Plasma galectin-3 concentration and estimated glomerular filtration rate in patients with type 2 diabetes with and without albuminuria.

This study aimed to investigate the association between galectin-3 concentration and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria. In this cross-sectional study, we examined 334 patients with T2DM. The eGFR was calculated using a creatinine-based formula (eGFRcrea) and a combined creatinine-cystatin C equation (eGFRcrea-cyst). The participants were categorized into two groups based on the urinary albumin-to-creatinine ratio (UACR): patients without albuminuria (UACR < 30 mg/g) and those with albuminuria (UACR ≥ 30 mg/g). Greater concentrations of plasma galectin-3 were associated with lower eGFRcrea-cyst and eGFRcrea levels in patients with and without albuminuria. Plasma galectin-3 concentrations were negatively correlated with eGFRcrea-cyst in patients with normoalbuminuria and albuminuria (γ = - 0.405, P < 0.001; γ = - 0.525, P < 0.001, respectively). Galectin-3 concentrations were significantly associated with eGFRcrea-cyst after adjusting for sex, age, and other confounding factors, including UACR as a categorical or continuous variable in multiple regression analyses (ß = - 0.294, 95% CI - 70.804 to - 41.768, P < 0.001; ß = - 0.265, 95% CI - 65.192 to - 36.550, P < 0.001, respectively). Likewise, when eGFRcrea-cyst was treated in place of eGFRcrea, this result was replicated in the correlation and regression analyses. Galectin-3 concentration was negatively associated with eGFR in patients with T2DM, independent of albuminuria status.

Antimicrobial activities of plant essential oil vapours against Acidovorax citrulli and Xanthomonas campestris on Cucurbitaceae, Brassicaceae and Solanaceae seeds.

AIM: This study was done to develop a seed decontamination treatment for organic seeds against plant pathogens (Acidovorax citrulli and Xanthomonas campestris) using essential oil (EO) vapours without affecting the seeds' germination rate. METHODS AND RESULTS: By using a diffusion assay and determining minimum inhibitory and lethal concentrations, we screened two EO vapours which were most inhibitory to A. citrulli (cinnamon bark and garlic EO vapours) and X. campestris (onion and garlic EO vapours). After 48 h of exposure to EO vapours at 25°C and 43% or 85% relative humidity (RH), no significant decrease (p > 0.05) in germination rates was observed compared with those of control seeds. It was observed that EO vapour treatment at 25°C and 43% or 85% RH for 48 h caused significant population reductions (p ≤ 0.05) (ca. 0.3-2.6 log colony forming unit/g) compared to those of untreated seeds. CONCLUSION: Applications of EO vapours showed significant (p ≤ 0.05) antimicrobial effects against A. citrulli and X. campestris on both laboratory mediums and plant seeds without decreasing the germination rate of seeds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides useful information for the development of natural seed sterilization treatments using EO vapours.

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria.

AIM: To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. METHODS: We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). RESULTS: In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (ß = -0.309, p < 0.001 and ß = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. CONCLUSION: GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.

Association Between Gastric Emptying Time and Incidence of Cardiovascular Diseases in Subjects With Diabetes.

BACKGROUND/AIMS: Delayed gastric emptying (GE) is associated with high morbidity and mortality in subjects with diabetes. The aim of this study is to investigate associations between GE time and the major cardiovascular events (coronary heart diseases and ischemic stroke) in diabetic subjects with upper gastrointestinal (UGI) symptoms. METHODS: Among 259 subjects with chronic UGI symptoms who underwent gastric emptying study (GES) over 13 years, 122 diabetic subjects without gastric surgery and/or rapid GE were enrolled in this study. We also gathered data about baseline demographics, clinical characteristics, estimated GE half-time (GE T½) and incidence of cardiovascular events following GES. RESULTS: The mean age of subjects was 64.0 ± 17.4 years. There were 86 women and 104 subjects with type 2 diabetes. There were 52 (42.6%) subjects with normal GE, 50 (41.0.%) subjects with mild delayed GE, and 20 (16.4%) subjects with marked delayed GE. During follow-up (median, 207 weeks), cardiovascular events occurred in 7 (13.5%) subjects with normal GE, 4 (8.0%) subjects with mild delayed GE and 7 (35.0%) subjects with marked GE ( P = 0.015). Univariate analysis showed that GE T½ was significantly associated with incidence of cardiovascular events (crude OR, 1.74; 95% CI, 1.12-2.69; P = 0.014). In a multivariate model, association between GE T½ and incidence of cardiovascular events remained statistically significant after adjustment for baseline characteristics and comorbidities (adjusted OR, 1.94; 95% CI, 1.21-3.12; P = 0.006). CONCLUSION: A delay of GE was associated with an increased incidence of cardiovascular events in diabetic subjects with chronic UGI symptoms.

Clinical Characteristics, Causes and Survival in 115 Cancer Patients with Parathyroid Hormone Related Protein-mediated Hypercalcemia.

BACKGROUND: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. METHODS: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed. RESULTS: Of all 115 patients, solid organ malignancies were the most common etiology (98 cases, 85.2%), with squamous cell carcinoma (50 cases, 43.4%), adenocarcinoma (27 cases, 23.4%). Interestingly, hepatocellular carcinoma (HCC; 18 cases, 15.7%) and cholangiocarcinoma (11 cases, 9.6%) were much more common causes than other previous reports. Hematologic malignancy was less common (17 cases, 14.8%), with multiple myeloma (9 cases, 7.8%) and non-Hodgkin's lymphoma (5 cases, 4.3%). Overall median survival was only 37 days. There was significant difference in median survival between two groups (35 days for solid organ malignancy and 72 days for hematologic malignancy; P=0.015). Cox regression analysis identified age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis as independent predictive factors for survival time. CONCLUSIONS: PTHrP-mediated hypercalcemia was most frequently caused by solid organ malignancy. However, HCC and cholangiocarcinoma were important causes of PTHrP-mediated hypercalcemia may be due to geographic differences in cancer incidence in Korean population. Age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis were independent poor predictive factors for survival time.

Transient thyrotoxicosis accompanied by panhypopituitarism caused by ruptured Rathke's cleft cyst.

We describe a rare case of transient thyrotoxicosis secondary to painless thyroiditis accompanied by panhypopituitarism caused by ruptured Rathke's cleft cyst. A 32-year-old man presented with vomiting and diarrhea. Laboratory data showed that he had transient hypercalcemia, primary thyrotoxicosis due to painless thyroiditis and panhypopituitarism. The sellar magnetic resonance imaging showed cystic macroadenoma. He underwent surgical exploration. Histological examination showed a ruptured Rathke's cleft cyst. Our case suggests that, although rare, it is important to recognize the possibility of coexistence of hypopituitarism in patients with primary thyrotoxicosis.

Inhibition of osteoblastic differentiation by warfarin and 18-α-glycyrrhetinic acid.

Anticoagulation therapy with vitamin K antagonists such as warfarin is widely used to prevent and treat stroke in patients with chronic atrial fibrillation or mechanical heart valves. Because vitamin K is an essential factor for ggg-carboxylation of osteocalcin, vitamin K antagonists might cause bone loss. Although the association between warfarin use and bone metabolism is still controversial, several studies show that bone mineral density is decreased and fracture risk is increased with warfarin therapy. Meanwhile, attenuation of gap junctional communication (GJC) by warfarin is reported in rat liver epithelial cells. However, the effect of warfarin on osteoblasts, in which GJC is important for osteoblastic differentiation, remains unknown. Here we investigated whether warfarin has an inhibitory effect on osteoblastic differentiation using an osteoblastic cell line (C2C12). Warfarin and 18-α-glycyrrhetinic acid (AGA), which is known as a nontoxic reversible GJC inhibitor, had the same effect on osteoblastic differentiation. Warfarin and AGA inhibited the bone morphogenetic protein (BMP)2-induced mRNA levels of alkaline phosphatase (ALP), collagen I α1, osteocalcin (OC) and osterix, which are specific markers for osteoblastic differentiation, in a dose-dependent manner. Moreover, the activities of OC- and ALP-luciferase reporters, which are induced by BMP2, and the transcriptional activity of Runx2 on OC and ALP promoters were inhibited by warfarin and AGA. The amount and activity of ALP induced by BMP2 were also decreased by warfarin and AGA. These results suggest that warfarin and AGA, a GJC inhibitor, have an inhibitory effect on osteoblastic differentiation.

Spontaneous rupture of a functioning adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis, and it can be classified as either a functional or nonfunctional tumor. Affected patients usually present with abdominal pain or with symptoms related to the mass effect or hormonal activity of the tumor. Several cases of spontaneously ruptured nonfunctional adrenocortical carcinoma have been reported, but no case of a spontaneous rupture of functioning adrenocortical carcinoma has been described. We report a functioning adrenocortical carcinoma that spontaneously ruptured during a work-up.

Ultrasonographic features of papillary thyroid carcinoma in patients with Graves' disease.

BACKGROUND/AIMS: To characterize ultrasonographic findings in papillary thyroid carcinoma (PTC) combined with Graves' disease. METHODS: Medical records and ultrasonographic findings of 1,013 patients with Graves' disease and 3,380 patients without Graves' disease were analyzed retrospectively. A diagnosis of PTC was based on a pathologic examination. RESULTS: The frequency of hypoechogenicity was lower in patients with PTC and Graves' disease than in patients with PTC alone (p < 0.05). The frequency of perinodular blood flow in patients with PTC and Graves' disease was significantly higher than in those with PTC alone (p < 0.05). PTC combined with Graves' disease was characterized by more ill-defined borders and less frequency of overall calcification, punctate calcification, and heterogeneous echogenicity, although the difference was not statistically significant. CONCLUSIONS: Our results suggest that patients with Graves' disease more frequently have atypical PTC findings on ultrasonography.

Hypoglycemia associated with the production of insulin-like growth factor II in a pancreatic islet cell tumor: a case report.

An insulinoma is characterized by endogenous hyperinsulinemia and hypoglycemia. However, it has been reported that insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio occur in patients with hypoglycemia. Although overproduction of Insulin-like growth factor II (IGF-II) by non-islet cell tumors such as large mesenchymal tumors, can cause hypoglycemia, no cases of circulating plasma IGF-II from an islet cell tumor contributing to hypoglycemia have been reported. We report here a rare case of a pancreatic islet tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II, which returned to normal after tumor resection.

Acute onset of steroid psychosis with very low dose of prednisolone in Sheehan's syndrome.

Corticosteroid treatment is frequently associated with psychiatric disturbances. These adverse effects are unusual with low dose of corticosteroid. We describe a patient who rapidly developed a steroid-induced psychosis with very low dose of prednisolone. A 48-year-old woman of Sheehan's syndrome was admitted to hospital with insomnia, euphoric moods and visual hallucinations. She had taken prednisolone (10 mg in the morning and 5 mg at night) for 6 days before admission. These symptoms appeared after first dose of prednisolone. A diagnosis of acute psychosis was made. After improvement of acute psychosis with discontinuation, re-administration of prednisolone at a dose of 2.5 mg per day gave rise to agitation and insomnia. She recovered completely by gradual dosage increase of short-acting corticosteroid after the discontinuation of prednisolone.

The effects of thiazolidinedione treatment on the regulations of aquaglyceroporins and glycerol kinase in OLETF rats.

Aquaporins (AQPs) that transport glycerol in addition to water are classified as aquaglyceroporins (AQP3, 7, 9). AQP7 in the adipose tissue and AQP9 in the liver may coordinately contribute to the increase in hepatic gluconeogenesis in states of insulin resistance. Thiazolidinedione (TZD) has been shown to increase adipose AQP7 and induce glycerol kinase (GlyK) which is nearly absent in adipocytes. In the present study, we analyzed both GlyK and AQP gene expression in adipose and hepatic tissues, and AQP3 in kidneys from Long-Evans Tokushima Otsuka (LETO), Otsuka Long-Evans Tokushima Fatty (OLETF), and rosiglitazone (RSG)-treated OLETF (RSG-OLETF) rats. We also evaluated AQP9 protein expression in cultured human hepatoma cells treated with oleic acid, Wy14643, or RSG. A 2-week RSG treatment increased AQP7 mRNA levels in the mesenteric fat, but not in the epididymal fat of OLETF rats. Rosiglitazone treatment markedly increased GlyK expression in both fat depots, with a greater increase in the mesenteric fat. The magnitudes of GlyK induction by RSG were greater than that of AQP7 in both adipose tissues (P < .05, each). AQP9 and GlyK levels in the liver were not affected by RSG treatment in OLETF rats. Oleic acid and Wy14643 upregulated AQP9 protein expression in cultured human hepatoma cells in a dose-dependent manner. AQP3 mRNA levels tended to increase in the outer medulla of the RSG-OLETF rats. These results indicate that in the adipose tissue TZD has an important role in the glycerol metabolic pathway through the regulation of AQP and GlyK, especially by GlyK induction. Free fatty acids may directly enhance glycerol availability in the liver via the upregulation of AQP9 levels. Renal AQP3 may be related to the fluid retention caused by TZD.