Aim: Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear ...element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population.Methods: We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method.Results: Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval CI, 1.20–2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20–3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11–4.82).Conclusion: LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism.
The clinical utility of denosumab for the treatment of glucocorticoid-induced osteoporosis (GIOP) has yet to be established. This study aimed to compare the effects of denosumab on bone mineral ...density (BMD) and bone turnover markers to those of alendronate in patients with GIOP.
A prospective, single-center study of 32 patients (18 men; median age, 66.0 years) with glomerular disease receiving prednisolone (PSL) who were diagnosed as having GIOP and had not received bisphosphonates before was conducted. Participants were randomized to either alendronate (35 mg orally once a week) or denosumab (60 mg subcutaneously once every 6 months), and all subjects received calcitriol. The primary endpoint was the percent change in lumbar spine (LS) BMD at 12 months of treatment.
The demographic and clinical characteristics at baseline were not significantly different between the groups. Denosumab treatment markedly decreased serum levels of t-PINP, BAP, and TRACP-5b at 12 months compared to baseline (-57.4%, p<0.001; -30.9%, p<0.01; -57.7%, p<0.001, respectively). After 12 months of alendronate treatment, serum levels of t-PINP, BAP, and TRACP-5b were also significantly decreased compared to pretreatment (-38.9%, p<0.01; -16.3%, p<0.05; -43.5%, p<0.01, respectively). However, no significant differences in the changes of bone turnover markers were found between the two groups. As for the effects on BMD, denosumab treatment markedly increased LS BMD from 6 months compared to baseline, whereas no significant difference compared to pretreatment was found in the alendronate group during the study period. In the comparison of the two groups, a large increase of LS BMD was found in the denosumab treatment group compared to the alendronate treatment group at 12 months (p<0.05).
In patients with GIOP, denosumab treatment markedly suppressed bone turnover, which led to a significantly greater increase in LS BMD than with alendronate treatment. These results suggest that denosumab is a therapeutic option for the treatment of GIOP.
The common marmoset, Callithrix jacchus, is increasingly being used as the preferred nonhuman primate (NHP) model in biomedical research. Marmosets share several physiological and biological ...similarities with humans, as a Simiiformes species, and their use in research programs advances knowledge in several fields. Their unique characteristics, such as their small size, high fecundity, and rapid growth, offer additional advances in laboratory settings. This article reviews the developments in experimental disease models using marmosets based on our experience at the Central Institute for Experimental Animals (CIEA) in Japan. The development of genetically modified marmoset models using advanced genome editing technology is attracting researchers, particularly in neuroscience-related fields. In parallel, various marmoset models of human diseases induced by surgery or drug administration have contributed to preclinical and translational studies. Among these are models for Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, spinal cord injury models, a model for type 1 diabetes induced by the combination of partial pancreatectomy and streptozotocin administration, and a hepatic fibrosis model induced by thioacetamide. The development of these models has been supported by refinements in veterinary care, such as the careful design of anesthetic protocols and better understanding of pathogenic microorganisms. In the second part of this review, we present a compilation of practices currently in use at CIEA that provide optimal animal care and enable safe experimentation.
Current status of dental metal allergy in Japan Kitagawa, Masae; Murakami, Satoshi; Akashi, Yoshihiko ...
Journal of prosthodontic research,
07/2019, Letnik:
63, Številka:
3
Journal Article
Recenzirano
To assess the current status of patients with dental metal allergies in Japan.
This study analyzed dental metal allergy in 1225 patients (1:3 male to female ratio; average age 53.0 ±16.5 years), ...including 300 who were scheduled to undergo dental implant surgery, between 2006 and 2016. For diagnosis of metal allergy, patch tests using metal allergens were performed. Additionally, when necessary, metal element analysis of dental alloys was performed in the mouths of some patients using an X-ray fluorescence analyzer for those who exhibited positive reactions.
Among 925 patients (i.e., excluding those scheduled to undergo dental implant surgery n=300), nearly one-half (44.0%) exhibited a positive response to any metal element in the patch test. The positivity rates were as follows: nickel (22.5%); palladium (14.8%); and zinc (11.5%). Almost one-half (42.3%) of the patients had diseases associated with metal allergy. Among patients who exhibited a positive reaction to any metal element in the patch test, more than two-thirds (67.9%) had dental alloys containing the positive metal element(s). One-half (55.6%) of the patients who underwent treatment to remove the metal experienced improvement in symptoms. In patients who underwent patch testing as an implant preoperative examination, several (2.7%) exhibited a positive reaction to titanium.
Dental metals, including nickel, palladium and zinc, which are indispensable to dental treatment in Japan, had high positivity rates in patch testing, and one-half of the patients improved following removal of the metal. Additionally, there were several patients with allergy to titanium.
There has been a significant shift in epidemiology and renal outcomes of infection-related glomerulonephritis (IRGN) in recent years. The renal prognosis of IRGN is often poor in adults, especially ...in the elderly and diabetics. We herein report an elderly diabetic patient with IRGN due to streptococcal infection complicated by hemophagocytic syndrome and cytomegalovirus nephritis, which is uncommon among non-transplant patients. Infection control and steroids did not recover the patient's renal function. For elderly IRGN patients with diabetes, a further investigation of the most effective treatment for related renal outcomes is needed.
Acute ischemic stroke is characterized by dynamic changes in metabolism and hemodynamics, which can affect brain temperature. We used proton magnetic resonance (MR) spectroscopy under everyday ...clinical settings to measure brain temperature in seven patients with internal carotid artery occlusion to explore the relationship between lesion temperature and clinical course. Regions of interest were selected in the infarct area and the corresponding contralateral region. Single-voxel MR spectroscopy was performed using the following parameters: 2000-ms repetition time, 144-ms echo time, and 128 excitations. Brain temperature was calculated from the chemical shift between water and
-acetyl aspartate, choline-containing compounds, or creatine phosphate. Within 48 h of onset, compared with the contralateral region temperature, brain temperature in the ischemic lesion was lower in five patients and higher in two patients. Severe brain swelling occurred subsequently in three of the five patients with lower lesion temperatures, but in neither of the two patients with higher lesion temperatures. The use of proton MR spectroscopy to measure brain temperature in patients with internal carotid artery occlusion may predict brain swelling and subsequent motor deficits, allowing for more effective early surgical intervention. Moreover, our methodology allows for MR spectroscopy to be used in everyday clinical settings.
We have investigated the most essential kaonic nucleus “K−pp” as a resonant state of the K¯NN-πΣN- πΛN coupled-channel system using a chiral SU(3)-based K¯N potential. We treat the “K−pp” resonance ...adequately with a fully coupled-channel complex scaling method (full ccCSM). Self-consistency needs to be considered for the energy dependence of the chiral SU(3)-based potential. In the present study, we propose a simple prescription for the treatment of self-consistency, considering the averaged threshold and averaged binding energy of mesons. With this prescription, we have successfully found the self-consistent solutions of the “K−pp” three-body resonance. The results indicate that the “K−pp” system is bound rather shallowly. In particular, when the potential parameters are constrained with the latest K¯N scattering length, the binding energy and half of the mesonic decay width are obtained as 14–50 MeV and 8–19 MeV, respectively.
Objective: The purpose of this study was to report the results of stent-assisted embolization performed at our hospital for acutely ruptured aneurysms.Methods: This study consisted of 19 patients (4 ...men and 15 women) with acutely ruptured wide neck aneurysm who underwent stent-assisted coil embolization in acute stage between December 2016 and October 2020. Stent-assisted embolization in the acute stage was performed for very wide neck ruptured aneurysm only when balloon-assisted embolization was failed or was thought to be impossible. Factors related to poor clinical outcome were examined.Results: There were nine internal carotid artery (ICA) aneurysms, four anterior communicating artery (AcomA) aneurysms, three basilar artery (BA) aneurysms, two vertebral artery (VA) aneurysms and one anterior cerebral artery (ACA) aneurysm. The stents used were one Neuroform EZ and 18 Neuroform Atlas (Stryker). The contrast of the bleb disappeared in all cases with obvious bleb. Complete obliteration was achieved in two cases, neck remnant was in ten, and body filling was in seven. Both of the complete obliteration cases developed thrombotic complications. Modified Rankin score of 0–2 was observed in eight patients (good clinical outcome), whereas that of 4–6 was observed in 11 patients (poor clinical outcome). Several factors possibly affected to poor clinical outcome were examined and only age over 80 years was statically different. Complications related to procedure occurred in five patients; two cases of in-stent thrombosis, one case each of MCA perforation, stent occlusion, and coil fracture.Conclusion: Stent-assisted coil embolization using Neuroform EZ and Neuroform Atlas could be considered as an emergency treatment for acutely ruptured cerebral aneurysms with very wide neck. It is rarely indicated in patients with age over 80 years.
Acetaldehyde is the major toxic metabolite of alcohol (ethanol) and enhances fibrosis of the liver through hepatic stellate cells. Additionally, alcohol administration causes the accumulation of ...reactive oxygen species (ROS), which induce hepatocyte injury-mediated lipid peroxidation. Iso-α-acids, called isohumulones, are bitter acids in beer. The purpose of this study was to investigate the protective effects of iso-α-acids against alcoholic liver injury in hepatocytes in mice. C57BL/6N mice were fed diets containing isomerized hop extract, which mainly consists of iso-α-acids. After 7 days of feeding, acetaldehyde was administered by a single intraperitoneal injection. The acetaldehyde-induced increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were suppressed by iso-α-acids intake. Hepatic gene expression analyses showed the upregulation of detoxifying enzyme genes, glutathione-S-transferase (GST) and aldehyde dehydrogenase (ALDH). In vitro, iso-α-acids upregulated the enzymatic activities of GST and ALDH and induced the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nfe2l2; Nrf2), a master regulator of antioxidant and detoxifying systems. These results suggest that iso-α-acid intake prevents acetaldehyde-induced liver injury by reducing oxidative stress via Nrf2-mediated gene expression.
To compare pathologic changes in photoreceptors in eyes with resolved central serous chorioretinopathy (CSC) seen on high-resolution images obtained by adaptive optics scanning laser ophthalmoscopy ...(AO SLO) with visual acuity (VA) and findings on spectral-domain optical coherence tomography (SD OCT).
Observational case series.
Forty-five eyes of 38 patients with resolved CSC and 20 normal eyes of 20 volunteer subjects.
All patients underwent a full ophthalmologic examination, SD OCT, and imaging with an original prototype AO SLO system fabricated using liquid crystal-on-silicon technology.
Cone mosaic patterns and cone density on AO SLO images and VA in eyes with CSC.
In normal eyes, AO SLO images showed a regular photoreceptor mosaic pattern and average cone densities 0.2, 0.5, and 1.0 mm from the central fovea of 67,900, 33,320, and 14,450 cones/mm(2). In eyes with CSC, cone densities were significantly lower at each distance from the central fovea (P = 0.009 at 0.2 mm, P = 0.007 at 0.5 mm, and P = 0.004 at 1.0 mm), and 2 distinct cone mosaic patterns were seen. Group 1 CSC eyes had regular cone mosaic patterns with small dark regions. Group 2 CSC eyes had irregular mosaic patterns with large dark regions. Compared with group 1, group 2 had significantly lower average cone density and worse average logarithm of the minimum angle of resolution (logMAR) VA (P<0.001). Mean cone density in eyes with disruptions in the photoreceptor inner and outer segment (IS/OS) junction or in the intermediate line on SD OCT images was significantly lower than that in eyes with an intact IS/OS junction or intermediate line (P<0.001 for both). Cone density 0.2 mm from the central fovea correlated with logMAR VA and mean foveal thickness (1-mm diameter area) measured on SD OCT images (P<0.001 for both).
Adaptive optics SLO images showed abnormal cone mosaic patterns and reduced cone densities in eyes with resolved CSC, and these abnormalities were associated with VA loss, suggesting that AO SLO is a useful means to detect and measure cone abnormalities associated with VA loss in these eyes.