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1.
Endocr J ; 71(2): 199-206, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38171884

ABSTRACT

Endometriosis, a common gynecological disorder characterized by the growth of endometrial gland and stroma outside the uterus, causes several symptoms such as dysmenorrhea, hypermenorrhea, and chronic abdominal pain. 17ß estradiol (E2) stimulates the growth of endometriotic lesions. Although estetrol (E4), produced by human fetal liver, is also a natural estrogen, it may have the opposite effects on endometriotic cells. We investigated different effects of E4 and E2 on the invasion and migration of immortalized human endometrial stromal cells (HESCs) and evaluated whether E4 affects the expression of Wiskott-Aldrich syndrome protein (WASP) family member 1 (WASF-1). We measured the invasion of HESCs by a Matrigel chamber assay. Cell migration was measured by wound healing assay and cell tracking analysis. The expression of WASF-1 was confirmed by independent real-time PCR analysis. Transfection of cells with siRNAs was carried out to knock down the expression of WASF-1 in HESCs. E4 significantly inhibited E2-induced invasion and migration of HESCs. WASF-1 was found to be a potential mediator based on metastasis PCR array. WASF-1 was upregulated by E2 and downregulated by E4. Knockdown of WASF-1 inhibited migration. Our results suggest that E4 may inhibit E2-induced growth of endometriotic lesions. Downregulation of WASF-1 is involved in the inhibitory effects of E4 on migration. The use of E4 combined with progestins as combined oral contraceptives may cause endometriotic lesions to regress in women with endometriosis.


Subject(s)
Endometriosis , Estetrol , Humans , Female , Estetrol/metabolism , Estetrol/pharmacology , Endometriosis/metabolism , Endometriosis/pathology , Estrogens/pharmacology , Estradiol/pharmacology , Estradiol/metabolism , Cell Movement , Endometrium/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology
2.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Article in English | MEDLINE | ID: mdl-33443222

ABSTRACT

Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7-/- mice to determine the role of TLR7 in ALD pathogenesis. In an alcoholic hepatitis (AH) mouse model, hepatic steatosis, injury, and inflammation were induced by chronic binge ethanol feeding in mice, and Tlr7 deficiency exacerbated these effects. Because these results demonstrated that endogenous TLR7 signaling activation is protective in the AH mouse model, we hypothesized that TLR7 activation may be an effective therapeutic strategy for ALD. Therefore, we investigated the therapeutic effect of TLR7 agonistic agent, 1Z1, in the AH mouse model. Oral administration of 1Z1 was well tolerated and prevented intestinal barrier disruption and bacterial translocation, which thus suppressed ethanol-induced hepatic injury, steatosis, and inflammation. Furthermore, 1Z1 treatment up-regulated the expression of antimicrobial peptides, Reg3b and Reg3g, in the intestinal epithelium, which modulated the microbiome by decreasing and increasing the amount of Bacteroides and Lactobacillus, respectively. Additionally, 1Z1 up-regulated intestinal interleukin (IL)-22 expression. IL-22 deficiency abolished the protective effects of 1Z1 in ethanol-induced liver and intestinal damage, suggesting intestinal IL-22 as a crucial mediator for 1Z1-mediated protection in the AH mouse model. Collectively, our results indicate that TLR7 signaling exerts protective effects in the AH mouse model and that a TLR7 ligand, 1Z1, holds therapeutic potential for the treatment of AH.


Subject(s)
Ethanol/toxicity , Interleukins/metabolism , Intestinal Mucosa/metabolism , Liver Diseases, Alcoholic/drug therapy , Membrane Glycoproteins/metabolism , Signal Transduction/drug effects , Toll-Like Receptor 7/metabolism , Administration, Oral , Animals , Bacteroides/drug effects , Disease Models, Animal , Fatty Liver/complications , Fatty Liver/genetics , Fatty Liver/metabolism , Female , Gastrointestinal Microbiome/drug effects , Inflammation/complications , Inflammation/genetics , Inflammation/metabolism , Intestinal Mucosa/drug effects , Lactobacillus/drug effects , Ligands , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/physiopathology , Membrane Glycoproteins/agonists , Membrane Glycoproteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs , Pancreatitis-Associated Proteins/genetics , Pancreatitis-Associated Proteins/metabolism , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Pore Forming Cytotoxic Proteins/genetics , Pore Forming Cytotoxic Proteins/metabolism , Signal Transduction/genetics , Tight Junctions/drug effects , Tight Junctions/pathology , Toll-Like Receptor 7/agonists , Toll-Like Receptor 7/genetics , Interleukin-22
3.
J Gastroenterol Hepatol ; 37(4): 727-733, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35064597

ABSTRACT

BACKGROUND AND AIM: Serum glycans are known to be good markers for the early diagnosis and prognostic prediction in many cancers. The aims of this study were to reveal the serum glycan changes comprehensively during the process of carcinogenesis from colorectal adenoma (CRA) to colorectal cancer (CRC) and to evaluate the usefulness of the glycan profiles as clinical markers for CRC. METHODS: Serum samples were obtained from 80 histologically proven CRC and 36 CRA cases. The levels of glycans in the serum were examined with a comprehensive, quantitative, high-throughput unique glycome analysis, and their diagnostic and prognostic abilities were evaluated. RESULTS: Among 34 stably detected glycans, nine were differentially expressed between CRC and CRA. Serum levels of hybrid type glycans were increased in patients with CRC compared with those with CRA (P < 0.001), and both hybrid-type and multi-antennary glycans were significantly increased in advanced cancer cases. The glycan, m/z 1914, showed the highest diagnostic value among the decreased glycans, whereas m/z 1708 showed the highest among the increased glycans. The glycan ratio m/z 1708/1914 showed a higher area under the receiver operating characteristic curve (0.889) than any other single glycan or conventional tumor marker, such as carcinoembryonic antigen (0.766, P = 0.040) and carbohydrate antigen 19-9 (0.615, P < 0.001). High m/z 1708/1914 was also correlated with an advanced cancer stage and short overall survival. CONCLUSION: Serum glycans, especially the m/z 1708/1914 ratio, were useful for the diagnosis, staging, and prognosis prediction of CRC.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Colorectal Neoplasms/diagnosis , Humans , Polysaccharides , Prognosis , ROC Curve
4.
Biol Pharm Bull ; 45(10): 1438-1443, 2022.
Article in English | MEDLINE | ID: mdl-36184501

ABSTRACT

Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.


Subject(s)
Agaricales , Neuroprotective Agents , Animals , Estradiol/pharmacology , Estrogen Receptor alpha , Estrogen Receptor beta , Female , Genistein , Hericium , Humans , Methanol , Ovariectomy , Phytoestrogens , Rats , Weight Gain
5.
BMC Gastroenterol ; 21(1): 28, 2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33441096

ABSTRACT

BACKGROUND: Only a few reports have assessed the effectiveness of endoscopic biliary drainage (EBD) in hepatocellular carcinoma (HCC) patients with obstructive jaundice and liver dysfunction. METHODS: This was a retrospective study based on the clinical databases from the Okayama University Hospital and 10 affiliated hospitals. All patients received EBD for jaundice or liver dysfunction. The indication for EBD was aggravation of jaundice or liver dysfunction with intrahepatic bile duct (IHBD) dilation. The technical and clinical success rate, complications, factors associated with clinical failure, and survival duration were evaluated. RESULTS: A total of 107 patients were enrolled in this study. Technical success was achieved in 105 of 107 patients (98.1%). Clinical success was achieved in 85 of 105 patients (81%). Complications related to endoscopic retrograde cholangiography (ERC) occurred in 3 (2.8%) patients. Child-Pugh class C (odds ratio 3.90, 95% confidence interval [CI] 1.47-10.4, p = 0.0046) was the only factor associated with clinical failure, irrespective of successful drainage. The median survival duration was significantly longer in patients with clinical success than in those without clinical success (5.0 months vs. 0.93 months; hazard ratio [HR] 3.2, 95% CI 1.87-5.37). HCC Stage I/II/III (HR 0.57, CI 0.34-0.95, p = 0.032), absence of portal thrombosis (HR 0.52, CI 0.32-0.85, p = 0.0099), and clinical success (HR 0.39, CI 0.21-0.70, p = 0.0018) were significant factors associated with a long survival. CONCLUSIONS: EBD for obstructive jaundice and liver dysfunction in patients with HCC can be performed safely with a high technical success rate. Clinical success can improve the survival duration, even in patients expected to have a poor prognosis. TRIAL REGISTRATION: Retrospectively registered.


Subject(s)
Carcinoma, Hepatocellular , Cholestasis , Jaundice, Obstructive , Liver Neoplasms , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholestasis/etiology , Cholestasis/therapy , Drainage , Humans , Jaundice, Obstructive/etiology , Jaundice, Obstructive/therapy , Liver Neoplasms/complications , Liver Neoplasms/therapy , Retrospective Studies , Treatment Outcome
6.
J Obstet Gynaecol Res ; 47(3): 941-948, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33410266

ABSTRACT

AIM: Endothelial reactivity is inhibited and oxidative stress is enhanced in women with endometriosis. Testosterone may adversely affect lipids and endothelium. We investigated the effects of androgenic properties of progestins combined with ethinyl estradiol (EE) on endothelial function, lipids and free radical production in such women. METHODS: Women with endometriosis were treated with 20 µg EE + 3 mg drospirenone (DRSP) or 35 µg EE + 1 mg norethisterone (NET) for 3 months. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, copper (Cu), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitrite/nitrate, endothelin-1 and asymmetrical dimethylarginine (ADMA) were measured before and after treatment. Flow-mediated vasodilation (FMD) of the brachial artery was measured by ultrasonography. RESULTS: DRSP group, but not NET group, significantly increased FMD and concentrations of nitrite/nitrate and small dense LDL cholesterol, while decreased endothelin-1 concentrations. In both groups, ADMA and LDL cholesterol concentrations were significantly decreased, but triglyceride, SHBG, d-ROMs, Cu and ceruloplasmin concentrations increased, and BAP concentrations did not change. DRSP group significantly increased HDL cholesterol concentrations, whereas NET group decreased its concentrations. Changes in triglyceride correlated positively either with changes in SHBG (r = 0.57, P < 0.001) or with small dense LDL cholesterol (r = 0.45, P = 0.005). Changes in Cu correlated positively with changes in d-ROMs (r = 0.87, P < 0.001). CONCLUSION: Androgenic properties of progestin may counteract EE's favorable effects on endothelial function and HDL cholesterol, while eliminating its adverse effects on increased triglyceride-induced small dense LDL cholesterol in women with endometriosis.


Subject(s)
Endometriosis , Progestins , Androgens , Cholesterol , Contraceptives, Oral, Combined/adverse effects , Endometriosis/drug therapy , Endothelium , Ethinyl Estradiol , Female , Free Radicals , Humans , Lipids
7.
J Biol Chem ; 294(33): 12359-12369, 2019 08 16.
Article in English | MEDLINE | ID: mdl-31235522

ABSTRACT

Excessive alcohol consumption induces intestinal dysbiosis of the gut microbiome and reduces gut epithelial integrity. This often leads to portal circulation-mediated translocation of gut-derived microbial products, such as lipopolysaccharide (LPS), to the liver, where these products engage Toll-like receptor 4 (TLR4) and initiate hepatic inflammation, which promotes alcoholic liver disease (ALD). Although the key self-destructive process of autophagy has been well-studied in hepatocytes, its role in macrophages during ALD pathogenesis remains elusive. Using WT and myeloid cell-specific autophagy-related 7 (Atg7) knockout (Atg7ΔMye) mice, we found that chronic ethanol feeding for 6 weeks plus LPS injection enhances serum alanine aminotransferase and IL-1ß levels and augments hepatic C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) expression in WT mice, a phenotype that was further exacerbated in Atg7ΔMye mice. Atg7ΔMye macrophages exhibited defective mitochondrial respiration and displayed elevated mitochondrial reactive oxygen species production and inflammasome activation relative to WT cells. Interestingly, compared with WT cells, Atg7ΔMye macrophages also had a drastically increased abundance and nuclear translocation of interferon regulatory factor 1 (IRF1) after LPS stimulation. Mechanistically, LPS induced co-localization of IRF1 with the autophagy adaptor p62 and the autophagosome, resulting in subsequent IRF1 degradation. However, upon p62 silencing or Atg7 deletion, IRF1 started to accumulate in autophagy-deficient macrophages and translocated into the nucleus, where it induced CCL5 and CXCL10 expression. In conclusion, macrophage autophagy protects against ALD by promoting IRF1 degradation and removal of damaged mitochondria, limiting macrophage activation and inflammation.


Subject(s)
Autophagic Cell Death , Chemical and Drug Induced Liver Injury/metabolism , Ethanol/adverse effects , Interferon Regulatory Factor-1/metabolism , Macrophages/metabolism , Mitochondria, Liver/metabolism , Proteolysis , Animals , Autophagy-Related Protein 7/genetics , Autophagy-Related Protein 7/metabolism , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/pathology , Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Chemokine CXCL10/genetics , Chemokine CXCL10/metabolism , Ethanol/pharmacology , Interferon Regulatory Factor-1/genetics , Lipopolysaccharides/toxicity , Liver/metabolism , Liver/pathology , Macrophages/pathology , Mice , Mice, Knockout , Mitochondria, Liver/genetics , Mitochondria, Liver/pathology
8.
Oncology ; 98(5): 311-317, 2020.
Article in English | MEDLINE | ID: mdl-32135540

ABSTRACT

BACKGROUND: Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC. OBJECTIVE: A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study. METHODS: The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS). RESULTS: The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses. CONCLUSIONS: The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.


Subject(s)
Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/blood , Liver Neoplasms/genetics , Mutation/genetics , Promoter Regions, Genetic/genetics , Telomerase/genetics , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Cohort Studies , Female , Humans , Liver/pathology , Male , Middle Aged , Prognosis , Telomerase/blood
9.
Biol Pharm Bull ; 43(3): 546-549, 2020.
Article in English | MEDLINE | ID: mdl-32115513

ABSTRACT

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.


Subject(s)
Estrogens/deficiency , Garlic , Maze Learning/drug effects , Memory Disorders/drug therapy , Ovariectomy/adverse effects , Plant Extracts/pharmacology , Animals , Body Weight/drug effects , Female , Memory/drug effects , Rats
10.
J Obstet Gynaecol Res ; 43(12): 1880-1886, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28984058

ABSTRACT

AIM: Risk factors for cisplatin-induced nephrotoxicity (CIN) vary by population. This study aimed to assess risk factors for CIN in patients with gynecological cancer. METHODS: Patients who underwent cisplatin-based chemotherapy for gynecological cancer between January 2009 and December 2015 at Aichi Medical University School of Medicine were included in this study. CIN was defined according to the 'risk, injury, failure, loss, and end-stage kidney disease' (RIFLE) criteria and classified as either risk (Class R) or injury (Class I). Analyses were performed using univariate and multivariate logistic regression models. RESULTS: Among 112 patients enrolled, 30 had CIN. Multivariate analysis revealed that hydration with magnesium (odds ratio [OR], 0.223), history of cisplatin use (OR, 4.420), and hypoalbuminemia (OR, 4.170) were risk factors for Class R, and that frequency of cisplatin administration (OR, 5.620) and hydration with magnesium (OR, 0.216) were risk factors for Class I. CONCLUSION: This study confirmed that hydration without magnesium, history of cisplatin use, frequency of cisplatin administration, and hypoalbuminemia are significant risk factors for CIN.


Subject(s)
Cisplatin/adverse effects , Genital Neoplasms, Female/drug therapy , Kidney Diseases/chemically induced , Adult , Aged , Cisplatin/therapeutic use , Female , Humans , Hypoalbuminemia/complications , Magnesium/administration & dosage , Magnesium/adverse effects , Middle Aged , Multivariate Analysis , Risk Factors
12.
J Gastroenterol Hepatol ; 30(3): 600-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25160604

ABSTRACT

BACKGROUND AND AIM: Inappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis (PSC). We evaluated the associations of expressions of toll-like receptor (TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in the biliary epithelial cells (BECs) with clinical features of PSC patients. METHODS: We retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation. RESULTS: TLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores. CONCLUSIONS: In PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker.


Subject(s)
Carrier Proteins/analysis , Carrier Proteins/genetics , Cholangitis, Sclerosing/immunology , Epithelial Cells/immunology , Gene Expression , Immunity, Innate/immunology , Toll-Like Receptor 4/analysis , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/analysis , Toll-Like Receptor 9/genetics , Adolescent , Adult , Aged , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/immunology , Bile Ducts, Intrahepatic , Biliary Tract/cytology , Biliary Tract/immunology , Child , Cholangiocarcinoma/genetics , Cholangiocarcinoma/immunology , Cholangitis, Sclerosing/genetics , Disease Progression , Female , Humans , Immunity, Innate/genetics , Immunohistochemistry , Liver Transplantation , Male , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein , Predictive Value of Tests , Prognosis , Retrospective Studies , Young Adult
13.
Phytother Res ; 29(12): 1950-5, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26443289

ABSTRACT

Young coconut juice (Cocos nucifera Linn.) (YCJ) has traditionally been consumed to alleviate symptoms associated with menopause by women in Southeast Asia. The aim of the present study was to determine the effects of YCJ on bone metabolism in ovariectomized rats. Female 10-week-old Wistar rats were randomly assigned to the following 4 groups: Baseline, Sham, Ovx, and Ovx + YCJ (n = 10 rats per group). Rats in the Baseline group were sacrificed immediately, and those in the other groups were subjected to either sham operation (Sham) or bilateral ovariectomy (Ovx and Ovx + YCJ). The Ovx + YCJ rats were administered 5×-concentrated YCJ at a dose of 10 mL/kg body weight per day. Six weeks after surgery, the rats were sacrificed, and indices of bone mass and bone histomorphometry were measured. The bone mineral density of the left femur was significantly higher in the Ovx + YCJ group compared with the Ovx group. In addition, the Ovx + YCJ group showed significantly higher measurements for bone formation rate compared with the Ovx group. These findings suggest that YCJ supplementation has a positive effect on bone metabolism and thus represents a possible intervention to slow the bone loss observed following menopause.


Subject(s)
Bone Density/drug effects , Bone Diseases, Metabolic/drug therapy , Cocos/chemistry , Dietary Supplements , Osteogenesis/drug effects , Animals , Disease Models, Animal , Female , Femur/drug effects , Ovariectomy , Rats , Rats, Wistar
14.
Nihon Rinsho ; 73(4): 639-43, 2015 Apr.
Article in Japanese | MEDLINE | ID: mdl-25936154

ABSTRACT

Osteoporosis is more commonly found in women, thus making women more susceptible to fracture than men. The growth period is crucial to skeletal development, resulting in larger and stronger bones in males than in females. Estrogen deficiency after menopause is strongly associated with rapid resorption and loss of bone density, which contrasts with the gradual decline in sex steroids and bone mineral density seen in aging men. Although estrogen deficiency is more pronounced in women, it also plays a major role in the pathogenesis of osteoporosis in men.


Subject(s)
Osteoporosis , Sex Characteristics , Bone Density , Estrogens/metabolism , Female , Gonadal Steroid Hormones/metabolism , Humans , Male , Osteoporosis/epidemiology , Osteoporosis/etiology , Osteoporosis/physiopathology , Osteoporotic Fractures
15.
Hepatol Res ; 44(13): 1299-307, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24506172

ABSTRACT

AIM: Recently, serum levels of anti-programmed cell death-1 (anti-PD-1) antibodies have been reported to be useful for the discrimination of type 1 autoimmune hepatitis (AIH) from drug-induced liver injury (DILI) and to be associated with clinical features of type 1 AIH. This multicenter study aimed to validate the usefulness of serum anti-PD-1 antibody as a serological marker for type 1 AIH. METHODS: Serum samples before the initiation of corticosteroid treatment were obtained from 71 type 1 AIH patients and 37 DILI patients. Serum levels of anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. RESULTS: Serum levels of anti-PD-1 antibodies were higher in type 1 AIH patients than in DILI patients (P < 0.001). The receiver-operator curve analysis showed that serum levels of anti-PD-1 antibodies were useful for the discrimination of type 1 AIH from DILI (area under the curve, 0.80). On the other hand, the multivariate Cox proportional hazard model showed that positivity for serum anti-PD-1 antibody, probable diagnosis based on the revised scoring system proposed by the International Autoimmune Hepatitis Group, and prothrombin activity of less than 60% were associated with the later normalization of serum transaminase levels. During the clinical course, the disease relapsed more frequently in patients positive for serum anti-PD-1 antibody (36% vs 11%). CONCLUSION: This study suggests that serum anti-PD-1 antibody is useful for the diagnosis of type 1 AIH as an auxiliary diagnostic marker, and that serum levels of anti-PD-1 antibodies reflect clinical features of type 1 AIH.

16.
J Gastroenterol Hepatol ; 29(1): 110-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23869988

ABSTRACT

BACKGROUND AND AIM: Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. METHODS: Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance + 2 standard deviations in healthy volunteers. RESULTS: Prevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r = 0.31, P = 0.030) and alanine aminotransferase (r = 0.31, P = 0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. CONCLUSIONS: Serum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.


Subject(s)
Autoantibodies/blood , Hepatitis, Autoimmune/diagnosis , Programmed Cell Death 1 Receptor/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Hepatitis, Autoimmune/classification , Humans , Lymphocytes/immunology , Male , Middle Aged , Programmed Cell Death 1 Receptor/physiology , Young Adult
17.
J Gastroenterol Hepatol ; 29(2): 337-43, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23869873

ABSTRACT

BACKGROUND AND AIM: Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. METHODS: The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. RESULTS: The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045). CONCLUSION: HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.


Subject(s)
Antiviral Agents/administration & dosage , Health Surveys/methods , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Quality of Life , Ribavirin/administration & dosage , Aged , Drug Therapy, Combination , Female , Forecasting , Hepacivirus/classification , Hepatitis C, Chronic/psychology , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferons , Interleukins/genetics , Logistic Models , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Recombinant Proteins/administration & dosage , Serotyping , Treatment Outcome
18.
J Obstet Gynaecol Res ; 40(2): 599-602, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24118367

ABSTRACT

The effects of airbag deployment in motor vehicle accidents (MVA) on the fetus are poorly understood. A 22-year-old woman at 24 weeks of gestation collided with a telephone pole while driving. She was restrained and an airbag deployed. Although she had no major injuries, she experienced decreased fetal movements. Fetal heart rate (FHR) monitoring revealed loss of variability without any evidence of abruptio placentae, and 4 days later, the variability spontaneously recovered. Two weeks after the MVA, ultrasonography showed unilateral ventricular dilatation suggestive of fetal brain injury. Magnetic resonance imaging revealed subdural hematoma, intraventricular hemorrhage and cystic lesions, interpreted as indirect (hypoxic-ischemic) and direct (hemorrhagic) intracranial injuries. After MVA with airbag deployment, FHR monitoring can show a transient loss of variability, which may precede the appearance of fetal brain injury.


Subject(s)
Air Bags/adverse effects , Brain Injuries/diagnosis , Nervous System Diseases/etiology , Prenatal Exposure Delayed Effects/etiology , Prenatal Injuries/diagnosis , Accidents, Traffic , Brain Injuries/etiology , Brain Injuries/physiopathology , Child, Preschool , Female , Fetus , Heart Rate, Fetal , Humans , Pregnancy , Prenatal Injuries/etiology , Prenatal Injuries/physiopathology , Young Adult
19.
Kyobu Geka ; 67(2): 149-52, 2014 Feb.
Article in Japanese | MEDLINE | ID: mdl-24743487

ABSTRACT

Chylothorax - a serious postoperative complication of thoracic surgery - is associated with high morbidity and mortality, and re-exploration is required in many such cases. A 33-year-old male patient had undergone an extra-anatomic bypass for the treatment of coarctation of the aorta. Persistent chylothorax developed as a complication postoperatively. Octreotide acetate was administered 11 days postoperatively, which resolved the chylothorax without the need for surgical intervention. The patient was discharged from our hospital without any complications at 40 days postoperatively. In the present report, we describe this case and a provide a review of the literature.


Subject(s)
Aortic Coarctation/surgery , Chylothorax/drug therapy , Gastrointestinal Agents/therapeutic use , Octreotide/therapeutic use , Adult , Chylothorax/etiology , Humans , Male , Postoperative Complications
20.
Cureus ; 16(1): e52296, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38357044

ABSTRACT

Gynecologic malignancies sometimes affect women before menopause. Aggressive treatments, such as surgery, chemotherapy, and/or radiotherapy, often lead to premature menopause. Hormone replacement therapy (HRT), typically used for managing menopause-associated health issues, may be limited by tumor sensitivity to estrogen. Here, we present a case of a 37-year-old woman seeking fertility, who was diagnosed with a serous borderline ovarian tumor (BOT). Fertility-preserving surgery and in-vitro fertilization resulted in a twin pregnancy. During a postpartum amenorrheic period, there was no recurrence. However, she experienced a rapid recurrence of the disease following the resumption of menstruation and underwent radical surgery. This rapid recurrence after menstruation resumed suggests potential estrogen sensitivity. Close postoperative monitoring has been ongoing without HRT.

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