Malnutrition- inflammation- atherosclerosis (MIA) syndrome associates with periodontitis in end-stage renal disease patients undergoing hemodialysis: a cross-sectional study.

Malnutrition-inflammation-atherosclerosis (MIA) syndrome is a significant risk factor for mortality in patients undergoing hemodialysis. This study aimed to investigate the association between MIA syndrome and oral health status in hemodialysis patients. A cross-sectional study was conducted on 254 hemodialysis patients. Comprehensive medical and dental examinations were performed. Three components were included to define MIA syndrome: Geriatric Nutritional Risk Index, serum high-sensitivity C-reactive protein, and history of cardiovascular events as indicators of malnutrition, inflammation, and atherosclerosis, respectively. The association of MIA syndrome components with periodontitis and occlusal support was examined by multiple-ordered logistic regression analysis. Of 254 participants, 188 (74.0%) had at least one component of MIA syndrome. After adjusting for possible confounding factors, severe periodontitis was significantly associated with presence of more components of MIA syndrome (odds ratio [OR]: 2.64, 95% confidence interval [CI], 1.44-4.84, p = 0.002) and inflammation and malnutrition components (OR: 2.47 and 3.46, 95% CI 1.16-5.28 and 1.70-7.05, p = 0.020 and 0.001). On the other hand, occlusal support, evaluated by Eichner index, was not significantly associated with MIA syndrome or any of its components. In conclusion, periodontitis is associated with MIA syndrome, particularly with inflammation and malnutrition in hemodialysis patients, independent of occlusal support.

Gut Microbiome and Microbiome-Derived Metabolites in Patients with End-Stage Kidney Disease.

The composition of the gut microbiome is altered in patients with chronic kidney disease (CKD). Dysbiosis leads to decreased levels of stool organic acids (OAs) and systemic inflammation, followed by accumulation of uremic toxins (UTs) and the development of end-stage kidney disease (ESKD). We assessed the relationship between the microbiome and UT levels or the development of ESKD by comparing patients undergoing hemodialysis (HD) and those with normal renal function (NRF). This cross-sectional study recruited 41 patients undergoing HD and 38 sex- and age-matched patients with NRF, and gut microbiome, levels of plasma UTs, inflammatory markers, and stool OAs were compared. The indices of beta-diversity differed significantly between patients with NRF and those undergoing HD, and between patients undergoing HD with and without type 2 diabetes. The levels of stool total OA, inflammatory markers, and UTs differed significantly between the patients with NRF and those undergoing HD. The combined main effects of type 2 diabetes and kidney function status were accumulation of indoxyl sulfate and p-cresyl sulfate. The relative abundances of Negativicutes and Megamonas were associated with development of ESKD and with the levels of UTs, even after adjustment for factors associated with the progression of ESKD. The present study indicates that the gut environment differs between patients with NRF and those undergoing HD and between patients undergoing HD with and without type 2 diabetes. Moreover, ESKD patients with diabetes accumulate more UTs derived from the gut microbiome, which might be associated with cardio-renal diseases and poor prognosis.

Association of type 2 diabetes with periodontitis and tooth loss in patients undergoing hemodialysis.

BACKGROUND: Limited evidence are available regarding the influence of diabetes on periodontitis in hemodialysis patients, although the association between diabetes and periodontal disease is well-known. OBJECTIVE: This study aimed to investigate the influence of type 2 diabetes mellitus (T2D) and its control level on periodontal disease and the number of missing teeth in patients undergoing hemodialysis. SUBJECTS AND METHODS: A single-center cross-sectional study was conducted on 246 Japanese patients with end-stage renal disease undergoing hemodialysis. Comprehensive medical and dental examinations were performed. The association between severity of periodontitis and T2D was examined by multiple ordered logistic regression analysis. A multiple linear regression model was fitted to assess the association of periodontal probing depth (PPD) ≥4 mm and the number of missing teeth with T2D (n = 125). A subgroup analysis involving only the patients with T2D was performed to investigate the factors associated with missing teeth among them. RESULTS: After adjusting for confounders, the classification of periodontitis severity was significantly advanced in patients with T2D (odds ratio: 1.64, 95% confidence interval [CI]: 1.02-2.65, p = 0.04). The proportion of PPD≥4 mm sites and the number of missing teeth was significantly associated with T2D (coefficient: 4.1 and 5.7, 95% CI: 0.2-8.0 and 3.4-8.0, p = 0.04 and <0.001, respectively). Subgroup analysis of T2D patients revealed that glycoalbumin levels (coefficient: 0.4, 95% CI: 0.03-0.80, p = 0.03), but not hemoglobin A1c levels (coefficient: 0.8, 95% CI: -1.0-2.7, p = 0.37), were significantly associated with the number of missing teeth. CONCLUSION: T2D was significantly associated with periodontitis and the number of missing teeth in hemodialysis patients. Moreover, it is first documented that poor glycemic control, as determined by glycoalbumin levels, was significantly associated with the number of missing teeth in hemodialysis patients with T2D.

Linagliptin Inhibits Interleukin-6 Production Through Toll-Like Receptor 4 Complex and Lipopolysaccharide-Binding Protein Independent Pathway in vitro Model.

PURPOSE: Lipopolysaccharides (LPS) induce inflammation by binding to the Toll-like receptor (TLR) 4 complex, including LPS-binding protein (LBP). The anti-inflammatory effects of linagliptin in LPS-induced inflammation in the TLR4-independent pathway have not been examined before. We examined the anti-inflammatory effects of linagliptin in the TLR4- and the LBP-independent pathway. METHODS: U937 cells were cultured in the medium supplemented with 10% fetal bovine serum (FBS) and treated with 100 nM phorbol myristate acetate for 48 h. Cells were then left untreated or were treated with 10 µg/mL anti-TLR4 antibodies alone or in combination with linagliptin for 1 h in media supplemented with or without 10% FBS. The cells were divided into 5 groups: a) control cells (untreated) b) cells treated with LPS c) cells treated with 10 µg/mL anti-TLR4 antibodies d) cells treated with LPS and 10 µg/mL anti-TLR4 antibodies and e) cells treated with LPS, 10 µg/mL anti-TLR4 antibodies, and linagliptin. The LPS concentrations used were 50 pg/mL or 100 pg/mL for cells treated in the presence of 10% FBS and 100 pg/mL or 1 µg/mL for cells treated in the absence of FBS. Linagliptin concentrations of 1 nM, 10 nM, and 100 nM were used for treatment. The supernatants were analyzed for interleukin (IL)-6 production after 24 h of various treatments. RESULTS: LPS increased IL-6 production compared to the untreated control cells, and anti-TLR4 antibody suppressed LPS-induced increased IL-6 levels. Linagliptin suppressed LPS-induced IL-6 production in a concentration-dependent manner in the presence of FBS. However, only 100 nM linagliptin could suppress LPS-induced IL-6 production in the absence of FBS. CONCLUSION: Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment after LPS induction in an experimental model of TLR4 inhibition by anti-TLR4 antibodies. Our results showed that linagliptin may inhibit inflammation through multiple mechanisms centered around the TLR-4-mediated pathway.

Survey of actual conditions of erythema marginatum as a prodromal symptom in Japanese patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. METHODS: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. RESULTS: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM. CONCLUSION: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.

Association between circulating tumor necrosis factor receptors and oral bacterium in patients receiving hemodialysis: a cross-sectional study.

BACKGROUND: High levels of tumor necrosis factor (TNF) receptors (TNFRs; TNFR1 and TNFR2), markers of inflammation, have been reported as significant predictors of mortality in hemodialysis patients. Porphyromonas gingivalis is a major pathogenic bacterium involved in periodontitis, which induces systemic inflammation. We investigated the association between the abundance of P. gingivalis in saliva and serum TNFR levels in hemodialysis patients. METHODS: A cross-sectional study was conducted on 121 hemodialysis patients visiting a clinic in the Tokyo metropolitan area. Medical interviews and examinations, comprehensive dental examinations, bacterial examinations for P. gingivalis in saliva, and measurements of circulating TNFR levels were conducted. Multiple linear regression analysis was performed to evaluate the association between the number of P. gingivalis and circulating TNFR levels. RESULTS: TNFR1 and TNFR2 were positively correlated with high-sensitivity C-reactive protein (hsCRP). Severe periodontitis was significantly associated with the number of P. gingivalis in saliva but not serum TNFR levels. The number of P. gingivalis was significantly associated with both TNFR1 and TNFR2 levels in sera after adjusting for age, sex, body mass index, smoking status, history of diabetes, prior cardiovascular disease events, serum levels of hsCRP and albumin, and severity of periodontitis [for TNFR1: coefficient 0.76, 95% confidence interval (CI) 0.14-1.37, p = 0.02; for TNFR2: coefficient 0.95, 95% CI 0.09-1.80, p = 0.03]. CONCLUSION: Circulating TNFR levels are associated with the number of P. gingivalis in saliva after adjusting for relevant clinical factors.

Poor oral hygiene and dental caries predict high mortality rate in hemodialysis: a 3-year cohort study.

The aim of this study was to investigate the impact of oral hygiene, periodontal diseases, and dental caries on all-cause mortality in hemodialysis. This prospective cohort study included 266 patients with end-stage renal disease who were undergoing hemodialysis. Medical interviews, blood biochemical tests, and comprehensive dental examinations including periodontal pocket examination on all teeth and dental plaque accumulation by debris index-simplified (DI-S), were performed. Survival rates were assessed at a 3-year follow-up. Overall, 207 patients were included in the longitudinal analysis, and 38 subjects died during the follow-up period. Cox proportional hazards analysis of the multivariate model demonstrated that the highest tertile of DI-S had a significantly higher risk of all-cause mortality than the lowest two tertiles after adjustment for age, sex, smoking habit, body mass index, diabetes, prior cardiovascular disease, hemodialysis vintage, high sensitivity C-reactive protein, albumin, and number of remaining teeth (hazard ratio, 3.04; 95% confidence interval, 1.50-6.17; p = 0.002). Moreover, the number of decayed teeth significantly increased the hazard ratio to 1.21 (95% confidence interval, 1.06.1.37; p = 0.003). This study suggests that accumulated dental plaque and untreated decay, but not periodontal disease, may be independently associated with all-cause mortality in patients undergoing hemodialysis.

Hemodialysis as a Risk Factor for Ceftriaxone-Associated Pseudolithiasis in Adults.

Ceftriaxone-associated biliary pseudolithiasis is common among children; however, there are only a few reports of pseudolithiasis in adult patients on HD. This retrospective cohort study included 278 adult patients on ceftriaxone therapy from 1 February 2016 to 1 September 2018. Pseudolithiasis was defined as a new development of sludge or stones in the gallbladder within 60 days of ceftriaxone therapy. After excluding patients with preexisting gallstones and a history of cholecystectomy, 113 patients on maintenance HD, and another 98 patients were enrolled as the HD and control group, respectively. Thirteen patients developed pseudolithiasis. Its incidence was significantly higher in the HD group than that in the control group. Multivariate logistic regression analyses showed that development of pseudolithiasis was significantly associated with HD and ceftriaxone dose. Therefore, HD in patients receiving ceftriaxone therapy appears to be associated with a risk of pseudolithiasis. These findings highlight the need for careful follow-up.

Linagliptin Inhibits Lipopolysaccharide-Induced Inflammation Concentration-Dependently And -Independently.

PURPOSE: Dipeptidyl peptidase-4 inhibitors, including linagliptin, prevent inflammation. However, the in vitro effects of linagliptin are unclear. Moreover, although linagliptin inhibits lipopolysaccharide (LPS)-induced inflammation, the anti-inflammatory effects of linagliptin in this context are not concentration-dependent. In the absence of LPS-binding protein (LBP), the pro-inflammatory effects of LPS involve pathways other than the Toll-like receptor (TLR) 4 pathway. Here, we aimed to determine the anti-inflammatory mechanisms of linagliptin in an experimental model in which LBP was added to the medium. METHODS: Human U937 monocytes were cultured at 1 × 106 cells/mL in Roswell Park Memorial Institute medium and differentiated into macrophages using phorbol myristate acetate. All processes were carried out in medium containing 10% fetal bovine serum (FBS). After 48 hrs of culture, we replaced the medium and pretreated the cells with 100, 250, 500, or 2500 nM linagliptin for 1 hr. We exchanged the medium again, and the cells were treated with 1 ng/mL LPS with or without 100, 250, 500, or 2500 nM linagliptin. Interleukin (IL)-6 and LBP in the supernatant, nuclear factor (NF)-κB/p65 in the nucleus, and reactive oxygen species (ROS) in the cells, as important markers of the mechanism of inflammation induction by LPS, were measured using enzyme-linked immunosorbent assay kits. RESULTS: Linagliptin significantly prevented LPS-stimulated IL-6 production and intranuclear NF-κB/p65 levels in a concentration-dependent manner. LPS-induced intracellular ROS levels were significantly decreased by linagliptin at all concentrations. LBP levels were markedly higher in FBS-containing medium than in medium without FBS. However, LBP levels did not change following administration of linagliptin and/or LPS. CONCLUSION: Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment in the context of LPS-induced pro-inflammatory responses. Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms.

Hepcidin-25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate.

BACKGROUND/AIMS: Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key regulators of iron homeostasis. Correlations among serum ferritin, ERFE and HEP-25 levels and improvements in anaemia have not been evaluated after administration of ferric citrate hydrate (FCH). METHODS: This retrospective observational study investigated 24 patients on haemodialysis with both anaemia (haemoglobin (Hb) < 12 g/dL) and hyperphosphatemia (inorganic phosphorus ≥6 mg/dL). The patients who were administered FCH (1500 mg/day) for 12 consecutive weeks and 12 control patients who were administered a phosphate binder other than FCH were included. Correlations among Hb, HEP-25 and ERFE levels were studied. We then stratified the FCH group into two subgroups using the median baseline values of ferritin, HEP-25, ERFE and HEP-25/ERFE ratio to predict whether these markers could serve as prognostic indicators in the treatment of anaemia. RESULTS: In the FCH group, Hb, transferrin saturation, ferritin, HEP-25 and ERFE levels were all significantly increased, while inorganic phosphorus levels, dosage of erythropoietin-stimulating agent, and erythropoietin resistance index were all significantly decreased after drug administration. A significant inverse correlation was apparent between Hb and HEP-25 levels, and a significant positive correlation was seen between Hb and ERFE levels. A significant inverse correlation was found between HEP-25 and serum ERFE levels. Compared with the high HEP-25/ERFE ratio group, only the low HEP-25/ERFE ratio group exhibited significantly increased Hb levels at 12 weeks. CONCLUSION: HEP-25/ERFE ratio could be a novel prognostic marker for increases in Hb levels following FCH administration.

Linagliptin inhibits lipopolysaccharide-induced inflammation in human U937 monocytes.

BACKGROUND: Atherosclerosis and inflammation are more common in patients with diabetes than in patients without diabetes, and atherosclerosis progression contributes to inflammation. Therefore, anti-inflammatory therapy is important for the prognosis of patients with diabetes. Linagliptin is the only bile-excreted, anti-diabetic oral dipeptidyl peptidase-4 (DPP-4) inhibitor. Although the anti-inflammatory effects of DPP-4 inhibitors in vivo and in vitro have been reported, few in vitro studies have examined the effects of linagliptin using monocytes, which play a central role in arteriosclerosis-related inflammation. Herein, we assessed the anti-inflammatory effects of linagliptin in human U937 monocytes. METHODS: U937 cells at densities of 1 × 106 cells/mL were cultured in Roswell Park Memorial Institute medium supplied with 10% fetal bovine serum and treated with 100 nM phorbol myristate acetate for 48 h for differentiation into macrophages. The media were replaced, and the cells were pretreated with 1, 5, 10, 50, and 100 nM linagliptin for 1 h or were left untreated. The media were then replaced again, and the cells were treated with 1 µg/mL lipopolysaccharide (LPS) or 10 nM interleukin (IL)-1ß only, in combination with 1, 5, 10, 50, and 100 nM linagliptin or were left untreated. The extracted media were used to measure IL-6 and tumor necrosis factor (TNF)-α levels using enzyme-linked immunosorbent assay kits. RESULTS: LPS alone significantly increased IL-6 and TNF-α production compared with the control treatment. The treatment of cells with linagliptin at all concentrations significantly inhibited the LPS-stimulated IL-6 and TNF-α production. Meanwhile, IL-1ß alone significantly increased IL-6 production compared with the control treatment. No significant difference in IL-6 production was noted between the cells treated with IL-1ß and simultaneous treatment with IL-1ß and linagliptin. CONCLUSIONS: Linagliptin inhibited LPS-induced inflammation in human monocytic U937 cells.

Gastrorenal shunt: a cause of hyperammonemia.

Gastrorenal shunts may induce hyperammonemia. Portosystemic shunts should be suspected when hyperammonemia occurs in patients with chronic kidney disease.

Clinical Features of Hereditary and Mast Cell-mediated Angioedema Focusing on the Differential Diagnosis in Japanese Patients.

Objective The present study was designed to identify the clinical characteristics that permit the differential diagnosis of hereditary angioedema (HAE) and mast cell-mediated angioedema (Mast-AE) during the first consultation. Methods The medical histories and laboratory data of 46 patients with HAE and 41 patients with Mast-AE were compared. Results The average age of onset in the HAE group (19.8±9.0 years) was significantly lower than that in the Mast-AE group (35.2±12.0 years). The incidence of familial angioedema (AE) in the HAE group (73.9%) was significantly higher than that in the Mast-AE group (9.7%). The frequency of history of AE in the extremities, larynx, or gastrointestinal tract was significantly higher in the HAE group. The frequency of AE episodes of the lips and eyelids was significantly lower in the HAE group. The serum C4 concentration and CH50 titer were lower than the normal limit in 91.3% and 45.6% of the patients in the HAE group, respectively; in Mast-AE group the serum C4 concentration and CH50 titer were significantly lower than the normal limit in 4.8% and 0% of the patients, the difference between the two groups was statistically significant. A C1-inhibitor (C1-INH) activity level of <50% was observed in all of the HAE patients, but none of the Mast-AE patients. The mean serum IgE titer in the HAE group (120.8±130.5 IU/mL) was significantly lower than that in the Mast-AE group (262.2±314.9 IU/mL). Conclusion The parameters within the patients' medical histories, such as the age at the onset of AE, a family history of AE, and the locations of past AE episodes are critical for the successful diagnosis of the disease. Measurements of the C4 and C1-INH activity are very useful for differential diagnosis of HAE from Mast-AE.

The Impact of Human Parvovirus B19 Infection on Heart Failure and Anemia with Reference to Iron Metabolism Markers in an Adult Woman.

A 35-year-old woman with fever, edema and rash was admitted. Pleural effusion and cardiomegaly were observed. A laboratory analysis revealed anemia with iron deficiency and elevated human parvovirus B19 (B19V) immunoglobulin M. The patient's hepcidin-25 and erythroferrone levels were not elevated compared to those observed later in her clinical course. On the other hand, her growth differentiation factor-15 (GDF-15) levels were elevated. She was diagnosed to have heart failure symptoms and anemia with specific iron metabolism abnormalities due to a B19V infection. After providing supportive treatment, the heart failure symptoms disappeared and her anemia had improved. This case emphasizes the need to include a B19V infection in the differential diagnosis when we encounter cases demonstrating reversible heart failure with anemia.

Vitamin E-Coated Dialyzer Inhibits Oxidative Stress.

AIM: To examine the effects of vitamin E-coated dialyzer on oxidative stress in vitro. METHODS: A dialyzer with a synthetic polymer membrane (APS-11SA) and vitamin E-coated dialyzer (VPS-11SA) were connected to a blood tubing line, and U937 cells were circulated in the device. The circulating fluid was collected at 1, 2, 5, 10, 25, and 50 cycles, which are estimated numbers of passes through the dialyzer. Intracellular reactive oxygen species (ROS) production, malondialdehyde (MDA), and Cu/Zn-superoxide dismutase (SOD) were quantified. RESULTS: Intracellular ROS production was increased in the first cycle by APS-11SA and was decreased throughout the experiment by VPS-11SA. Intracellular ROS production in the VPS-11SA device was lower, and MDA levels were decreased. MDA levels were lower during VPS-11SA processing than during APS-11SA processing. Cu/Zn-SOD levels remained unchanged. CONCLUSION: Our results highlight anti-oxidative-stress effects of a vitamin E-coated dialyzer.

Denosumab for Male Hemodialysis Patients with Low Bone Mineral Density: A Case-Control Study.

Denosumab increases bone mineral density (BMD) in patients not receiving hemodialysis therapy. However, limited data are available in the literature concerning the use of denosumab in hemodialysis patients. We treated male hemodialysis patients with low radius BMD with denosumab therapy for 1 year and evaluated its effect on radius BMD. Seventeen patients were treated with denosumab 60 mg every 6 months, and 20 patients were not treated with denosumab (control group). At seven days, the mean corrected calcium level decreased from 9.2 ± 0.5 mg to 8.5 ± 0.5 mg (P < 0.01), and mean serum phosphorus decreased from 5.0 ± 1.3 mg/dl to 4.2 ± 0.9 mg/dl (P < 0.01). At 1 month, the corrected calcium and serum phosphorus levels were 9.2 ± 0.9 mg/dl and 4.0 ± 1.1 mg/dl, respectively. At 1 year, BMD increased by 2.6% ± 4.4% in the denosumab group and decreased by 4.5% ± 7.7% in the control group (P < 0.001). In our observational study, denosumab therapy represents an effective treatment for male dialysis patients with low BMD.

Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report.

BACKGROUND: Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroidism. The danger of health drinks should always be noted. CASE PRESENTATION: A 72-year-old Japanese woman was previously diagnosed with chronic lymphocytic thyroiditis caused by a goiter and had an elevated thyroid-stimulating hormone level (6.56 µIU/ml), a high anti-thyroid peroxidase antibody level (>600 IU/ml), and a high antithyroglobulin level (> 4000 IU/ml) but normal levels of free triiodothyronine (3.08 pg/ml) and thyroxine (1.18 ng/ml). She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 µIU/ml) level and very low triiodothyronine (< 0.26 pg/ml) and thyroxine (0.10 ng/ml) levels. It was determined that for 6 months she had been consuming a processed, solved health drink ("barley young leaf") in amounts of 9 g/day, which included soybean and kale powder extract. Hypothyroidism might be affected by ingredients of health drinks. She discontinued consumption of the health drink immediately and began taking 12.5 µg of levothyroxine. The amount of levothyroxine was gradually increased every 3 days up to 100 µg. At day 61, her thyroid-stimulating hormone level had decreased (6.12 µIU/ml), her free triiodothyronine (2.69 pg/ml) and thyroxine (1.56 ng/ml) levels had increased, and her general condition was improved. Among risky foods lowering thyroid function, some experimental studies have revealed that isoflavones reduce thyroid function. Therefore, we measured the presence of isoflavones in the patient's frozen serum with thin-layer chromatography. After she discontinued consumption of the health drink, two components quickly disappeared, and the other three components gradually decreased. On the basis of developing solvent composition and a positive ferric chloride reaction in thin-layer chromatography experiment, the five ingredients that disappeared or decreased were highly suspected to be soy isoflavones. CONCLUSIONS: This case emphasizes that consuming health drinks that include soy isoflavone powder extracts can lead to severe hypothyroidism.

Rehabilitation improves prognosis and activities of daily living in hemodialysis patients with low activities of daily living.

BACKGROUND: Activities of daily living (ADL) in aged hemodialysis patients decrease by many factors as hemodialysis therapy, various disease-related complications and underlying disease for rehabilitation. But the correlation between low ADL and mortality remains unclear. We assessed the levels of ADL and effects of rehabilitation in hemodialysis patients with low ADL. Moreover, the association between the baseline functional independence measure (FIM) or rehabilitation treatment effects and all-cause mortality were investigated. METHODS: This prospective cohort study included 182 inpatients on maintenance hemodialysis, who underwent rehabilitation for a decline in ADL. Before and after initiating rehabilitation, ADL were assessed using FIM. RESULTS: The total baseline FIM was 65.1±26.9 (motor items: 39.5±18.7; cognitive items: 25.6±10.7). After rehabilitation, the total FIM increased to 77.1±33.1 (motor items: 50.9±24.4; cognitive items: 26.1±10.8). The baseline FIM, presence or absence of FIM increase, and albumin were significantly associated with mortality. Moreover, the mortality hazard ratio in patients with FIM ≤67 and no FIM increase was 20-fold significantly higher than that in patients with FIM ≥68 and FIM increase. The cognitive items and albumin were significantly associated with the rehabilitation effects in multivariate analysis. CONCLUSIONS: Although the FIM decreased by half in hemodialysis patients, rehabilitation improved their FIM (particularly the motor items). The FIM was a novel predictive marker of 3-year mortality in these patients, and an increased FIM after rehabilitation resulted in better prognosis. Moreover, the effectiveness of rehabilitation may depend on maintaining cognitive functions.

Circulating TNF Receptors 1 and 2 Predict Mortality in Patients with End-stage Renal Disease Undergoing Dialysis.

Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P < 0.0001). During follow-up, 88 (27.6%) patients died of any cause (40 [45.5%] died of cardiovascular disease). In the Cox multivariate model, either TNFR but not TNFα remained a significant independent predictor of all-cause mortality (TNFR1: hazard ratio [HR] 2.34, 95% confidence interval [CI], 1.50-3.64; TNFR2: HR 2.13, 95% CI 1.38-3.29) after adjustment for age, prior cardiovascular disease, predialysis systolic blood pressure, and large systolic blood pressure decline during dialysis session. For cardiovascular mortality, significance was only observed in TNFR1 (TNFR1: HR 2.15, 95% CI 1.13-4.10). Elevated TNFRs levels were associated with the risk of cardiovascular and/or all-cause mortality independent of all relevant covariates in patients undergoing haemodialysis.

Linagliptin Has Wide-Ranging Anti-Inflammatory Points of Action in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Because of the potential anti-inflammatory effects, linagliptin, a therapeutic dipeptidyl peptidase-4 inhibitor, is used as an effective drug for diabetic patients for whom inflammation is a prognosis-related factor. We investigated the anti-inflammatory mechanism of linagliptin using seven markers. METHODS: We pretreated human umbilical vein endothelial cells (HUVECs), with linagliptin and lipopolysaccharide (LPS). The cytosolic fractions were evaluated for protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC), ratio of reactive oxygen species (ROS) and Cu/Zn superoxide dismutase (SOD), activator protein 1 (AP-1), and adenosine 3',5'-cyclic monophosphate (cAMP). RESULTS: Linagliptin increased the PKA and PKC activities and the cAMP levels in LPS-treated cells. However, it inhibited LPS-induced PKB phosphorylation, ratio of ROS and Cu/Zn SOD, and LPS-stimulated AP-1 nuclear translocation. CONCLUSION: We reaffirmed the anti-inflammatory and antioxidant effects of linagliptin. These effects might be related to the three protein kinases. Our findings suggest that linagliptin has a wide range of anti-inflammatory effects.