boys with testicular volumes of more than 5 ml should be offered semen banking prior to gonadotoxic treatment or other procedures that could potentially damage future fertility.
Several reports claim that the enzyme cytochrome c oxidase (CCO) is the primary absorber for red-to-near-infrared (R-NIR) light in cells and causal for mitochondrial adenosine triphosphate (ATP) ...upregulation, and that pulsed R-NIR light has frequent therapeutic effects, which are superior to those of the continuous wave (CW) mode used in low-level light therapy (LLLT).
Convincing evidence that the absorption of R-NIR photons by CCO is involved in mitochondrial ATP upregulations as well as a coherent explanation for the superiority of the pulsed irradiation mode is presently lacking in the literature.
A comprehensive literature search and rigorous analysis of the data published on the idea that CCO is the primary absorber for R-NIR light, and of the claim that the effectivity of the pulsed irradiation mode can be derived from the absorption of R-NIR photons by CCO, reveal a number of severe inconsistencies.
A systematical analysis covering both the theory that CCO is the primary acceptor for R-NIR light and of its use to interpret differences between the biological effect of pulsed light and CW casts doubt on the general validity of the CCO-based hypothesis. Instead, we are offered a simple and conflict-free model accounting for both ATP upregulation and superiority of the pulsed mode in LLLT, which is in agreement with the results of recent laboratory experiments.
CCO is not the primary acceptor for R-NIR light.
Normal skin ageing is characterised by an alteration of the underlying connective tissue with measurable consequences on global skin biophysical properties. The cutis laxa syndrome, a rare genetic ...disorder, is considered as an accelerated ageing process since patients appear prematurely aged due to alterations of dermal elastic fibres. In the present study, we compared the topography and the biomechanical parameters of normal aged skin with an 17 year old cutis laxa patient. Skin topography analyses were conducted on normal skin at different ages. The results indicate that the skin relief highly changes as a function of ageing. The cutaneous lines change from a relatively isotropic orientation to a highly anisotropic orientation. This reorganisation of the skin relief during the ageing process might be due to a modification of the skin mechanical properties, and particularly to a modification of the dermis mechanical properties. A specific bio-tribometer, based on the indentationtechnique under light load, has been developed to study the biophysical properties of the human skin in vivo through two main parameters: the physico-chemical properties of the skin surface, by measuring the maximum adhesion force between the skin and the bio-tribometer; and the bulk mechanical properties. Our results show that the pull-off force between the skin and the biotribometer as well as the skin Young's modulus decrease with age. In the case of the young cutis laxa patient, the results obtained were similar to those observed for aged individuals. These results are very interesting and encouraging since they would allow the monitoring of the cutis laxa skin in a standardised and non-invasive way to better characterize either the evolution of the disease or the benefit of a treatment.
Display omitted
•A Transition between quasi-elastic behaviour and viscoelastic behaviour in correlation with ageing was observed.•Correlation between skin surface relief and skin mechanical properties with ageing was suggested.•Study of biophysical behaviour of skin from cutis laxa disease.•In vivo comparison from normal skin ageing and skin from cutis laxa was carried out.
Excess of exercise increases the risk of atrial fibrillation Müssigbrodt, A.; Weber, A.; Mandrola, J. ...
Scandinavian journal of medicine & science in sports,
September 2017, 2017-Sep, 2017-09-00, 20170901, Letnik:
27, Številka:
9
Journal Article
Recenzirano
An interesting and still not well‐understood example for old medical wisdom “Sola dosis facit venenum” is the increased prevalence of atrial fibrillation (AF) in athletes. Numerous studies have shown ...a fourfold to eightfold increased risk of AF in athletes compared to the normal population. Analysis of the existing data suggests a dose‐dependent effect of exercise. Moderate exercise seems to have a protective effect and decreases the risk of AF, whereas excessive exercise seems to increase the risk of AF. The described cases illustrate clinical manifestations within the spectrum of AF in elderly athletes, that is, exercise‐induced AF, vagal AF, chronic AF, and atrial flutter. As the arrhythmia worsened quality of life and exercise capacity in all patients, recovery of sinus rhythm was desired in all described cases. As the atrial disease was advanced on different levels, different treatment regimes were applied. Lifestyle modification and temporary anti‐arrhythmic drug therapy could stabilize sinus rhythm in one patient, whereas others needed radiofrequency ablation to achieve a stable sinus rhythm. The patient with the most advanced atrial disease necessitated anti‐arrhythmic drug therapy and another left atrial ablation. All described patients remained in sinus rhythm during the long‐term follow‐up.
▶ The phenotype of human dermal fibroblasts is differently modulated in the ex vivo and in the in vitro ageing models. ▶ Differences in fibroblast phenotype are mainly observed during in vitro ...ageing, independently from donor's age. ▶ Parameters of redox balance are markedly modified with in vitro ageing and changes depend also on donor's age. ▶ Extracellular elastin deposition is dramatically reduced with in vitro ageing and is associated to intracellular accumulation. ▶ Fibulin-5 represents a very sensitive ageing marker and may be also involved in the redox balance.
Several studies have analyzed modulation of gene expression during physiological ageing with interesting, but often contradictory results, depending on the model used. In the present report we compare age-related metabolic and synthetic parameters in human dermal fibroblasts (HDF) isolated from young and old subjects (ex vivo ageing model) and cultured from early up to late cumulative population doublings (CPD) (in vitro ageing model) in order to distinguish changes induced in vivo by the aged environment and maintained in vitro, from those associated with cell senescence and progressive CPD. Results demonstrate that fibroblasts from aged donors, already at early CPD, exhibit an impaired redox balance, highlighting the importance of this parameter during ageing, even in the presence of standard environmental conditions, which are considered optimal for cell growth. By contrast, several proteins, as those related to heat shock response, or involved in endoplasmic reticulum and membrane trafficking, appeared differentially expressed only during in vitro ageing, suggesting that, at high CPD, the whole cell machinery becomes permanently altered. Finally, given the importance of the elastic component for a long-lasting connective tissue structural and functional compliance, this study focuses also on elastin and fibulin-5 synthesis and deposition, demonstrating a close relationship between fibulin-5 and ageing.
Evaporation of liquid drops containing nanospheres resulted in circular deposition patterns. The circularity of the patterns depended on the uniformity of the surface tension on the substrate. By ...employing binary suspensions, containing two differently sized nanospheres, it was possible to modulate the fine structure of such rings. Slow evaporation on mirror-polished substrates resulted in well-ordered distributions, where larger particles self-assembled in dense hexagonal packages, forming apparently an external ring, deposited around the massive inner ring. Deposition started at the air/liquid/solid-contact line. Results could inspire principles for the fabrication of optical devices and may be fruitfully used to design biomaterials with cell-selective properties. A simple model is employed to predict the radial arrangement of nanospheres in rings. Deviations from a standard order (predicted by the model) may be useful to detect biologically active nanoparticles.
We identified previously an up-regulation in lysyl oxidase (LOX) expression,an extracellular matrix remodeling enzyme, in a highly invasive/metastatic human breast cancer cell line, MDA-MB-231, ...compared with MCF-7, a poorly invasive/nonmetastatic breast cancer cell line. In this study, we demonstrate that the mRNA expression of LOX and other LOX family members lysyl oxidase-like (LOXL), LOXL2, LOXL3, and LOXL4 was observed only in breast cancer cells with a highly invasive/metastatic phenotype but not in poorly invasive/nonmetastatic breast cancer cells. LOX and LOXL2 showed the strongest association with invasive potential in both highly invasive/metastatic breast cancer cell lines tested (MDA-MB-231 and Hs578T). To determine whether LOX is directly involved in breast cancer invasion, LOX antisense oligonucleotides were transfected into MDA-MB-231 and Hs578T cells, and found to inhibit invasion through a collagen IV/laminin/gelatin matrix in vitro compared with LOX sense oligonucleotide-treated and untreated controls. In addition, treatment of MDA-MB-231 and Hs578T cells with beta-aminopropionitrile (an irreversible inhibitor of LOX enzymatic activity) decreased invasive activity. Conversely, MCF-7 cells transfected with the murine LOX gene demonstrated a 2-fold increase in invasiveness that was reversible by the addition of beta-aminopropionitrile in a dose-dependent manner. In addition, endogenous LOX mRNA expression was induced when MCF-7 cells were cultured in the presence of fibroblast conditioned medium or conditioned matrix, suggesting a role for stromal fibroblasts in LOX regulation in breast cancer cells. Moreover, the correlation of LOX up-regulation and invasive/metastatic potential was additionally demonstrated in rat prostatic tumor cell lines, and human cutaneous and uveal melanoma cell lines. These results provide substantial new evidence that LOX is involved in cancer cell invasion.
Purpose
Postoperative Ileus (POI) remains an important complication for patients after abdominal surgery with an incidence of 10–27% representing an everyday issue for abdominal surgeons. It accounts ...for patients’ discomfort, increased morbidity, prolonged hospital stays, and a high economic burden. This review outlines the current understanding of POI pathophysiology and focuses on preventive treatments that have proven to be effective or at least show promising effects.
Methods
Pathophysiology and recommendations for POI treatment are summarized on the basis of a selective literature review.
Results
While a lot of therapies have been researched over the past decades, many of them failed to prove successful in meta-analyses. To date, there is no evidence-based treatment once POI has manifested. In the era of enhanced recovery after surgery or fast track regimes, a few approaches show a beneficial effect in preventing POI: multimodal, opioid-sparing analgesia with placement of epidural catheters or transverse abdominis plane block; μ-opioid-receptor antagonists; and goal-directed fluid therapy and in general the use of minimally invasive surgery.
Conclusion
The results of different studies are often contradictory, as a concise definition of POI and reliable surrogate endpoints are still absent. These will be needed to advance POI research and provide clinicians with consistent data to improve the treatment strategies.
Lysyl oxidase is an extracellular enzyme critical for the normal biosynthesis of collagens and elastin. In addition, lysyl oxidase reverts ras-mediated transformation, and lysyl oxidase expression is ...down-regulated in human cancers. Since suramin inhibits growth factor signaling pathways and induces lysyl oxidase in ras-transformed NIH3T3 cells (RS485 cells), we sought to investigate the effects of suramin on the phenotype of transformed cells and the role of lysyl oxidase in mediating these effects. Suramin treatment resulted in a more normal phenotype as judged by growth rate, cell cycle parameters, and morphology. β-aminopropionitrile, the selective inhibitor of lysyl oxidase enzyme activity, was remarkably unable to block suramin-induced reversion. By contrast, ectopic antisense lysyl oxidase demonstrated that lysyl oxidase gene expression mediated phenotypic reversion. Since lysyl oxidase is synthesized as a 50 kDa precursor and processed to a 30 kDa active enzyme and 18 kDa propeptide, the effects of these two products on the transformed phenotype of RS485 cells were then directly assessed in the absence of suramin. Here we report, for the first time, that the lysyl oxidase propeptide, and not the lysyl oxidase enzyme, inhibits ras-dependent transformation as determined by effects on cell proliferation assays, growth in soft agar, and Akt-dependent induction of NF-κB activity. Thus, the lysyl oxidase propeptide, which is released during extracellular proteolytic processing of pro-lysyl oxidase, functions to inhibit ras-dependent cell transformation.
PDF
