Effect of anaesthesia on cemented hemiarthroplasty -A multicentre retrospective study (TRON study).

Introduction: This study aimed to investigate the survival rate, postoperative complications, and walking ability in cemented hemiarthroplasty (HA) for displaced femoral neck fractures according to the anaesthesia method.

Methods: We conducted a retrospective study of a multicentre group (the TRON group). Three hundred fifty-eight patients who underwent cemented HA between 2015 and 2019 were selected; 289 patients of ≥75 years of age with no missing data were included.

The potential use of histone deacetylase inhibitors in the treatment of depression.

Numerous preclinical studies demonstrate that changes in gene expression in the brain occur in animal models of depression using exposure to stress, such as social defeat and leaned helplessness, and that repeated administration of antidepressants ameliorates these stress-induced changes in gene expression. These findings suggest that alteration in gene transcription in the central nervous system in response to stress plays an important role in the pathophysiology of depression. Recent advances in epigenetics have led to the realization that chromatin remodeling mediated by histone deacetylase (HDAC) is closely involved in the regulation of gene transcription.

Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder.

Rationale: Given that impairment of fear extinction plays a pivotal role in the pathophysiology of posttraumatic stress disorder (PTSD), drugs that facilitate fear extinction may be useful as novel treatments for PTSD. Histone deacetylase (HDAC) inhibitors have recently been shown to enhance fear extinction in animal studies.

Objectives: Using a single prolonged stress (SPS) paradigm, an animal model of PTSD, we examined whether the HDAC inhibitor vorinostat can facilitate fear extinction in rats, and elucidated the mechanism by which vorinostat enhanced fear extinction, focusing on the N-methyl-D-aspartate (NMDA) receptor signals in the hippocampus.

[Novel therapeutic approach for the treatment of post-traumatic stress disorder (PTSD): facilitating fear extinction].

Pharmacological agents enhancing fear extinction may be promising tools for the treatment of PTSD. Histone acetylation is involved in memory formation, and histone deacetylase (HDAC) inhibitors increase histone acetylation and subsequently enhance fear extinction. In this study, we examined whether vorinostat, an HDAC inhibitor, facilitated fear extinction, using a contextual fear conditioning (FC) paradigm.

Vorinostat, a histone deacetylase inhibitor, facilitates fear extinction and enhances expression of the hippocampal NR2B-containing NMDA receptor gene.

Histone acetylation, which alters the compact chromatin structure and changes the accessibility of DNA to regulatory proteins, is emerging as a fundamental mechanism for regulating gene expression. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance fear extinction. In this study, we examined whether vorinostat, an HDAC inhibitor, facilitates fear extinction, using a contextual fear conditioning (FC) paradigm, in Sprague-Dawley rats.

Epigenetic regulation of BDNF gene in response to stress.

Neuronal plasticity induced by changes in synaptic morphology and function is well known to play a pivotal role in leaning and memory as well as adaptation to stress. It is suggested that these plastic changes are due to orchestration of alterations in gene expression in the brain. Recent advances in molecular biology have provided evidence that epigenetic mechanisms, such as DNA methylation and histone modification, are crucial to gene transcription in the mammalian brain.

[Epigenetic mechanism of depression].

Numerous epigenetic studies have revealed that the acetylated status of histone as well as methylated status of cytosine is closely involved in gene transcription. Preclinical and clinical studies demonstrate that changes in levels of various genes in the brain including BDNF, play a role in the pathophysiology of depression. It is well known that the levels of BDNF mRNA and protein in the rat brain, such as frontal cortex and hippocampus, was decreased in response to stress, but the precise mechanism of stress-induced downregulation of BDNF has yet to be characterized.

Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder.

Because the majority of patients with posttraumatic stress disorder (PTSD) exhibit long-lasting traumatic fear memory, we hypothesize that enhanced fear memory consolidation is closely involved in the pathophysiology of PTSD. Brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are crucial for hippocampal-dependent learning and memory. In particular, differential induction of BDNF gene transcripts mediated by histone acetylation plays a role in the consolidation of fear memory.

Inhibitory effects of 2-amino-3H-phenoxazin-3-one on the melanogenesis of murine B16 melanoma cell line.

Hyperpigmentations are a serious concern addressed by both the medical community and the cosmetic industry through the development of agents that block melanin biosynthesis. In this study, we found that 2-amino-3H-phenoxazin-3-one (APO), isolated from extracts of the edible mushroom Agaricus bisporus Imbach, exhibited potent inhibitory effects on melanogenesis in B16 cells, a murine melanoma cell line. APO inhibited melanin biosynthesis at 1,000 times lower concentrations (IC(50)=1.

Alterations in the hippocampal glycinergic system in an animal model of posttraumatic stress disorder.

Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms, such as enhanced contextual fear in response to trauma-related and trauma-unrelated events. Furthermore, we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanism underlying impaired fear extinction in SPS rats. To clarify the involvement of the hippocampal glycinergic system in impaired fear extinction in SPS rats, we measured the time course of changes in the duration of freezing and the hippocampal levels of Gly-T1 mRNA using contextual fear conditioning (FC) and extinction training.

Single prolonged stress: toward an animal model of posttraumatic stress disorder.

Although selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in decreasing posttraumatic stress disorder (PTSD) symptoms, a subgroup of PTSD patients remain chronically symptomatic and maintain conditioned fear responses to traumatic stimuli. In this context, the establishment of an appropriate animal model of PTSD is necessary to promote better understanding of the mechanisms of the disorder and to facilitate the development of more effective therapeutic alternatives to SSRIs. Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD.

[A novel therapeutic approach for the treatment of post-traumatic stress disorder (PTSD): enhancing the impaired extinction of fear memory].

Although the impaired extinction of traumatic memory is one of the hallmark symptoms of PTSD, the underlying mechanisms of impaired extinction are unclear and effective pharmacological interventions have not yet been developed. In this study, using rats subjected to single prolonged stress (SPS), an animal model of PTSD, we examined (a) the ability of SPS to impair fear extinction, (b) whether D-cycloserine (DCS) can alleviate impaired fear extinction in SPS rats, and (c) the effect of SPS and/or DCS on the levels of N-methyl-D-aspartate (NMDA) receptor subunit mRNAs in the rat hippocampus during extinction training. SPS rats exhibited impaired fear extinction in the contextual fear test, which was alleviated by the repeated administration of DCS.

Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.

It is known that the early environment affects the mental development of rodent and human offspring. However, it is not known specifically whether a postpartum depressive state influences the depressive state in offspring. Using learned helplessness (LH) in rats as an animal model of depression, we examined the influence of maternal postpartum LH on responses to the LH test of offspring.

Creation of interferon-alpha8 mutants with amino acid substitutions against interferon-alpha receptor-2 binding sites using phage display system and evaluation of their biologic properties.

In this study, we describe the creation of three interferon-alpha (IFN-alpha)8 mutants with markedly higher antiviral and antiproliferative activities in comparison with those of the wild-type (wt)IFN-alpha8, wtIFN-alpha2, and IFN-con1 using a phage display system. Sequence analysis showed that three out of the six hot-spot amino acid residues of wtIFN-alpha8 known to be important for the interaction with the IFN-alpha receptor-2 (IFNAR-2)-binding sites were substituted to other amino acids and the others remained. Although affinity analysis revealed that the dissociation constant (K(D)) of IFN-alpha8 mutants was almost the same with that of wtIFN-alpha8, furthermore, the rates of association (k(a)) and dissociation (k(d)) were relatively lower.

Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one.

Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.

Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus.

Decreased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus are implicated in the pathophysiology of major depression, although the mechanism has yet to be characterized. Epigenetic studies revealed that DNA methylation and histone modifications at the promoter of exons of the BDNF gene are the pivotal factors in the regulation of BDNF transcription. Histone acetylation regulates gene transcription through chromatin remodelling.

Effects of single prolonged stress and D-cycloserine on contextual fear extinction and hippocampal NMDA receptor expression in a rat model of PTSD.

Although the impaired extinction of traumatic memory is one of the hallmark symptoms of posttraumatic stress disorder (PTSD), the underlying mechanisms of impaired extinction are unclear and effective pharmacological interventions have not yet been developed. Single prolonged stress (SPS) has been proposed as an animal model of PTSD, since rats subjected to SPS (SPS rats) show enhanced negative feedback of the HPA axis and increased contextual fear, which are characteristics similar to those observed in patients with PTSD. In this study, using SPS rats, we examined (a) the ability of SPS to impair fear extinction, (b) whether D-cycloserine (DCS) can alleviate impaired fear extinction in SPS rats, and (c) the effect of SPS and/or DCS on the levels of N-methyl-D-aspartate (NMDA) receptor subunit mRNAs in the rat hippocampus during extinction training.

The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2.

Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8.

Importance of early lighting conditions in maternal care by dam as well as anxiety and memory later in life of offspring.

Rodent studies have revealed that the early rearing environment plays an important role in the development of stress vulnerability, memory and cognition. Although early lighting conditions (ELC) are involved in these neuronal developments through both maternal and offspring behavior, their influence has not been fully elucidated. Thus, by using Sprague-Dawley rats, we examined whether ELC affected maternal care by the dam and the subsequent neurodevelopment of the offspring.

Role of p53 in the inhibitory effects of interferon-alpha subtypes on proliferation of hepatocellular carcinoma cells.

While interferon-alpha (IFN-alpha) subtypes share a common specific receptor composed of two subunits, interferon-alpha receptor (IFNAR)-1 and IFNAR-2, their subtype activities are exhibited via several intracellular signaling pathways and thus subsequently show different biological effects. Anti-proliferative effects of single treatment with IFN-alpha subtypes or 5-fluorouracil (FU), and of combined treatment with each IFN-alpha subtype and 5-FU were examined on three hepatocellular carcinoma cell lines, HepG2, HLE and PLC/PRF/5. HepG2 and PLC/PRF/5 cells were susceptible to the combination treatment, but HLE cells were not.

Glycoform analysis of Japanese cedar pollen allergen, Cry j 1.

In our previous study (Y. Kimura et al., Biosci.

Effects of interferon-alpha subtypes on the TH1/TH2 balance in peripheral blood mononuclear cells from patients with hepatitis virus infection-associated liver disorders.

Interferon-alpha (IFN-alpha) has recently been shown to modulate in vitro T helper (Th) 1-driven responses in the peripheral blood mononuclear cells (PBMC) of patients with hepatitis B virus or C virus infection. In this study, we examined the in vitro effects of IFN-alpha subtypes (IFN-alpha1, -alpha2, -alpha5, -alpha8, and -alpha10) on the Th1/Th2 balance in PBMC obtained from patients with hepatitis virus infection-associated liver disorders and chronic hepatitis (CH), in comparison with the effect on healthy control volunteer PBMC. The Th1-type cell percentages and Th1/Th2 ratios were significantly higher in the PBMC of patients when compared with controls both before and after cultivation in vitro, with the IFN-alpha subtypes.

Correlation Between Interferon Alpha Receptor Protein Expression and Sensitivity to Interferon Alpha Subtypes in Human Renal Carcinoma Cell Lines.

Background: We have previously characterized the antitumor activities and immunological properties of interferon-alpha (IFN-α) subtypes on renal cell carcinoma (RCC). However, the mechanism responsible for the different biologic activities among the IFN-α subtypes is still unclear. To explain the different cellular sensitivities to IFN-α subtypes, detailed expression of the interferon-alpha receptor (IFNAR)-1 and IFNAR-2 subunits on different RCC cell lines was examined and compared with sensitivity of the cell lines to the IFN-α subtypes.