Cerebral oxygenation and body mass index association with cognitive function in chronic kidney disease patients without dialysis: a longitudinal study.

In chronic kidney disease (CKD) patients, the prevalence of cognitive impairment increases with CKD progression; however, longitudinal changes in cognitive performance remain controversial. Few reports have examined the association of cerebral oxygenation with cognitive function in longitudinal studies. In this study, 68 CKD patients were included. Cerebral regional oxygen saturation (rSO2) was monitored. Cognitive function was evaluated using mini-mental state examination (MMSE) score. Clinical assessments were performed at study initiation and 1 year later. MMSE score was higher at second measurement than at study initiation (p = 0.022). Multivariable linear regression analysis showed that changes in MMSE were independently associated with changes in body mass index (BMI, standardized coefficient: 0.260) and cerebral rSO2 (standardized coefficient: 0.345). This was based on clinical factors with p < 0.05 (changes in BMI, cerebral rSO2, and serum albumin level) and the following confounding factors: changes in estimated glomerular filtration rate, hemoglobin level, proteinuria, salt and energy intake, age, presence of diabetes mellitus, history of comorbid cerebrovascular disease, and use of renin-angiotensin system blocker. Further studies with a larger sample size and longer observational period are needed to clarify whether maintaining BMI and cerebral oxygenation improve or prevent the deterioration of cognitive function.

Prevention effect of quercetin and its glycosides on obesity and hyperglycemia through activating AMPKα in high-fat diet-fed ICR mice.

Quercetin and its glycosides possess various health beneficial functions, but comparative study of them on energy metabolism in different tissues are not well studied. In this study, we investigated AMP-activated protein kinase regulated glucose metabolism in the skeletal muscle and lipid metabolism in the white adipose tissue and liver to compare the effectiveness of quercetin and its glycosides, namely isoquercitrin, rutin, and enzymatically modified isoquercitrin, in male ICR mice. The mice were fed a standard or high-fat diet supplemented with 0.1% quercetin and its glycosides for 13 weeks. Quercetin glycosides, but not quercetin, decreased body weight gain and fat accumulation in the mesenteric adipose tissue in high-fat groups. All compounds decreased high-fat diet-increased plasma glucose and insulin levels. Moreover, all compounds significantly increased AMP-activated protein kinase phosphorylation in either standard or high-fat diet-fed mice in all tissues tested. As its downstream events, all compounds induced glucose transporter 4 translocation in the muscle. In the white adipose tissue and liver, all compounds increased lipogenesis while decreased lipolysis. Moreover, all compounds increased browning markers and decreased differentiation markers in adipose tissue. Therefore, quercetin and its glycosides are promising food components for prevention of adiposity and hyperglycemia through modulating AMP-activated protein kinase-driven pathways.

Effects of dietary intake and nutritional status on cerebral oxygenation in patients with chronic kidney disease not undergoing dialysis: A cross-sectional study.

BACKGROUND: Dietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited. METHODS: This was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection. RESULTS: Multivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p < 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake. CONCLUSIONS: Cerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients.

Enzymatically modified isoquercitrin promotes energy metabolism through activating AMPKα in male C57BL/6 mice.

Quercetin possesses various health beneficial functions, but its poor bioavailability limits these functions. Enzymatically modified isoquercitrin (EMIQ) is a quercetin glycoside with a greater bioavailability than quercetin. In this study, we investigated whether EMIQ regulates energy metabolism in mice and its underlying molecular mechanism. Male C57BL/6 mice were fed a normal diet with different doses of EMIQ or quercetin (0.02%, 0.1% and 0.5%) for two weeks. Supplementation with 0.1% EMIQ significantly decreased white adipose tissue (WAT) weight. Supplementation with 0.02% and 0.1% EMIQ promoted phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in the WAT, liver, and muscle. In the WAT, 0.1% EMIQ downregulated peroxisome proliferator-activated receptor (PPAR)γ, CCAAT-enhancer-binding protein (C/EBP)α, C/EBPß, and sterol regulatory element-binding protein 1 expression, as well as upregulated mitochondrial uncoupling protein (UCP) 2 and carnitine palmitoyltransferase-1 expression. Supplementation with 0.1% EMIQ also promoted the expression of thermogenesis-associated factors including PPARγ coactivator α (PGC-1α), UCP1, PR-domain containing protein 16, and sirtuin 1 in the WAT. In the liver, EMIQ promoted the phosphorylation of acetyl-CoA carboxylase, and increased the expression of PPARα, constitutive androstane-receptor, and farnesoid X receptor. Furthermore, supplementation with 0.02% or 0.1% EMIQ suppressed the plasma glucose level accompanied by the translocation of glucose transporter 4 to the plasma membrane of the muscle. Our results suggest that EMIQ is a potential food additive for the regulation of energy metabolism through AMPK phosphorylation.

Live birth following laparoscopic fertility-sparing surgery for papillary thyroid carcinoma arising from mature ovarian cystic teratoma: A case report.

Papillary thyroid carcinoma arising from ovarian mature cystic teratoma is clinically rare. We herein present a case of live birth following two laparoscopic surgeries for papillary thyroid carcinoma arising in a mature ovarian cystic teratoma. A 30-year-old female patient, gravida 1 para 1, was treated by laparoscopic bilateral ovarian cystectomy for suspicion of bilateral mature cystic teratoma. The diagnosis of papillary thyroid carcinoma arising from right ovarian mature cystic teratoma was established based on postoperative pathological examination of the tumor. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. The patient underwent laparoscopic fertility-preserving unilateral (right) salpingo-oophorectomy. Following an extensive discussion with the patient and her family, appropriate informed consent was obtained for the treatment option and the patient and her family chose to preserve her fertility. She could have a baby following the treatment and no evidence of disease for 6 years. Gynecologists should be aware of the possibility of such rare cases, and the available surgical interventions should be fully discussed with patients who wish to preserve their fertility. Laparoscopic fertility-sparing surgery may be a feasible option when encountering such a rare condition.

Postpartum Methicillin-Resistant Staphylococcus aureus Toxic Shock Syndrome Caused by a Perineal Infection.

Although toxic shock syndrome (TSS) is rare, multiorgan failure can occur without early identification and appropriate therapy. In particular, a few cases of postpartum TSS due to methicillin-resistant Staphylococcus aureus (MRSA) have been reported. Here, we describe a rare case in which a 32-year-old Japanese woman had TSS due to MRSA that was caused by a perineal infection after a normal vaginal delivery. Twelve days after giving birth to a healthy child, she was readmitted to our hospital due to a 2-day fever and perineal pain without uterine tenderness. She developed emesis and watery diarrhea on the night of admission. On the second day, a diffuse cutaneous macular rash appeared over her trunk. Laboratory data revealed deteriorated renal function and thrombocytopenia. Her history and clinical results were compatible with a typical course of TSS. Administration of ceftriaxone and clindamycin was started immediately after admission and was effective. The patient recuperated steadily over the next week with desquamation of the skin. MRSA was isolated from her vaginal discharge and was found to produce TSS toxin 1 (TSST-1). Furthermore, since MRSA was not detected in the nasal and vaginal cavity during pregnancy, it suggests that vaginal colonization can also occur postpartum and be the disease source in mothers. Therefore, MRSA infections should be considered when treating for postpartum TSS.

Non-neural granular cell tumor of the uterine corpus mimicking uterine leiomyoma: A case report.

Non-neural granular cell tumors (GCTs) are clinically rare, whereas cases arising in the uterine corpus are exceedingly rare. Only three uterine cervical cases of GCTs have been reported to date and, to the best of our knowledge, there are no reports of GCT of the uterine corpus in the literature. We herein describe the first case of non-neural GCT arising from the uterine corpus reported to date. A 55-year-old premenopausal woman was referred to the Department of Obstetrics and Gynecology of Hashimoto Municipal Hospital (Wakayama, Japan) with a suspected uterine tumor. The tumor presented as a uterine leiomyoma-like mass on radiological examinations, but the diagnosis of non-neural GCT was established based on pathological and immunohistochemical examinations. Microscopically, histological examination of the entire surgical specimen revealed large polygonal cells with abundant eosinophilic granular cytoplasm and round to oval nuclei. Immunohistochemistry revealed positive periodic acid-Schiff staining of the cytoplasmic granules, which was resistant to diastase. In addition, the tumor cells stained positive for CD68, but negative for S-100, neuron-specific enolase, cytokeratin, CD34, α-smooth muscle actin, desmin, estrogen receptor and progesterone receptor. It is important for gynecologists to be aware of the possibility of non-neural GCT of the uterine corpus, for which accurate diagnosis, complete resection and long-term follow-up are crucial, as it may be easily misdiagnosed as uterine leiomyoma.

Omental synovial sarcoma mimicking an ovarian malignancy: A case report.

Synovial sarcoma is clinically rare, and cases of synovial sarcoma arising in the omentum are particularly rare. Only 3 cases have been reported in the literature to dtae, and they were associated with a poor prognosis. We herein report a rare case of aggressive primary omental synovial sarcoma presenting as an ovarian malignancy. A 53-year-old multigravida woman was referred to our hospital due to progressive abdominal distension. Magnetic resonance imaging revealed a large heterogeneous mass with an irregular component occupying the lower abdominal cavity, with an intact uterus. Intraoperative examination revealed a solid mass arising from the lower omentum. The diagnosis of omental synovial sarcoma was established based on postoperative pathological and immunohistochemical examination of the tumor. The patient underwent multiple surgical resection procedures due to the development of metastases in the liver, lungs and abdominal cavity and received adjuvant chemotherapy including doxorubicin-ifosfamide, pazopanib and trabectedin. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. Thus, gynecologists should be aware of the possibility of omental synovial sarcoma, and combined surgical and chemotherapeutic interventions are required to control such aggressive tumors.

A Third Surgically Managed Ectopic Pregnancy after Two Salpingectomies Involving the Opposite Tube.

Recurrent ectopic pregnancy in a remnant fallopian tube after ipsilateral salpingectomy is clinically rare. We report the extremely rare case of a third recurrent ectopic pregnancy after two previous salpingectomy procedures involving the opposite tube. A 26-year-old woman, gravida 3 para 0, experienced three ectopic pregnancies brought about by natural conception, all of which were treated surgically (right partial salpingectomy, right remnant tube resection, and left total salpingectomy). During the two salpingectomy procedures involving the right tube, the patency of the intact left tube was intraoperatively confirmed with indigo carmine. The most appropriate surgical intervention should be discussed when managing recurrent ectopic pregnancies. It might be necessary to perform total salpingectomy to reduce the risk of future recurrence on the remaining tube.

The potent peptide antagonist to angiogenesis, C16Y, and cisplatin act synergistically in the down-regulation of the Bcl-2/Bax ratio and the induction of apoptosis in human ovarian cancer cells.

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.

Localisation of phosphorylated mTOR expression is critical to tumour progression and outcomes in patients with endometrial cancer.

Correlations between mammalian target of rapamycin (mTOR) expression, and clinicopathological features, outcome and Akt expression in endometrial endometrioid adenocarcinoma (EEC) were investigated. Tumour samples were obtained from 82 patients with EEC who had undergone hysterectomy, and phosphorylated mTOR (p-mTOR) and Akt (p-Akt) expression in the cytoplasm and nucleus was analysed by immunohistochemical staining. Nuclear p-mTOR was significantly elevated in poorly differentiated tumours and positively correlated with lymph node involvement (P = 0.05). Nuclear p-mTOR expression was associated with significantly shorter relapse-free survival (RFS) (P<0.01) and slightly shorter overall survival (OS) (P = 0.08). Cytoplasmic expression of p-mTOR was not correlated with any clinicopathological factors. Although not significant, cytoplasmic p-mTOR expression was associated with shorter PFS and OS (P = 0.09, P = 0.283, respectively). Neither cytoplasmic nor nuclear p-Akt expression was associated with clinicopathological factors or with survival. Localisation of p-mTOR may be critical for tumour progression and outcomes in patients with EEC.

Expression of heat shock protein 27 with the transition from proliferation to differentiation of acinar precursor cell in regenerating submandibular gland of rats.

Heat shock protein 27 (Hsp27) has been suggested to participate in the cell proliferation and differentiation during tissue development. In fact, we have demonstrated the transient occurrence of Hsp27 during the differentiation of salivary gland acinar cells in postnatal rats. The purpose of the present study is to explore the potential role of Hsp27 in the proliferation and differentiation of the acinar cells during regeneration of the salivary gland. Using the experimental regeneration model of the rat submandibular gland after the release of duct ligation, the spatio-temporal localization of Hsp27 was investigated in immunohistochemistry in regenerating acini. No epithelial cells were immunoreactive for Hsp27 immediately after unligation, but Hsp27-immunoreactive cells were observed in regenerating acini located at the end portion of survived ductal tissues on the third day after unligation. The number of Hsp27-immunoreactive cells in regenerating acini reached its peak on the 5th day after unligation, and started to decline on the 7th day. They were undetectable on the 14th day. Importantly, the increase in the number of Hsp27-immunoreactive cells was preceded by the decline in the cell proliferative activity, and Hsp27-immunoreactivity declined and disappeared in conjunction with the progression of acinar cell differentiation, as judged by the double-immunostaining for Hsp27 and proliferating cell nuclear antigen, a cell proliferation marker, or glycine-rich protein-alpha, a specific marker of differentiated acinar cells. All the findings suggest that Hsp27 is expressed with the transition from the cell proliferation to differentiation of the acinar precursor cells during the regenerating process.

Expression of CYLD, NF-kappaB and NF-kappaB-related factors in salivary gland tumors.

The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant condition that confers a predisposition to multiple tumors of the skin appendages. CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis. Expression of CYLD has been detected in various organs, but its expression in salivary gland tumor (SGT) is still unknown. Adenoid cystic carcinoma (ACC) is a well known and typical malignant SGT ACC was previously known as cylindroma in view of its marked histological resemblance to dermal cylindroma. In this study, the expressions of CYLD and NF-kappaB mRNA in HSG, a human SGT cell line, were found to be increased by TNF-alpha stimulation. Immunohistochemistry clearly demonstrated the expression of CYLD and NF-kappaB-related factors in ACC tissue.

Induction of apoptosis in human salivary gland tumor cells by anti-NCAM antibody.

Neural cell adhesion molecule (NCAM) is a type of cell surface glycoprotein and a member of the immunoglobulin superfamily. It has been reported that NCAM may be associated with perineural invasion by malignant salivary gland tumors such as adenoid cystic carcinoma. We have previously demonstrated that NCAM is constitutively expressed in the human salivary gland tumor cell line HSG, in vitro. In the present study, we have aimed to clarify the hypothesis that NCAM-mediated inhibition of salivary gland tumor proliferation is caused by homophilic binding and involves the prevention of signal transduction for perineural invasion using HSG cells. NCAM mRNA and protein expression was found to decrease in a dose-dependent manner upon treatment with the anti-NCAM antibody (MAb NCAM) for 24 h. The MTT assay showed a significant reduction in the number of viable HSG cells. Confocal laser microscopy showed that HSG cells underwent apoptosis after treatment with MAb NCAM. The activation of caspases 3, 7 and 9 was observed in HSG cells after treatment with MAb NCAM, thus confirming that apoptosis was induced by the activated caspases. Apaf-1 activity was also detected in HSG cells in a dose-dependent manner after treatment with MAb NCAM. The up-regulation of TGF-beta1-mediated NCAM expression appeared to lead to the activation of homophilic NCAM binding, further accelerating HSG cell proliferation. In addition, the localization of NCAM in adenoid cystic carcinomas (ACCs) was examined using an immunohistochemical method. NCAM was slightly to moderately positive in 9 of 13 cases (69.2%) of ACC. These findings suggest that NCAM is associated not only with a cell-to-cell adhesion mechanism, but also with tumorigenesis, including growth, development and perineural invasion in human salivary gland tumors.