bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-BPR01-9: A CASE OF CYCLIC CUSHING'S SYNDROME DIAGNOSED WITH HYPERTENSION AND LEG EDEMA
Authors: Hayakawa Eri , Tomino Yuki , Chonabayashi Minami , Sugiyama Toru 
Published: January 2023

Background:
Cushing's syndrome (CS) is associated with hypertension in approximately 80% of cases, which contributes to the increased mortality risk. Few cases of intermittent hypertension due to cyclic CS(CCS) have been reported. Case presentation: A 66-year-old woman with no specific medical history was referred to our hospital for evaluation of hypertension and leg edema. The Cardiovascular examination showed no abnormality in her cardiac function. Laboratory findings revealed hypokalemia, hyperglycemia, and metabolic alkalosis. She was tentatively initiated on calcium channel blocker (CCB) and insulin therapy. The endocrine examination revealed elevated ACTH and cortisol without circadian variation, which responded to neither the 8 mg dexamethasone suppression test nor CRH stimulation, leading to the diagnosis of ACTH-dependent CS. CT, FDG/PET CT, and Octreotide scan showed no obvious lesion other than bilateral adrenal enlargement. Enhanced MRI showed a normal pituitary gland with neither adenoma nor pituitary stalk deviation/tilt. Since the etiology of CS was not confirmed, metyrapone administration was initiated as symptomatic treatment. Her serum ACTH and cortisol fell rapidly after the initiation of metyrapone, and her blood pressure (BP) and blood glucose levels improved accordingly, even without the use of CCB and insulin. Since both ACTH and cortisol became normalized after discharge, metyrapone was tapered off after 4 months. Furthermore, CT showed normalization of the adrenal enlargement. For the next two months, her ACTH and cortisol remained within the normal limits, and her BP, serum potassium and blood glucose were well controlled. However, she visited our hospital because of re-elevated BP thereafter and was found to have re-elevated ACTH and cortisol with bilateral adrenal enlargement as well as re-decreased serum potassium. Since her BP and serum potassium levels were not controlled well even after she resumed taking metyrapone, the dose of metyrapone was increased, spironolactone was added, and CCB was resumed. Another two months later, her ACTH and cortisol normalized without metyrapone again, and her BP was well-controlled accordingly. This cyclical course of ACTH/cortisol elevation strongly suggested CCS. Conclusion: CCS is a clinical syndrome that exhibits a periodic or irregular increasing pattern in cortisol, which is a rare type of CS. Confirmation of CCS diagnosis is only possible during periods of relapse. In the present case, elevated BP was an indicator of hormonal fluctuations that could be appropriately treated. We report here a case of CCS that was diagnosed because of a good correlation between BP and hormone levels.
PS-BPR02-7: SACUBITRIL VALSARTAN FOR REFRACTORY HYPERTENSION CAUSED BY PRIMARY ALDOSTERONISM: A CASE SERIES
Authors: Yamashita Tomohisa , Akazawa Chikako , Osanami Arata , Yano Toshiyuki , Saito Shigeyuki 
Published: January 2023

Introduction:
Primary aldosteronism (PA) is the disease characterized by inappropriately elevated autonomous adrenal aldosterone secretion, leading to the development of refractory hypertension. Patients with PA show higher nighttime blood pressure (BP) and lower nocturnal BP decline than those with essential hypertension. Angiotensin receptor neprilysin inhibitors (ARNIs) are a new class of cardiovascular agents characterized by their dual action on the renin angiotensin system and the natriuretic peptide system. Atrial natriuretic peptide has been shown to inhibit basal aldosterone secretion from adrenal cells in vitro.

Case Presentation:
A man in his 50 s was referred to our hospital due to vision loss and diagnosed with hypertensive retinopathy. His serum potassium level was below 3.5 mEq/L. A captopril test confirmed the diagnosis of PA, though a CT image revealed no adrenal adenoma. According to his discretion, medical treatment including a mineralocorticoid receptor antagonist, a calcium channel blocker, an angiotensin receptor blocker (ARB), an angiotensin converting enzyme inhibitor (ACEI), an alpha blocker and a beta blocker, were commenced. However, the result of ambulatory bloop pressure monitoring (ABPM) revealed his mean BP of 143/91 mmHg and his mean nighttime BP of 148/89 mmHg, indicating riser pattern. Switching from an ACEI, imidapril (10 mg per day), and an ARB, azilsartan (40 mg per day), to sacubitril/valsartan (200 mg per day) decreased his mean BP to 138/89 mmHg. Furthermore, his mean nighttime BP decreased to 122/79 mmHg, indicating that his nocturnal hypertension was improved by sacubitril/valsartan. Similar favorable effects of Sacubitril/valsartan on BP were found in three other patients with refractory hypertension caused by PA.

Discussion:
ARNIs are an appropriate treatment option for refractory hypertension caused by PA.
PS-B05-6: FABRY DISEASE MOUSE IS RESISTANT TO HIGH-SALT DIET-INDUCED HYPERTENSION PROBABLY VIA DYSFUNCTIONAL SODIUM TRANSPORTS AND AQUAPORIN 2
Authors: Chung Sungjin , Son Mina , Park Junkyu , Jo Wonji , Koh Eun Sil 
Published: January 2023

Background:
Fabry disease is a rare X-linked lysosomal storage disorder resulting from an error in glycosphingolipid metabolism caused by the GLA gene mutation. Patients with Fabry disease often have near normal or even low systemic blood pressure although the mechanism underlying such observed finding remains unexplained. This study examined whether a high salt intake could affect transport of sodium and water and induce hypertension in mice with Fabry disease.

Methods:
Fabry disease model mice (B6;129-Glatm1Kul/J) and wild-type (WT) mice received 8% or normal NaCl salt diet for 2 weeks.

Results:
A high-salt diet for 2 weeks generated higher blood pressure in WT mice but not in Fabry disease mice. Free water clearance (FWC) and electrolyte free water clearance (EFWC) in groups fed with a high salt diet were lower than those in groups fed with a normal salt diet. Both high salt-fed WT and Fabry disease mice had decreased gamma-subunit of epithelial Na channel (ENaC) compared with normal salt-fed groups. In Fabry disease mice fed a high-salt diet, there was an decrease in renal expressions of Na+/H+ exchanger isoform 3 (NHE3) and Na+-Cl- cotransporter (NCC) compared with WT mice fed a high-salt diet. Although renal expression of vasopressin V2 receptor (V2R) was upregulated in Fabry mice fed with a high salt diet, renal aquaporin 2 (AQP2) level failed to increase up to the level in WT mice fed with a high salt diet.

Conclusion:
These findings suggest that the decreased expression of NHE3 and NCC and impaired response of AQP2 in kidneys of Fabry disease to a salt load could be one of mechanisms by which Fabry disease could have resistance to the development of hypertension.
PS-B05-10: DIABETES MELLITUS AGGRAVATES BEHAVIORAL DEFICIT AND INCREASES SITE-SPECIFIC PHOSPHORYLATION OF TAU PROTEIN IN ALZHEIMER'S DISEASE MOUSE MODEL
Authors: Ito Yuki , Takeda Shuko , Nakajima Tsuneo , Oyama Akane , Takeshita Hikari , Miki Kunihiro , Takami Yoichi , Takeya Yasushi , Shimamura Munehisa , Rakugi Hiromi , Morishita Ryuichi 
Published: January 2023

Objective:
Numerous epidemiological studies have demonstrated that vascular risk factors including diabetes mellitus (DM) increase the risk of developing Alzheimer's disease (AD). However, the mechanisms underlying the pathological relationship between DM and AD remain largely unknown. Tau is a microtubule-associated protein that is predominantly expressed in the axons of neurons. More than 80 residues of tau can be potentially phosphorylated. Accumulation of hyperphosphorylated tau protein plays a role in neurodegeneration and cognitive impairment in patients with AD. Here, we developed a unique diabetic AD mouse model and analyzed behavioral phenotypes and biochemical changes occurring in the brain to investigate the impact of DM on tau pathology.

Design and method:
Tau-tg and WT mice were fed with either normal chow diet (NCD; 12% kcal fat, n = 9) or high-fat diet (HFD; 60% kcal fat, n = 10) from the age of one and a half to nine months. Metabolic parameters and behavioral phenotypes were assessed at eight months of age. Mice were then sacrificed at nine months of age and brains were analyzed histologically and biochemically. A quantitative proteomic analysis of protein phosphorylation was performed using brain extracts of tau-tg mice.

Results:
Tau-tg mice fed with HFD (HFD tau-tg) showed severe obesity and hyperinsulinemia compared with tau-tg mice fed with NCD (NCD tau-tg) (p < 0.01), with slight elevation of plasma glucose levels. HFD tau-tg showed exacerbation of motor impairments and decrement of habituation to novel environment. Histological analysis showed a significant decrease in the number of neurons in HFD tau-tg compared to NCD tau-tg. The amount of aggregated form of phospho-tau (Ser396) was increased in HFD tau-tg brain. Comprehensive phosphoproteomic analysis identified 11 phosphosites of tau significantly hyperphosphorylated in the brain of HFD tau-tg (p < 0.05).

Conclusions:
These results suggest that diabetic conditions such as obesity and hyperinsulinemia with minimal hyperglycemia exacerbate behavioral deficits in AD via hyperphosphorylation of tau protein. We identified specific phosphosites of tau involved in pathological relationship between DM and AD.
PS-B06-4: ADENINE NEPHROPATHY IS ALLEVIATED BY ANTI-INFLAMMATORY PROPERTY OF SODIUM BENZOATE
Authors: Oshima Yoichi , Wakino Shu , Kanda Takeshi , Tajima Takaya , Itoh Tomoaki , Uchiyama Kiyotaka , Yoshimoto Keiko , Sasabe Jumpei , Itoh Hiroshi 
Published: January 2023

Background:
D-amino acid oxidase (DAO), a molecule distributed in brain, liver, and kidney in human, oxidases d-amino acids to alpha-keto acids to produce hydrogen peroxides. Sodium benzoate (SB), a known DAO enzyme inhibitor, has anti-inflammatory property, although its effect has not been investigated in chronic kidney disease (CKD).

Methods:
Adenine induced CKD (AdCKD) or 2,8-dihydroxyadenine (2,8-DHA) nephropathy is applied for rodent CKD studies. AdCKD was induced by oral administration of adenine in C57BL/6JJcl mice with or without SB oral administration. AdCKD was also induced in DAO enzyme deficient mice (DAO-/-) and treated with or without SB. Human THP-1 cells and macrophages induced from THP-1 cells by phorbol 12-myristate 13-acetate were stimulated by LPS or TNF-alpha with or without SB to confirm the anti-inflammatory effect of SB.

Results:
AdCKD showed increased serum creatinine and urea nitrogen levels as well as kidney interstitial fibrosis and tubular atrophy score, which were significantly attenuated by the treatment of SB. Survival of AdCKD mice were significantly prolonged by 2.6-fold by SB administration. SB significantly decreased elevated kidney positive F4/80 immunohistochemistry area and renal mRNA level of macrophage markers and inflammatory markers of AdCKD. Human THP-1 cells and macrophages stimulated either by LPS or human TNF-alpha showed increased inflammatory gene mRNA expressions, which were significantly reduced by SB treatment.

Conclusions:
SB significantly ameliorated renal damage in AdCKD by suppressing inflammatory gene expressions and macrophage infiltration.
PS-B06-11: GLUCAGON-LIKE PEPTIDE-1 SUPPRESSES ACTIVATED EFFECTOR MEMORY T CELL SUBSETS IN THE FATTY LIVER INDUCED BY ANTI-CD3-ADNTIBODY ADMINISTRATION IN LEAN MICE
Authors: Itoh Arata , Yuki Kazunari , Irie Junichiro , Itoh Hiroshi 
Published: January 2023

Objective:
We previously invented a disease-model of hepatosteatosis, glucose tolerance and hyperlipidemia, typically observed in non-alcoholic fatty liver disease with metabolic syndrome, but without obesity, through activation of CD4-positive lymphocytes by anti-CD3 antibody administration in lean mice. We also showed that this model is CD4 T-cell dependent and glucagon-like-protein-1 receptor agonist reduces cytokine production in the liver with amelioration of fatty liver, hyperglycemia and hyperglycemia in this model. The precise mechanisms, however, remains unclear. We investigated how GLP-1RA targets and suppresses T cells.

Design and Method:
GLP-1R expression on activated T cell subsets in the liver and spleen was analyzed using flow-cytometry one day after administration of anti-CD3 antibody in the female lean Balb/c mice. Purified splenic CD4 T cells were differentiated into Th1, Th2, Th17 or regulatory T cells in-vitro and glp1r gene expression and GLP-1R protein expression were analyzed with real-time PCR and flow-cytometry, respectively.

Results:
anti-CD3 antibodies significantly increased GLP-1R+ CD62L- CD44+ effector-memory CD4 and CD8 T cells in the liver and GLP-1RA protected from increasing number of those CD4 and CD8 T cells in the liver in vivo. Activated and in-vitro induced Th1, Th2, Th17 and regulatory T cell subsets expresses express GLP-1R.

Conclusions:
GLP-1RA targets activated/effector-memory T cell subsets and reduces their proliferation and cytokine production.
PS-B07-5: EXERCISE TRAINING UPREGULATES FATTY ACID B;-OXIDATION WITH INCREASING PGC-1A AND PPARA IN THE KIDNEY OF DAHL SALT-SENSITIVE RATS
Authors: Takahashi Asako Namai , Takahashi Junta , Xu Lusi , Miura Takahiro , Kohzuki Masahiro , Ito Osamu 
Published: January 2023

Objective:
Exercise training (Ex) has anti-hypertensive and renal protective effects. Fatty acid metabolism in the kidney is involved in renal damage. In this study, we investigated the effects of the Ex on blood pressure, renal damages, and fatty acid metabolism in Dahl salt-sensitive rats.

Design and method:
Six-week-old male Dahl salt-sensitive rats were divided into three groups: 1) normal salt diet (NS); 2) high salt diet (HS); 3) HS+Ex. NS or HS groups were fed diet containing 0.6% or 8% NaCl. Treadmill running was performed in HS+Ex group for 8 weeks (5 days/week; 60 min/day at 16–20 m/min, 0% grade). Systolic blood pressure (SBP) was monitored by tail-cuff method. Renal function, histology and the expression of enzymes and regulators for fatty acid metabolism were then assessed.

Results:
HS significantly elevated SBP, and Ex did not change SBP. HS significantly decreased creatinine clearance, and Ex significantly ameliorated creatinine clearance. HS significantly increased urinary protein excretion, and Ex significantly suppressed urinary protein excretion. HS induced glomerular sclerosis, and Ex suppressed them. HS decreased the renal expression of enzymes for fatty acid β;-oxidation including carnitine palmitoyltransferase type I (CPTI) and very long, medium and short-chain acyl-CoA dehydrogenases (CADs) and their transcription factors; peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α). Ex increased the renal expression of CPTI, CADs, PPARα and PGC-1α.

Conclusions:
Ex improves HS-induced renal damage with fatty acid β;-oxidation with increasing PPARα and PGC-1α in Dahl salt-sensitive rats in a systolic blood pressure-independent manner. These results suggest that Ex may have beneficial effects in HS-induced renal damage.
PS-B07-10: SUPEROXIDE DISMUTASE PROFILE OF LIVER TISSUE IN HYPERURICEMIA RATS AFTER DAILY CONSUMPTION OF COFFEE
Authors: Alfaruqy Maulida Abdillah , Ahsani Dwi Nur , Sudiarto Hilmi Ardian , Yosanto Alfian Novanda 
Published: January 2023

Background:
The elevation of serum uric acid may cause metabolic syndrome and increase systemic inflammation also oxidative stress which are the risk factors for liver disease. Recently, coffee as the most popular drink worldwide could promote antioxidant activity due to some anti-inflammatory effects of some polyphenolic compounds such as cafestol, kahweol, and diterpenes. This study aimed to analyze the profile of liver tissue superoxide dismutase (SOD) in hyperuricemia rats after daily consumption of coffee.

Method:
Four groups, each consisting of 6 rats (Rattus norvegicus), respectively were observed as 1) negative control group; 2) positive control group; 3) caffeinated coffee group; 4) decaffeinated coffee group. Hyperuricemia was conditioned by administering high purine intake into the 2nd until 4th group as much as 140 mg/200gr of weight. Coffee, which is caffeinated and decaffeinated was given to the third and the fourth group respectively with doses 144 mg/200gr of weight. SOD of liver tissue was measured after 30 days of treatment.

Result:
In hyperuricemia rats, daily consumption of coffee shows higher liver SOD levels compared to a positive control group. The average (+SD) of liver SOD each group respectively 79.51(+3.06); 32.24(+3.53); 53.28(+4.49); and 68.03(+4.72). Numeric comparative hypothetic test using one-way ANOVA shows the difference mean between each group was statistically significant (95%CI; p < 0.05).

Conclusion:
Daily consumption of both caffeinated and decaffeinated coffee may reduce oxidative stress in liver tissue of hyperuricemia rats.
PS-B08-3: DILATED CARDIOMYOPATHY MOUSE MODEL AGGRAVATES ACUTE KIDNEY INJURY
Authors: Ishimura Takuya , Ishii Akira , Yamada Hiroyuki , Nakagawa Yasuaki , Ohno Shoko , Ikushima Akie , Sugioka Sayaka , Handa Takaya , Kuwahara Koichiro , Yanagita Motoko , Yokoi Hideki 
Published: January 2023

Objective:
The relation between cardiac and renal diseases is well known, and the concept of the cardio-renal syndrome has attracted much attention in recent years. However, the molecular mechanism of the cardio-renal syndrome is still unclear. In this study, we used αMHC-dominant negative Neuron-Restrictive Silencer Factor (NRSF) transgenic mice (Tg mice), a mouse model of dilated cardiomyopathy with gradually worsening ejection fraction, to elucidate the pathogenesis of acute kidney injury in the setting of chronic heart failure.

Design and Methods:
Sixteen-week-old Tg and wild-type mice were subjected to unilateral nephrectomy and 45-minute ischemia reperfusion injury (IRI) to the remaining kidney, and then the kidneys and hearts were retrieved 72 hours later. The control group were subjected to unilateral nephrectomy without IRI.

Results:
Heart weights were significantly heavier in Tg mice in both control and IRI-treated groups. In the control group, serum creatinine and blood urea nitrogen were unchanged between wild-type and Tg mice. However, serum creatinine and blood urea nitrogen were significantly elevated in Tg mice compared to wild-type mice in the IRI-treated group, and only IRI-treated Tg mice died within 72 hours after IRI (6/14). Furthermore, mRNA expression of Ccl2 and Lcn2 (NGAL) in the whole kidney was significantly elevated in IRI-treated wild-type mice, and was more upregulated in Tg mice. Periodic acid-Schiff staining showed that tubular injuries, such as dilation of tubules, cast formation and tubular atrophy, were exacerbated in IRI-treated Tg mice. In microarray analysis of IRI-treated kidneys from wild-type and Tg mice, several candidate genes were upregulated in Tg mice.

Conclusions:
In dilated cardiomyopathy model mouse, inflammation and histological changes were aggravated after IRI, suggesting that chronic heart failure augments renal impairment in acute kidney injury.
PS-C17-1: PERIPHERAL MICROVASCULAR DYSFUNCTION IN SUBJECTS WITH TYPE2 DIABETES(T2DM) IN ACCORDANCE WITH ABSENCE OR PRESENCE OF CORONARY ARTERY DISEASE.
Authors: Ueda Tomohiro , Teragawa Hiroki , Oshita Chikage , Fujii Yuichi , Nomura Shuichi 
Published: January 2023

Background:
Several studies demonstrated that endothelial function is impaired in patients with T2DM, but no study evaluated vascular parameters in patients with T2DM trough a combined analysis of macro and micro-endothelial function and arterial stiffness indexes. In addition, the difference in vascular parameters between T2DM patients with CAD and without CAD remains unknown. We assessed whether coronary artery disease is associated with impairment of peripheral endothelial function and arterial stiffness indexes in patients with T2DM.

Methods:
We measured vascular function in 219 T2DM subjects (age 68 ± 10 years), including 147 subjects with CAD (CAD group) and 72 subjects without CAD (control group).
Flow mediated vasodilatation (FMD) indicating endothelial function in a conduit artery was measured by ultrasound using a semi-automatic device: UNEXEF18G (UNEX Co. Nagoya, Japan). Reactive hyperemia index (RHI) indicating peripheral endothelial function and Augmentation index (AI) indicating arterial stiffness were measured by peripheral arterial tonometry (EndoPAT 2000). Vascular function tests were measured on the same day.

Results:
RHI and AI was significantly impaired in CAD group (RHI: 2.0 ± 0.7 vs.1.7 ± 0.5 P = 0.012, AI: 30.2 ± 18.1 vs.22.1 ± 19.1 P = 0.043), however FMD had no deference in the two groups. Logistic regression analysis revealed that RHI (odds ratio: 0.44, 95% confidence interval: 0.21–0.94) was an independent predictor for CAD in subjects with T2DM.

Conclusions:
RHI, an acknowledged marker of microcirculatory endothelial function was a more sensitive method in evaluating the risk assessment of CAD in subjects with T2DM.
PS-C17-2: STUDY OF THE ANTIHYPERTENSIVE EFFECTS OF ORAL SEMAGLUTIDE, GLP 1 RECEPTOR AGONIST
Authors: Meguro Shu , Itoh Hiroshi 
Published: January 2023

Objective:
Semaglutide, a GLP1 receptor agonist for diabetes mellitus, has been reported to not only improve blood glucose and body weight, but also to lower blood pressure. In this study, we investigated the effects of oral semaglutide on blood pressure.

Methods:
We compared blood pressure, body weight, and HbA1c before, one month after, and three months after semaglutide administration in patients with type 2 diabetes mellitus attending the first author's outpatient clinic who were started on the oral formulation of semaglutide. We selected the patients for study who were administrated oral semaglutide formulations as new additions to previous therapy or conversions from other oral diabetes medications, and those converted from injectable GLP1 receptor agonists were excluded.

Results:
Baseline clinical characteristics of the subjects were 12 (10 men, 2 women), age 57.9 ± 9.8 years, weight 94.9 ± 16.1 kg, blood pressure 147.9 ± 14.3/84.3 ± 6.0 mmHg, HbA1c 7.4 ± 0.6%. Systolic blood pressure was 138.5 ± 11.8 mmHg for 1 month after treatment and 136.6 ± 9.3 mmHg for 3 months after treatment, showing a significant decrease compared to before treatment (p < 0.05). On the other hand, HbA1c and body weight significantly decreased (p < 0.05) to 6.9 ± 0.9% and 92.2 ± 16.6 kg, respectively, after 3 months of treatment, but no significant change was observed after 1 month of treatment. No significant correlation was observed among the changes in HbA1c and body weight and systolic blood pressure at 1 and 3 months.

Conclusions:
Significant reductions in HbA1c, body weight, and systolic blood pressure were observed with the oral formulation of the GLP1 receptor agonist semaglutide. The decrease in systolic blood pressure was preceded by a decrease in HbA1c and body weight.