Aging leads to inferior Achilles tendon mechanics and altered ankle function in rodents

Spontaneous rupture of the Achilles tendon is increasingly common in the middle aged population. However, the cause for the particularly high incidence of injury in this age group is not well understood. Therefore, the objective of this study was to identify age-specific differences in the Achilles tendon-muscle complex using an animal model. Functional measures were performed in vivo and tissues were harvested following euthanasia for mechanical, structural, and histological analysis from young, middle aged, and old rats. Numerous alterations in tendon properties were detected across age groups, including inferior material properties (maximum stress, modulus) with increasing age. Differences in function were also observed, as older animals exhibited increased ankle joint passive stiffness and decreased propulsion force during locomotion. Macroscale differences in tendon organization were not observed, although cell density and nuclear shape did vary between age groups. Muscle fiber size and type distribution were not notably affected by age, indicating that other factors may be more responsible for age-specific Achilles tendon rupture rates. This study improves our understanding of the role of aging in Achilles tendon biomechanics and ankle function, and helps provide a potential explanation for the disparate incidence of Achilles tendon ruptures in varying age groups.     

It’s a knockout: CCN3 suppresses neointimal thickening

The role of CCN proteins in vivo is only just becoming understood. A prototypical member of the CCN family, CCN3 suppresses proliferation. In a study in press, Shimoyama and colleagues show that mice lacking CCN3 have a hyperproliferative response to vascular injury. These data, along with other recent observations, suggest that CCN3 may represent a novel therapy for hyperproliferative diseases.     

Reutilisation of tritiated thymidine in studies of regenerating skeletal muscle

Summary Two different aspects of tritiated thymidine (³H-Tdr) reutilisation in skeletal muscle were examined. Injection of a high dose (7 Ci/g) of ³H-Tdr into mice prior to crush injury of skeletal muscle resulted in heavy labelling (grain counts) of myotube nuclei 9 d later. In contrast, myotube nuclei were essentially unlabelled when a low dose (1 Ci/g) of ³H-Tdr was injected at similar times with respect to injury. It was concluded that labelling seen after the high dose was due to reutilisation of ³H-Tdr. (Such ³H-Tdr reutilisation can account for the results of Sloper et al. (1970) which previously supported the concept of a circulating muscle precursor cell.) When replicating muscle precursors were labelled directly with ³H-Tdr 48 h after injury, the percentages of labelled myotube nuclei and the distribution of nuclear grain counts were similar with either high or low dose.We also investigated whether the light labelling seen in regenerated myotube nuclei after 9 d, when ³H-Tdr had been injected before the onset of myogenesis (as found by McGeachie and Grounds 1987), was due to ³H-Tdr reutilisation or, alternatively, to proliferation of local cells in the wound which subsequently gave rise to muscle precursors. Labelling of myotube nuclei was compared in mice injected with ³H-Tdr either 2 h before, or 2 h after injury. In another experiment, mice were injected 12 h after injury and lesions sampled 1, 12 or 36 h later, to see whether local cells were replicating 12 h after injury, and what labelled cells subsequently entered to wound. No difference was found in myotube labelling between mice injected before or after injury, and no cells replicating locally in the wound at 12 h after injury were observed. The results clearly show that the light labelling was due to ³H-Tdr reutilisation.     

Cellular differences in the regeneration of murine skeletal muscle: a quantitative histological study in SJL/J and BALB/c mice

Summary Skeletal muscle regeneration in SJL/J and BALB/c mice subjected to identical crush injuries is markedly different: in SJL/J mice myotubes almost completely replace damaged myofibres, whereas BALB/c mice develop fibrotic scar tissue and few myotubes. To determine the cellular changes which contribute to these differential responses to injury, samples of crushed tibialis anterior muscles taken from SJL/J and BALB/c mice between 1 and 10 days after injury were analysed by light and electron microscopy, and by autoradiography. Longitudinal muscle sections revealed about a 2-fold greater total mononuclear cell density in SJL/J than BALB/c mice at 2 to 3 days after injury. Electron micrographs identified a similar proportion of cell types at 3 days after injury. Autoradiographic studies showed that the proportions of replicating mononuclear cells in both strains were similar: therefore greater absolute numbers of cells (including muscle precursors and macrophages) were proliferating in SJL/J muscle. Removal of necrotic muscle debris in SJL/J mice was rapid and extensive, and by 6 to 8 days multinucleated myotubes occupied a large part of the lesion. By contrast, phagocytosis was less effective in BALB/c mice, myotube formation was minimal, and fibrotic tissue conspicuous. These data indicate that the increased mononuclear cell density, more efficient removal of necrotic muscle, together with a greater capacity for myotube formation in SJL/J mice, contribute to the more successful muscle regeneration seen after injury.     

Acute and Prolonged Alterations in Brain Free Magnesium Following Fluid Percussion-Induced Brain Trauma in Rats

Abstract: Several studies have reported declines in brain total and free magnesium concentration after a traumatic insult to the CNS. Although the evidence suggests that this magnesium decline is associated with eventual neurologic outcome after trauma, the duration of free magnesium decline and its impact on related bioenergetic variables are relatively unknown. The present study has therefore used phosphorus magnetic resonance spectroscopy to determine the length of time that free magnesium remains suppressed after traumatic brain injury in rats. Immediately after the traumatic event, brain intracellular free magnesium declined to <60% of preinjury values and remained significantly depressed (50 ± 8%; p < 0.001) for 5 days before recovering to preinjury levels by day 8. Cytosolic phosphorylation ratio and mitochondrial oxidative capacity also significantly decreased ( p = 0.008) and increased ( p = 0.002), respectively, after trauma. However, unlike the time of maximum magnesium change, the maximum changes in these bioenergetic variables occurred at 16–24 h after trauma and thereafter remained stable until after the magnesium had recovered. We conclude that free magnesium decline after trauma precedes changes in bioenergetic variables. Furthermore, therapies targeted at reestablishing magnesium homeostasis after trauma may require administration over a 1-week period.     

Modulation of gap junction-mediated intercellular communication in embryonic chick mesenchyme during tissue remodeling in vitro

Gap junction-mediated intercellular communication was analyzed in a model system in which tissue necrosis and remodeling could be modulated. This in vitro system, previously used for analysis of epithelial-mesenchymal tissue interaction, was modified to permit analysis of the presence and extent of intercellular communition by monitoring intercellular transfer of the micro-injected fluorescent dye, Lucifer Yellow. Light and transmission electronmicroscopy were employed to correlate the presence and degree of gap junctional communication (coupling) with tissue morphology. Digital image analysis was used to determine cell density and mitotic indices within the outgrowths of explants. Our results indicated that cell communication in outgrowths adjacent to necrotic foci within an explant was minimal or absent. Cell-coupling in outgrowths adjacent to a compartment of viable mesenchyme was significantly higher-equivalent to unseparated control cultures. A time-course study demonstrated correlation of increased levels of cell-coupling in outgrowths with the level of tissue remodeling within an explant. Our conclusions from these studies are that embryonic mesenchymal cell populations may be selectively uncoupled as a result of alterations in the microenvironment produced by a proximate impaired cell population. It is proposed that endogenous factors in the microenvironment (wound signals), emanating from impaired cell populations, regulate gap junction-mediated intercellular communication in adjacent viable tissue. Normal, unimpaired populations of cells surrounding an area of injury are thereby isolated from the effects of a potentially toxic environment. This could serve as a protective function in development and may represent, in a more general sense, part of the repertoire of events associated with tissue repair and remodeling.     

Cerebrospinal Fluid Nitrite/Nitrate Levels in Neurologic Diseases

Abstract: Nitric oxide has been proposed to mediate cytotoxic effects in inflammatory diseases. To investigate the possibility that overproduction of nitric oxide might play a role in the neuropathology of inflammatory and noninflammatory neurological diseases, we compared levels of the markers of nitric oxide, nitrite plus nitrate, in the CSF of controls with those in patients with various neurologic diseases, including Huntington's and Alzheimer's disease, amyotrophic lateral sclerosis, and HIV infection. We found that there were no significant increases in the CSF levels of these nitric oxide metabolites, even in patients infected with HIV or in monkeys infected with poliovirus, both of which have significantly elevated levels of the neurotoxin quinolinic acid and the marker of macrophage activation, neopterin. However, CSF quinolinic acid, neopterin, and nitrite/nitrate levels were significantly increased in a small group of patients with bacterial and viral meningitis.     

Injury and repair in biocide-treated spores of Bacillus subtilis

Abstract Bacillus subtilis NCTC 8236 spores exposed to appropriate concentrations of test biocides (glutaraldehyde, two iodine and two chlorine preparations) were able to repair injury if subsequently held in nutrient broth at 37°C but not in broth at 22°C, sterile filtered water at 4, 22 or 37°C or germination medium at 37°C. Repair appeared to occur primarily during outgrowth and was initiated soonest for iodine-treated spores and latest for glutaraldehyde-treated ones.     

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.     

枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响

摘要 目的：探讨枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎（RA）合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响。方法：纳入2021年8月至2022年8月期间徐州医科大学附属连云港医院诊治的80例RA合并骨质疏松患者。根据随机数字表法将患者分为对照组（雷公藤多苷片联合仙灵骨葆胶囊治疗）和实验组（枸橼酸托法替布片联合仙灵骨葆胶囊治疗）,各为40例。对比两组疗效、炎症细胞因子、骨强度及骨代谢指标,观察两组不良反应发生率。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组治疗后巨噬细胞集落刺激因子（M-CSF）、白细胞介素-1β（IL-1β）、环氧合酶-2（COX-2）低于对照组同期（P<0.05）。实验组治疗后横截面积（CSA）、横截面转动惯量（CSMI）、截面系数（Z）、皮质厚度（CT）高于对照组同期（P<0.05）。实验组治疗后骨钙素N端中分子（N-MID）、总Ⅰ型胶原氨基端延长肽（T-PINP）、骨钙素（BGP）、Ⅰ型胶原羧基端前肽（PICP）高于对照组同期,β-胶原降解产物（β-CTX）低于对照组同期（P<0.05）。两组治疗后腰椎骨密度和股骨颈骨密度较治疗前升高,且实验组高于对照组同期（P<0.05）。两组治疗后血沉（ESR）、C反应蛋白（CRP）、类风湿关节炎患者病情（DAS28）评分下降,且实验组低于对照组同期（P<0.05）。两组不良反应发生率组间对比无统计学差异（P>0.05）。结论：枸橼酸托法替布片联合仙灵骨葆胶囊应用于RA合并骨质疏松患者,可有效调节骨代谢水平,增强骨强度,降低血清炎症细胞因子水平。