The efficacy of surgical treatment on locomotive syndrome and physical function in patients with lumbar spinal canal stenosis

BackgroundLocomotive syndrome is a condition of reduced mobility due to problems with locomotive organs. Although lumbar spinal canal stenosis is one of the major diseases constituting locomotive syndrome, only few studies have focused on the association between the two pathologies. We aimed to investigate the effect of surgery on lumbar spinal canal stenosis with respect to locomotive syndrome using various physical function tests, including locomotive syndrome risk tests, before and after surgery.MethodsClinical data of 101 consecutive patients (male = 46; female = 55; mean age, 69.3 years) who underwent surgery for lumbar spinal canal stenosis at our institute were prospectively collected. Results of physical function tests, including stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale, and the sagittal vertical axis were evaluated before and 1 year after surgery. The association between several parameters and improvement of risk level in locomotive syndrome was evaluated.ResultsIn the total assessment, 93.1% of cases were in stage 2 and 6.9% in stage 1 preoperatively, while 72.4% were in stage 2, 22.4% in stage 1, and 5.2% in stage 0 at 1 year postoperatively. Postoperative improvement in the total assessment was observed in 28.7% of cases. Several physical function tests and sagittal vertical axis showed significant improvement after surgery. On multiple logistic regression analysis, age >75 years (odds ratio = 10.9, confidence interval = 1.09–109) and postoperative sagittal vertical axis >40 mm (odds ratio = 17.8, confidence interval = 1.78–177) were significant risk factors associated with non-improvement in risk level of locomotive syndrome.ConclusionsSurgical treatment for lumbar spinal canal stenosis improved physical function, including locomotive syndrome. Risk factors associated with non-improvement of locomotive syndrome were later-stage elderly and postoperative sagittal balance impairment.     

Organogenesis in deep time: A problem in genomics,development, and paleontology

The fossil record is a unique repository of information on major morphological transitions. Increasingly, developmental, embryological, and functional genomic approaches have also conspired to reveal evolutionary trajectory of phenotypic shifts. Here, we use the vertebrate appendage to demonstrate how these disciplines can mutually reinforce each other to facilitate the generation and testing of hypotheses of morphological evolution. We discuss classical theories on the origins of paired fins, recent data on regulatory modulations of fish fins and tetrapod limbs, and case studies exploring the mechanisms of digit loss in tetrapods. We envision an era of research in which the deep history of morphological evolution can be revealed by integrating fossils of transitional forms with direct experimentation in the laboratory via genome manipulation, thereby shedding light on the relationship between genes, developmental processes, and the evolving phenotype.Paleontologists in recent decades have discovered a host of new taxa that reveal transitional stages in the evolution of birds, whales, mammals, tetrapods, frogs, salamanders, and arthropods (1–9). This pulse of discovery is not an accident, but the result of an elaboration of our ability to identify likely sites for fossil recovery by using increasingly refined phylogenies, stratigraphic maps, and geological records. Likewise, imaging techniques, such as high-energy CT, have opened up old and understudied fossil collections as new vehicles for discovery. With advances in both fieldwork and imaging, the discovery of the phenotypic basis for morphological innovation is at a critical moment in its long history: Novel perspectives on classical questions of anatomical evolution are within our reach.Fossils, when placed in a phylogenetic context, can reveal taxa with novel combinations of characters that could not be predicted by studying extant creatures alone. If we lacked fossil evidence of mammal-like reptiles, for example, then the physiological and morphological similarities of birds and mammals would likely be interpreted as homologies rather than examples of parallel evolution (e.g., the discredited “Haemothermia” clade) (10, 11). In addition to identifying solid taxonomic groupings, these same fossils reveal transitional series in the origin of the mammalian dentition, ear, and cranium (3). Our understanding of numerous other transformations, from the origin of birds to the origin of tetrapods, is seriously limited without the knowledge of extinct stem taxa.A rich fossil record permits us to document robustly supported transformation series in the evolution of an anatomical feature, organ system, or body plan. However, to understand the pattern and process of evolutionary transitions, paleontologists have increasingly turned their attention to development. In recent years, the combination of technologies from developmental biology and abundant genomic resources for a multitude of model and nonmodel organisms has greatly enriched our understanding of the genetic and developmental processes underlying organogenesis. This broad set of tools provides a new framework for testing hypotheses derived from paleontological findings, thereby forming an interdisciplinary research program with comparative genomics as well as genetic manipulation of embryonic development (12–15).Here, we use the evolution and diversification of the vertebrate limb as an exemplar to reveal how discoveries in paleontology can leverage experimental and comparative work in molecular biology, genomics, and embryology. First, we review how fossil analyses of early gnathostomes, coupled with embryological studies, offer the foundation for hypotheses on the origin of paired appendages. Then, we discuss current research on model and nonmodel species that shed light on the origin of digits by comparing gene expression and regulatory mechanisms underlying fin and limb development. Next, we examine recent studies that identify the genetic and developmental basis for digit reduction in tetrapods. Finally, we highlight novel technologies that are enabling biologists to solve century-old evolutionary puzzles with state-of-the-art molecular approaches. The synthesis of modern technology with paleontological findings has been an ongoing topic of interest (16–18). Continued advances in technology now give morphologists an ever-expanding toolkit to test genome function and, ultimately, manipulate genomes in a phylogenetic framework. When these new technologies are coupled with paleontological discovery, new insights into classical questions in evolutionary morphology lie in the offing.     

Cartilage formation by serial passaged cultured chondrocytes in a new scaffold: Hybrid 75:25 poly(L-lactide-ε-caprolactone) sponge

PURPOSE: This study was designed to determine whether multipled chondrocytes immersed in a new scaffold, 75:25 poly(L-lactide-epsilon-caprolactone) sponge coated with type I collagen (75-PLC scaffold), could be used to generate cartilage tissue in vivo and to evaluate the correlation between cartilage generation and the phenotype of the proliferated chondrocytes. MATERIALS AND METHODS: Rat chondrocytes were suspended in 75-PLC scaffold at a density of 1 x 10 7 cells/mL after proliferation in a monolayer for 1 (P1) to 4 passages (P4) and implanted in nude mice for 4 weeks. Cells were characterized by the expression of genes encoding type II collagen, aggrecan, and type I collagen by Northern hybridization, and consequently, the newly formed tissue was evaluated histologically. RESULTS: The expression of aggrecan messenger RNA gradually decreased with the passaged cultures; however, the expression of type I collagen messenger RNA increased with time. The cartilage formations in all specimens were found not only in P1 chondrocytes but also in P2 chondrocytes, although when P3 chondrocytes were grafted, approximately 50% of cartilage formation was still observed up to but not beyond P4. CONCLUSION: It is suggested that cartilage tissue is generated with cultured chondrocytes up to P2 but not beyond P4. Northern blot analysis is useful for the assessment of whether the cells are capable of regeneration.     

New biomarker evidence of oxidative DNA damage in whole saliva from clinically healthy and periodontally diseased individuals

BACKGROUND: There is an increasing body of evidence implicating reactive oxygen species in the pathogenesis of periodontal tissue destruction. 8-Hydroxy-deoxyguanosine (8-OHdG) is one of the most commonly used markers to evaluate oxidative damage in a number of disorders including chronic inflammatory diseases. The aim of the present study was to evaluate 8-OHdG levels in whole saliva of patients with periodontitis and to assess the changes after initial treatment. METHODS: Saliva samples were collected from 78 patients with untreated periodontitis and 17 healthy control subjects. Clinical parameters and levels of 8-OHdG were assessed first to establish a baseline and again after initial periodontal treatment from 15 patients. 8-OHdG levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean value of 8-OHdG in the saliva of periodontally diseased subjects, 4.28 +/- 0.10 ng/ml, was significantly higher (P<0.01) than that of clinically healthy subjects (1.56 +/- 0.10 ng/ml). A significant decrease in salivary 8-OHdG was observed after therapy (P<0.01). CONCLUSION: In the present study, we evaluated for the first time 8-OHdG levels in whole saliva of patients with periodontitis and assessed changes after initial periodontal treatment. Our study indicated that 8-OHdG levels in saliva appear to reflect the status of periodontal health.     

Diagnostic accuracy of ultra-high-b-value 3.0-T diffusion-weighted MR imaging for detection of prostate cancer

PurposeTo investigate the diagnostic accuracy of 3.0-T diffusion-weighted imaging (DWI) for detection of prostate cancer by using different b-values.MethodsSeventy-three patients underwent magnetic resonance imaging (MRI) at 3.0 T. Three MRI sets were reviewed by two radiologists: MRI and DWI (b=500s/mm²) (protocol A), MRI and DWI (b=1000s/mm²) (protocol B), and MRI and DWI (b=2000s/mm²) (protocol C). Areas under the receiver operating characteristic curve (AUCs) were calculated.ResultsThe mean of the AUCs in protocol C was larger than those in protocol A and in protocol B (P<.05).ConclusionDWI (b=2000s/mm²) at 3.0 T can improve the diagnostic accuracy for detection of prostate cancer.     

Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis

Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach as the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R). Circulating ghrelin is produced predominantly in the oxyntic mucosa of stomach. Ghrelin potently stimulates GH release and feeding, and exhibits positive cardiovascular effects, suggesting a possible clinical application. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin in glucose metabolism. Here, we review the physiological role of ghrelin in the regulation of insulin release and glucose metabolism, and a potential therapeutic avenue to treat type 2 diabetes by manipulating ghrelin and/or its signaling. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin in islet β-cells are distinct from those utilized in GH-releasing and/or GHS-R-expressing cells. Ghrelin is expressed in pancreatic islets and released into pancreatic microcirculations. Pharmacological and genetic blockades of islet-derived ghrelin markedly augment glucose-induced insulin release in vitro. In high-fat diet-induced mildly obese mice, ghrelin-deficiency enhances insulin release and prevents impaired glucose tolerance. Thus, manipulation of insulinostatic function of ghrelin — GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand, providing a potential therapeutic application to prevent type 2 diabetes.     

Receptor activator of NF-κB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein

Although extensive studies have done much to clarify the molecular mechanisms of osteoclastogenesis during the last ten years, there may still be unknown molecules associated with osteoclast differentiation. Thus, we used fluorescent differential display to screen for genes whose expression is induced by receptor activator of NF-κB ligand (RANKL), a crucial molecule for osteoclast formation. We identified caveolin-1 (Cav-1) as a RANKL-induced gene. Cav-1 is a major structural protein of caveolae and lipid rafts, cholesterol-enriched microdomains in the plasma membrane (PM). The RANKL-induced Cav-1 was immediately conveyed to lipid rafts. Conversely, expression of flotillin-1 (Flot-1), another scaffolding protein of lipid rafts, was reduced during osteoclastogenesis, indicating conversion of Flot-1-predominant rafts into Cav-1-enriched rafts. However, in vitro osteoclastogenesis of precursor cells from Cav-1-null mice was comparable to that of wild-type mice, while Cav-2 expression in the knockout osteoclasts was maintained. Conversely, Cav-2 gene silencing in Cav-1-null osteoclast precursors using siRNA for Cav-2 increased osteoclast formation, suggesting that the Cav-1/Cav-2 complex may act as a negative regulator for osteoclastogenesis. On the other hand, destruction of lipid rafts by removal of cholesterol from the PM by methyl-ß-cyclodextrin (MCD) treatment caused disordered signal transductions for osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulus. The abnormal signaling was reproduced by deleting exogenous lipoproteins from the culture medium, which also resulted in reduced osteoclast formation. In addition, the deletion caused delayed expression of nuclear factor of activated T cells c1 (NFATc1), and depressed its activation in the cytosol and inhibited its translocation into nuclei. Simultaneously, the deletion reduced the level of FcRγ, a trigger protein for initiating the calcium signaling needed to activate NFATc1, and decreased Cav-1 in lipid rafts. These findings indicate that the molecular mechanisms of osteoclastogenesis are highly dependent on extracellular lipoprotein and the integrity of lipid rafts, and suggest possible involvement of cholesterol.     

Relationship between paraspinal muscle cross-sectional area and relative proprioceptive weighting ratio of older persons with lumbar spondylosis

[Purpose] The purpose of this study was to examine the relationship between the paraspinal muscle cross-sectional area and the relative proprioceptive weighting ratio during local vibratory stimulation of older persons with lumbar spondylosis in an upright position. [Subjects] In all, 74 older persons hospitalized for lumbar spondylosis were included. [Methods] We measured the relative proprioceptive weighting ratio of postural sway using a Wii board while vibratory stimulations of 30, 60, or 240 Hz were applied to the subjects’ paraspinal or gastrocnemius muscles. Back strength, abdominal muscle strength, and erector spinae muscle (L1/L2, L4/L5) and lumbar multifidus (L1/L2, L4/L5) cross-sectional areas were evaluated. [Results] The erector spinae muscle (L1/L2) cross-sectional area was associated with the relative proprioceptive weighting ratio during 60Hz stimulation. [Conclusion] These findings show that the relative proprioceptive weighting ratio compared to the erector spinae muscle (L1/L2) cross-sectional area under 60Hz proprioceptive stimulation might be a good indicator of trunk proprioceptive sensitivity.Key words: Relative proprioceptive weighting ratio, Erector spinae muscle cross-sectional area, Older persons with lumbar spondylosis