Expression Profiles of Immune Cells after Propofol or Sevoflurane Anesthesia for Colorectal Cancer Surgery: A Prospective Double-blind Randomized Trial.

BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ± 11.6% vs. 21.3 ± 10.8% before anesthesia and after 1 and 24 h after anesthesia, respectively; difference [95% CI], -0.3 [-4.3 to 3.6], -2.8 [-6.8 to 1.1], and -2.6 [-6.2 to 1.0]; P = 0.863, P = 0.136, and P = 0.151 before anesthesia and after 1 and 24 h, respectively). The fractions of circulating type 1 and type 17 helper T cells, cytotoxic T cells, and CD39+ and CD73+ circulating regulatory T cells were not significantly different between the two groups. The neutrophil to lymphocyte ratio in both groups remained within the normal range and was not different between the groups. CONCLUSIONS: Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Thoracic infectious spondylitis after surgical treatments of herniated lumbar intervertebral disc.

The postoperative infectious spondylitis has been reported to occur among every 1% to 12%. It is difficult to early diagnose in some cases. If the diagnosis is delayed, it can be a life-threatening condition. We report a 32-year-old male patient with postoperative infectious spondylitis. He had surgical treatments for traumatic intervertebral disc herniations in L3-4 and L4-5. Three weeks after surgery, he complained for fever and paraplegia. Cervicothoracic magnetic resonance imaging showed the collapsed T2 and T3 vertebral body with changes of bone marrow signal intensity. Moreover, it showed anterior and posterior epidural masses causing spinal cord compressions which suggested infectious spondylitis. After the use of antibiotics and surgical decompressions T2-T3, his general conditions were improved and muscle power of lower extremities began to be gradually restored. However, we could not identify the exact organisms that may be the cause of infectious spondylitis. It could be important that the infectious spondylitis, which is presented away from the primary operative level, should be observed in patients with fevers of unknown origin and paraplegia.

Comparison of human first and third trimester placental mesenchymal stem cell.

Placenta mesenchymal stem cells (PMSCs) have the characteristic features of stem cells including renewability in vitro, surface expression, differentiation potency and ability to adhere to the culture surface. PMSCs expressed genes are normally found in the embryonic tissues before the onset of gastrulation, indicating multipotency. However, the stemness can depend on the stages of the placenta from which the cells were isolated. PMSCs were isolated from two different stages of placenta for comparison, that is the first and third trimesters. Both sets had very similar patterns of surface expression as CD44, CD73, CD90 and CD105, and of self renewability in vitro. Expressions of pluripotency-coupled genes were also confirmed in both sets of cells; however, there was a significant difference in the expression levels: fPMSC (mesenchymal stem cells isolated from the first trimester human placenta) being 2-11-fold higher than tPMSC (mesenchymal stem cells isolated from the third trimester human placenta). Possibly due to the difference in the expression levels of the pluripotency-related genes, induction of genes specific to the ectodermal tissues were more prominent in fPMSC than tPMSC after induced differentiation.

Dopaminergic differentiation of neural progenitors derived from placental mesenchymal stem cells in the brains of Parkinson's disease model rats and alleviation of asymmetric rotational behavior.

Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons in the mesencephalic substantia nigra and is accompanied by behavioral abnormalities. Pharmacological administration of L-dihydroxyphenylalanine (l-dopa) improves the abnormalities in the early phase of the illness, but numerous adverse effects hinder long-term administration. Transplantation of fetal mesencephalic tissues has been suggested as an alternative to l-dopa treatment; however, the use of human fetal tissues is controversial. Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation and are thus a promising substitute for fetal tissue for the replacement of diseased tissues or organs. Previously, this group isolated 17 independent MSCs from the first trimester human placenta (termed first trimester placental MSCs, or fPMSCs) and reported their successful in vitro differentiation into fPMSC-derived neural progenitors (fPMSC-NPs) (Park et al., Placenta 2011; 32:269-276). In the current study, the in vitro-generated fPMSC-NPs were transplanted into the striatum of a rat model of PD to evaluate whether they could undergo terminal differentiation and mediate behavioral recovery. As early as 2 weeks after transplantation, a minor but significant amelioration of rotational asymmetry was observed, and near-normal motor function was achieved at 24weeks. Immunohistochemical and positron emission tomography (PET) analyses provided experimental evidence for the dopaminergic differentiation of the transplanted progenitors. These results show that in vitro-generated fPMSC-NPs are capable of terminal differentiation in vivo and can attenuate motor defects associated with PD. Hence, the placenta is an auspicious source of stem cells for the therapeutic treatment of neurological disorders.

Use of videofluoroscopic swallowing study in patients with aspiration pneumonia.

OBJECTIVE: To investigate the clinical characteristics of dysphagic elderly Korean patients diagnosed with aspiration pneumonia as well as to examine the necessity of performing a videofluoroscopic swallowing study (VFSS) in order to confirm the presence of dysphagia in such patients. METHOD: The medical records of dysphagic elderly Korean subjects diagnosed with aspiration pneumonia were retrospectively reviewed for demographic and clinical characteristics as well as for VFSS findings. RESULTS: In total, medical records of 105 elderly patients (81 men and 24 women) were reviewed in this study. Of the 105 patients, 82.9% (n=87) were admitted via the emergency department, and 41.0% (n=43) were confined to a bed. Eighty percent (n=84) of the 105 patients were diagnosed with brain disorders, and 68.6% (n=72) involved more than one systemic disease, such as diabetes mellitus, cancers, chronic cardiopulmonary disorders, chronic renal disorders, and chronic liver disorders. Only 66.7% (n=70) of the 105 patients underwent VFSS, all of which showed abnormal findings during the oral or pharyngeal phase, or both. CONCLUSION: In this study, among 105 dysphagic elderly patients with aspiration pneumonia, only 66.7% (n=70) underwent VFSS in order to confirm the presence of dysphagia. As observed in this study, the evaluation of dysphagia is essential in order to consider elderly patients with aspiration pneumonia, particularly in patients with poor functional status, brain disorders, or more than one systemic disease. A greater awareness of dysphagia in the elderly, as well as the diagnostic procedures thereof, particularly VFSS, is needed among medical professionals in Korea.

Glutathione peroxidase activity modulates recovery in the injured immature brain.

OBJECTIVE: Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain. METHODS: Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments. RESULTS: In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group. INTERPRETATION: Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate.

Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBI-- inflammation, oxidative injury, and iron-induced damage-- and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.