Cutaneous Adverse Events of New Anti-melanoma Therapies: Classification and Management.

Over the past decade, targeted therapies such as BRAF inhibitors, MEK inhibitors and immunotherapies such as anti-CTLA4 and anti-PD1 antibodies have emerged as novel treatments of advanced melanoma. Along with increased use of these therapies, a range of cutaneous adverse events have also emerged, varying from more serious and frequent cutaneous squamous cell carcinoma to mere cosmetic changes such as curly hair or rare severe toxic epidermal necrolysis. Early detection and management of these cutaneous adverse events will aid patients to receive accurate treatment, avoid unnecessary discontinuation of anti-tumour treatment and improve the patient's overall quality of life. This review will describe various cutaneous adverse events of anti-melanoma therapies and its management.

Effect of smoking cessation for 1 year on periodontal biomarkers in gingival crevicular fluid.

BACKGROUND AND OBJECTIVE: The aim of this 12 mo prospective study was to assess the effect of smoking cessation on periodontal tissue without periodontal intervention, using matrix metalloproteinase (MMP)-8, MMP-9 and interleukin (IL)-1ß in gingival crevicular fluid, and nicotine and cotinine in saliva. MATERIAL AND METHODS: Of the 122 male smokers enrolled in a smoking cessation clinic, 11 quitters, nine non-quitters, six oscillators and 13 non-smokers participated in all experiments done at follow-up week 2, and follow-up months 2, 4, 6 and 12. The following were measured: gingival index; dental plaque index and sites of 3.5 mm < probing depth < 5.5 mm using a WHO probe for the full mouth; amounts of MMP-8, MMP-9 and IL-1ß in gingival crevicular fluid of the upper anterior teeth area using enzyme-linked immunosorbent assay; and concentrations of nicotine, cotinine and hydroxycotinine in saliva using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: No significant differences in MMP-8 and MMP-9 in gingival crevicular fluid were detected between smokers, quit-smokers, oscillators and non-smokers for 1 year. Only the amount of IL-1ß showed that smokers (90.14 ± 65.32 pg/mL) had a significantly higher value compared with non-smokers (37.70 ± 40.90 pg/mL), quit-smokers (32.11 ± 40.50 pg/mL) and oscillators (11.90 ± 12.46 pg/mL) at 2 mo follow-up (p = 0.007). IL-1ß had a positive correlation with nicotine (r = 0.351) and the cotinine (r = 0.376), nicotine (r = 0.492) and hydroxycotinine (r = 0.358), and hydroxycotinine (r = 0.413) levels at 2 wk and 4 and 6 mo follow-up, respectively. CONCLUSIONS: This 1-year prospective smoking cessation study without nonsurgical periodontal therapy shows IL-1ß in gingival crevicular fluid could have a positive relationship with the nicotine and cotinine levels in saliva.

Adherence to ketoacids/essential amino acids-supplemented low protein diets and new indications for patients with chronic kidney disease.

BACKGROUND: Low protein diets (LPD) have long been prescribed to chronic kidney disease patients with the goals of improving metabolic abnormalities and postpone the start of maintenance dialysis. METHODS: We reviewed the recent literature addressing low protein diets supplemented with ketoacids/essential aminoacids prescribed during chronic kidney disease and their effects on metabolic, nutritional and renal parameters since 2013. RESULTS: We show new information on how to improve adherence to these diets, on metabolic improvement and delay of the dialysis needs, and preliminary data in chronic kidney disease associated pregnancy. In addition, data on incremental dialysis have been reviewed, as well as potential strategies to reverse protein energy wasting in patients undergoing maintenance dialysis. CONCLUSION: These recent data help to better identify the use of low protein diets supplemented with ketoacids/essential aminoacids during chronic kidney disease.

Food-grade antimicrobials potentiate the antibacterial activity of 1,2-hexanediol.

UNLABELLED: Preservative agents determining the shelf life of cosmetic products must have effective antimicrobial activity while meeting safety requirements for topical use. In this study, we determined the antimicrobial activity of 1,2-hexanediol against several Gram-positive and Gram-negative bacteria. Antimicrobial susceptibility tests have shown that 1,2-hexanediol exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria with MICs of 0·5-2% (v/v). The bactericidal concentration of 1,2-hexanediol was ranging from 1 to 2 × MIC as demonstrated by time-kill curve assay. A membrane depolarization assay showed that 1,2-hexanediol disrupted the cytoplasmic membrane potential. A checkerboard assay indicated that the effective concentration of 1,2-hexanediol was reduced up to 0·25-0·5 × MIC when combined with macelignan and octyl gallate against Gram-positive bacteria. However, this combination was not effective against Gram-negative bacteria. A turbidity reduction assay demonstrated that the combination of a high concentration of 1,2-hexanediol with food-grade antimicrobial compounds could trigger lytic activity towards Bacillus cereus cells. The remaining cell turbidity was 24·6 and 22·2% when 2% of 1,2-hexanediol was combined with 8 mg l(-1) octyl gallate or with 32 mg l(-1) macelignan respectively. This study showed that food-grade antimicrobial compounds may be used in combination with 1,2-hexanediol to increase its efficacy as a preservative agent in cosmetics. SIGNIFICANCE AND IMPACT OF THE STUDY: The antimicrobial activity of 1,2-hexanediol against Gram-positive and Gram-negative bacteria was potentiated with food-grade antimicrobials including xanthorrhizol, macelignan, panduratin A and octyl gallate, which have already been reported to display anti-inflammatory and other beneficial activities related to cosmetics. Therefore, the combination of 1,2-hexanediol and these food-grade antimicrobial agents would have benefits not only for increasing the antimicrobial activity but also in cosmetics use.

HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study.

AIMS/HYPOTHESIS: HbA(1c) variability has been shown to be an independent risk factor for nephropathy in patients with type 1 diabetes. In this study, we aimed to explore the association between HbA(1c) variability and microalbuminuria development in patients with type 2 diabetes. We also intended to test the applicability of serially measured HbA(1c) over 2 years for this risk assessment. METHODS: Between 2003 and 2005, we recruited 821 middle-aged normoalbuminuric individuals with type 2 diabetes and followed them through to the end of 2010. The average follow-up time was 6.2 years. We defined microalbuminuria as a urine albumin to creatinine ratio of 30 mg/g (3.4 mg/mmol) or higher. HbA(1c) variability was calculated by the SD of serially measured HbA(1c). The Cox proportional hazards model was used to evaluate the association between HbA(1c) SD quartile and development of microalbuminuria. RESULTS: The incidence of microalbuminuria for the overall population was 58.4, 58.6, 60.8 and 91.9 per 1,000 person-years for Q1- to Q4-adjusted HbA(1c) SD, respectively (p for trend = 0.042). Compared with patients in Q1, those in Q4 were about 37% more likely to develop microalbuminuria. The HR derived from a series of 2 year HbA(1c) measurements was similar to that from data collection for longer than 4 years. CONCLUSIONS/INTERPRETATION: In addition to mean HbA(1c) values, HbA(1c) variability, even measured as early as 2 years, is independently associated with the development of microalbuminuria in patients with type 2 diabetes.

Immunohistochemical changes of adenomyosis after heat therapy: comparison of radiofrequency myolysis and endoablation.

PURPOSE: To check the pathologic changes of focal adenomyosis after heat therapy using radiofrequency and to evaluate which approach--endometrial ablation or direct heat therapy--is better for adenomyosis. To evaluate whether the timing of the procedure and the menstrual cycle are related to pathologic outcomes after heat therapy. METHODS: This study included nine women who underwent total hysterectomy for adenomyosis (diameter, > or = 6 cm). Six fresh uteri were excised in the midline and subjected to radiofrequency heat therapy at the center of the adenomyomas (direct heat therapy) and three uteri were subjected to endometrial ablation. Thereafter, 1 cm(3) myometrial tissue was obtained at 1 cm, 2 cm, and 3 cm away from the endometrium. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical analysis using antibodies against cytokerain-19 (CK-19), actin, and estrogen receptor/progesterone receptor (ER/PR) was performed to evaluate CK-19 (endometrial epithelium marker), actin (myometrial marker) and ER/PR (checking the state of the menstrual cycle), respectively. RESULTS: After endometrial ablation, cauterized tissues were not noted 2 cm away from the endometrium. All tissues between the endometruim and center of adenomyosis were cauterized after direct heat therapy. During the uterine proliferative phase, unlike the secretory phase, subendometrial layers were cauterized 10 min after direct cauterization. CONCLUSION: Direct heat therapy is more effective than endometrial ablation in adenomyosis, and heat is conducted effectively when the patients are in the proliferative phase.

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells.

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.

Cigarette smoking and proteinuria in Taiwanese men with Type 2 diabetes mellitus.

AIMS: Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. METHODS: Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was > or = 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. RESULTS: Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). CONCLUSIONS: The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control.

Effects of honeybee venom supplementation in drinking water on growth performance of broiler chickens.

The effects of water supplementation of bee venom (BV) on performance, antioxidant activity, and liver function in Arbor Acres broiler chickens were investigated. Hence, 3 experimental treatment groups (control, 0.5 mg/L of BV, and 1 mg/L of BV) were allocated to 3 replicates of 5,000 one-day-old chicks each. The control group was kept on tap water, whereas the other 2 groups were supplied water supplemented with 0.5 and 1 mg of BV, respectively, per liter of drinking water. Broilers were provided ad libitum access to feed for the experimental period of 1 to 28 d of age. Supplementing drinking water with BV significantly increased BW gain at 28 d of age (P < 0.05). The average daily weight gain from d 1 to 28 was increased for birds supplemented with BV compared with control birds. The increase in BW gain was more pronounced with supplementation of 1 mg/L of BV compared with 0.5 mg/L of BV. An improved feed intake was noted in groups supplemented with BV as compared with control chicks. Liver function enzymes, aspartate aminotransferase, and alanine aminotransferase activities including total cholesterol, total protein, albumin, and globulin were not changed by BV supplementation. Tap water supplementation of BV did not alter the number of leukocytes, erythrocytes, heterophils, and lymphocytes. However, the antioxidative activities estimated as a superoxide dismutase-like activity of broiler chicks supplemented with BV was significantly increased (P < 0.05) in comparison with those without BV supplementation. These data indicate a possibility of better broiler performance through BV supplementation under conditions of severe stressful challenges the newly born chicks encounter.

Sewage sludge reduction and system optimization in a catalytic ozonation process.

The main objective of this study was to suggest a feasible, effective process for the reduction of sewage sludge using ozone oxidation catalysed by metal ion. A series of lab-scale experiments was conducted to select a suitable catalyst and its proper dose to achieve optimum sludge reduction. Using a central composite design under response surface methodology (RSM), system optimization with respect to sludge reduction and cost-effectiveness was performed by varying the independent parameters: dosages of ozone and ions. Five metal ions, Mn2+, Fe2+, Zn2+, CU2+, and Al3+1, were tested, and the manganese ion showed the highest sludge reduction, as measured by a decrease in total suspended solids. The ozone/Mn combination achieved approximately twice as much sludge reduction as the ozonation alone. Furthermore, the Mn dose of 10 mg/g-TS (total solids) resulted in the highest sludge reduction efficiency among the different doses, which ranged from 0 to 20 mg-Mn/g-TS. The predicted efficiency of sewage sludge reduction using the RSM was found to agree well with the experimental results, and the statistical analyses predicted optimum ranges for the doses of ozone and Mn ions, taking into account the overall cost for sewage sludge treatment.

Airway changes and prevalence of obstructive sleep apnoea after bimaxillary orthognathic surgery with large mandibular setback.

This study used three-dimensional computed tomography and polysomnography to evaluate the effect of a large mandibular setback on the postoperative pharyngeal airway space and obstructive sleep apnoea (OSA). Twelve patients who underwent bimaxillary surgery for a mandibular setback movement of >9mm were included in this study. Changes in the pharyngeal airway space and polysomnography parameters based on the surgical movements were analyzed. The median mandibular setback movement was 11.08mm. The total pharyngeal, oropharyngeal, and hypopharyngeal volumes, and the retroglossal cross-sectional area were significantly decreased postoperatively (P=0.006; P=0.005; P=0.012; P=0.005, respectively). The apnoea-hypopnoea index (AHI) increased significantly after surgery (P=0.021). There were significant positive correlations between the preoperative inferiorly located hyoid bone and both AHI and respiratory disturbance index (RDI) postoperative (P=0.008 and P=0.027) and between the postoperative inferiorly dislocated retropalatal level and both AHI and RDI postoperative (P=0.002 and P=0.014). Four patients (33.3%) developed new onset OSA postoperatively. Large mandibular setback movements significantly reduced the pharyngeal airway space in the setting of bimaxillary surgery (P=0.006).

Adult liver abscess: characteristics of patients living in rural north-eastern Taiwan.

AIMS: This study aimed to analyse the characteristics of adult liver abscess (LA) patients living in rural townships of Taiwan. PATIENTS AND METHODS: We retrospectively screened the electronic admission records of a rural community hospital located in north-eastern Taiwan from 1 April, 2002 to 30 April, 2006. Relevant data, including subjects' basic characteristics, laboratory findings and infectious microorganisms, were extracted. RESULTS: Fifty-six subjects (mean age: 66.1 +/- 15.9 years; range: 23-94 years) were enrolled; one patient had an amoebic LA and 55 had pyogenic LA. Five subjects died in hospital. Overall, 80.5% of patients complained of having a fever, 87.5% had single abscess, 71.4% had right hepatic lobe involvement and 58.9% underwent invasive drainage. Most subjects (66.1%) did not have diabetes mellitus, 94.6% did not have a hepato-biliary tumour, 73.2% did not have gallstones, 78.6% did not have hepatitis and 87.5% did not have prior hepato-biliary surgery. Klebsiella pneumoniae was the most common infecting microorganism. Previous hepato-biliary surgery and serum creatinine >2.0 mg/dl were significantly more common in patients >or=65 years of age (p = 0.031). Diabetes mellitus was more common in female subjects (p = 0.021). Invasive drainage and single abscess were not significantly correlated to prognosis. DISCUSSION: Adult LA patients living in rural north-eastern Taiwan have different characteristics than patients living in urban areas. Geriatric LA patients should be managed cautiously because of the possibility of renal insufficiency or previous hepato-biliary surgery. Female LA patients should be evaluated for the presence of diabetes mellitus.

Extended septic thrombophlebitis in a patient with duplicated inferior vena cava: case report and review of literature.

Duplication is one of the congenital abnormalities of the inferior vena cava (IVC) and is reported to be associated with deep venous thrombosis (DVT). We report a case who was admitted for carbamazepine-induced toxic epidermal necrolysis. The patient had persistent fever caused by septic thrombophlebitis extending from the left femoral vein to the duplicated left IVC. The fever and thrombosis resolved under combined treatment with antibiotics and anticoagulants, without further complication of symptomatic pulmonary embolism. This is the first case in patient with IVC duplication complicated by DVT induced by septic thrombophlebitis, which was not seen in the nine cases of IVC duplication reported previously.

Enhanced bio-energy recovery in a two-stage hydrogen/methane fermentation process.

A two-stage hydrogen/methane fermentation process has emerged as a feasible engineering system to recover bio-energy from wastewater. Hydrogen-producing bacteria (HPB) generate hydrogen from readily available carbohydrates, and organic acids produced during the hydrogen fermentation step can be degraded to generate methane in the following step. Three strong acids, HCl, H(2)SO(4), and HNO(3), were tested to determine the appropriate pre-treatment method for enhanced hydrogen production. The hydrogen production rates of 230, 290, and 20 L/kg(-glucose)/day was observed for the sludge treated with HCl, H(2)SO(4), and HNO(3), respectively, indicating that the acid pre-treatment using either HCl or H(2)SO(4) resulted in a significant increase in hydrogen production. The fluorescent in situ hybridization method indicated that the acid pre-treatment selectively enriched HPB including Clostridium sp. of cluster I from inoculum sludge. After hydrogen fermentation was terminated, the sludge was introduced to a methane fermentation reactor. This experiment showed methane production rates of 100, 30, and 13 L/kg(-glucose)/day for the sludge pre-treated with HCl, H(2)SO(4), and HNO(3), respectively, implying that both sulfate and nitrate inhibited the activity of methane-producing bacteria. Consequently, the acid pre-treatment might be a feasible option to enhance biogas recovery in the two-stage fermentation process, and HCl was selected as the optimal strong acid for the enrichment of HPB and the continuous production of methane.

Aristolochic acid nephropathy due to herbal drug intake manifested differently as Fanconi's syndrome and end-stage renal failure--a 7-year follow-up.

Aristolochic acid (AA) may reduce glomerular or proximal tubular function, or both. We report a married couple taking AA-containing herbal drugs. The man developed Fanconi's syndrome (FS) whereas his wife reached end-stage renal failure (ESRF). He was a 36-year-old alcoholic cirrhotic patient who had taken the Chinese herbal drugs for 6 years, presenting with muscle weakness and laboratory findings of FS; the renal pathological findings were compatible with the diagnosis of aristolochic acid nephropathy (AAN). His 38-year-old wife, who took a lower cumulative amount of the same herbal drug for a shorter duration, developed advanced renal failure and severe anemia with pathological findings of extensive tubular atrophy, interstitial fibrosis but spared glomeruli. AA-I was detected in one of the herbal drugs. The wife has been on hemodialysis for 7 years, but the husband is still at the stage of slowly progressive chronic renal failure and persistent FS. None of their 5 children ever took the herbal drug, and none had renal problems during follow-up. It is important to trace the history of herbal drug intake in all the family members because of the possibility of sharing of drugs within a family. In addition to the effect of cumulative doses of AAs and the potentially higher susceptibility of females to AAN, the roles of liver cirrhosis and related vasodilators in the protection of the renal interstitium from fibrosis are questions that warrant further study.

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

To characterize the sodium transport defect responsible for salt wasting in obstructive nephropathy, the major sodium transporters in the medullary thick ascending limb (mTAL), the apical Na-K-2Cl cotransporter and the basolateral Na-K-ATPase, were studied in fresh suspensions of mTAL cells and outer medulla plasma membranes prepared from obstructed and untreated kidneys. Oxygen consumption (QO2) studies in intact cells revealed marked reductions in the inhibitory effects of both furosemide and ouabain on QO2 in cells from obstructed, as compared with control animals, indicating a reduction in activities of both the Na-K-2Cl cotransporter and the Na-K-ATPase. Saturable [3H]bumetanide binding was reduced in membranes isolated from obstructed kidneys, but the Kd for [3H]bumetanide was unchanged, indicating a decrease in the number of functional luminal Na-K-2Cl cotransporters in obstructed mTAL. Ouabain sensitive Na-K-ATPase activity in plasma membranes was also reduced, and immunoblots using specific monoclonal antibodies directed against the alpha and beta subunits of rabbit Na-K-ATPase showed decreased amounts of both subunits in outer medullas of obstructed kidney. A significant decrease in [3H]bumetanide binding was detected after 4 h of ureteral obstruction, whereas Na-K-ATPase activity at this time was still not different from control. We conclude that ureteral obstruction reduces the amounts of both luminal Na-K-2Cl cotransporter and basolateral Na-K-ATPase in mTAL of obstructed kidney and that these reductions contribute to the salt wasting observed after release of obstruction.

Quality and effect of single dose versus split dose of polyethylene glycol bowel preparation for early-morning colonoscopy.

BACKGROUND AND STUDY AIMS: The conventional procedure of ingestion of an entire dose of polyethylene glycol solution on the day before early-morning colonoscopy may result in poor bowel preparation. The aim of this study was to evaluate the efficacy and effect of a split-dose ingestion of polyethylene glycol for early-morning colonoscopy. METHODS: A total of 303 age- and sex-matched consecutive individuals presenting for medical check-ups were randomly assigned to receive either 4 L of polyethylene glycol solution with a soft diet on the day before colonoscopy (n = 152; group A), or 3 L of polyethylene glycol solution with a soft diet on the preceding day and then 1 L of the solution on the day of colonoscopy (n = 151; group B). The quality of bowel preparation was evaluated using the Ottawa scale, and the time to cecal intubation and the technical difficulty during the procedure were also recorded. RESULTS: There was no difference in compliance between group A (single-dose) and group B (split-dose). The quality of bowel preparation was better in group B compared with group A. When the participants were categorized according to compliance (good compliance, 116 in group A, 119 in group B; poor compliance, 36 in group A, 32 in group B), the quality of the bowel preparation had a higher score in the good compliance compared with the poor compliance group, and in group B this difference was usually significant. CONCLUSIONS: Split-dose bowel preparation with polyethylene glycol solution provided a better quality preparation than the conventional method for patients undergoing early-morning colonoscopy.

Association of built environment characteristics with adiposity and glycaemic measures.

OBJECTIVE: This study examined the cross-sectional and longitudinal relationships of built environment characteristics with adiposity and glycaemic measures. METHOD: Longitudinal study sample consisted of 4,010 Framingham Heart Study Offspring (baseline: 1998-2001; follow-up: 2005-2008) and Generation Three (baseline: 2002-2005; follow-up: 2008-2011) participants (54.8% women, baseline mean age 48.6 years). Built environment characteristics (intersection density, greenspace, recreation land and food stores) at baseline were collected. Adiposity and glycaemic measures (body mass index [BMI], waist circumference, abdominal subcutaneous and visceral adipose tissue, and fasting plasma glucose) at baseline and changes during 6.4-year follow-up were measured. RESULTS: In cross-sectional models, higher intersection density and food store density (total food stores, fast food restaurants and supermarkets) were linearly associated with higher BMI (all p < 0.05). Higher greenspace was associated with lower BMI, waist circumference, fasting plasma glucose, prevalent obesity and prevalent diabetes (all p < 0.05). Longitudinally, higher intersection density and food store density, and lower greenspace were associated with smaller increases in abdominal visceral adipose tissue (all p < 0.05). Higher densities of intersections, fast food restaurants and supermarkets were associated with smaller increases in fasting plasma glucose (all p < 0.05). CONCLUSIONS: Collectively, built environment characteristics are associated with adiposity and glycaemic traits, suggesting the potential mechanisms by which built environment influences cardiometabolic health.

Endothelin-1 regulates parathyroid hormone expression of human parathyroid cells.

OBJECTIVE: Parathyroid cells synthesize and release endothelin-1 (ET-1). ET-1 displays an in vitro inhibitory effect on basal parathyroid hormone (PTH) secretion and also counteracts PTH hypersecretion stimulated by low calcium. Such effects are further demonstrated in vivo, independent of the changes in calcitonin. We propose that ET-1 may regulate the pathogenesis of uremic hyperparathyroidism. However, this was not directly demonstrated in human parathyroid glands. DESIGN: Hyperplastic parathyroid glands are obtained from the surgical operation for uremic hyperparathyroidism. Cells are isolated by enzyme digestion and treated with ET-1, and are assessed for PTH mRNA expression. PTH in the plasma and the medium is measured by a newly developed method to detect the whole PTH (1-84). PATIENTS: Uremic patients with severe secondary hyperparathyroidism and ultrasonography-proved hypertrophy of parathyroid glands received elective surgical approaches under general anesthesia. The resected glands were immediately taken to the laboratory for fresh isolation. MEASUREMENTS: Following ET-1 treatment, PTH mRNA expression is evaluated by RT-PCR method. ET-1 is detected with radioimmunoassay kit and PTH is measured by a new commercially available Duo PTH kit. RESULTS: ET-1 exhibited a dose-dependent inhibitory effect (from 10(-12) - 10(-7) M) on PTH mRNA expression of parathyroid cells, either in the basal or in the low-calcium-stimulated states. Release of PTH into the medium is also gradually inhibited by the increase in ET-1 concentrations. CONCLUSIONS: Our results demonstrate that ET-1 attenuates PTH mRNA expression in freshly isolated human parathyroid cells, and PTH release is also decreased. This result is consistent with our previously reported in vitro and in vivo experiments.