Influence of the public transportation system on the air quality of a major urban center. A case study: Milan, Italy

A sampling campaign was conducted in the city of Milan, Italy before and during a transportation strike in January 2004. This strike provided a unique opportunity to investigate the influence of public transportation on the air quality in a major metropolitan area. Twenty-four air samples were collected each day around the city on January 2nd, 7th and 9th. The samples were analyzed for methane, carbon monoxide, non-methane hydrocarbons (NMHCs), halocarbons and alkyl nitrates. Significant differences in the mixing ratios were observed among the three days of sampling, with January 2nd showing the lowest concentrations as a result of decreased activity in the city during the holiday season. January 9th showed the highest NMHC concentrations because of increased vehicular activity in the city due to a public transportation strike. This paper investigates the correlation between the increased number of vehicles and decreased air quality because of a reduction in public transportation. Computer simulations were able to reproduce measurements of ozone production during the January 2004 strike and a July 2005 strike. The measurements and simulations suggest that reduced VOC emissions due to the existence of public transportation lowers peak ozone by 11-33% during the summer months. © 2008 Elsevier Ltd. All rights reserved

Osteoblast-Derived FGF9 Regulates Skeletal Homeostasis

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three month old Fgf9OB −/− mice displayed a significant decrease in cancellous bone and bone formation in the distal femur and a significant decrease in cortical thickness at the TFJ. Strikingly, female Fgf9OB −/− mice did not display altered bone mass. Continuous treatment of mouse BMSCs with exogenous FGF9 inhibited mouse BMSC mineralization while acute treatment increased the proliferation of progenitors, an effect requiring the activation of Akt1. Our results suggest that mature OBs are an important source of FGF9, positively regulating skeletal homeostasis in male mice. Osteoblast-derived FGF9 may serve a paracrine role to maintain the osteogenic progenitor cell population through activation of Akt signaling

Chronic Pharmacological and Safety Evaluation of Hematide™, a PEGylated Peptidic Erythropoiesis-Stimulating Agent, in Rodents

Hematide™ is a synthetic peptide-based, PEGylated erythropoiesis-stimulating agent, which is being developed for the chronic treatment of anaemia associated with chronic renal failure. To support the safety of long-term dosing of chronic renal failure patients, a comprehensive toxicology programme was implemented including rat subchronic and chronic studies. Rats were administered 0, 0.1, 1 and 10 mg/kg of Hematide every 3 weeks for 3 months via subcutaneous injection or for 6 months via intravenous injection. The dosing period was followed by a 6-week follow-up period. The primary pharmacology of Hematide resulted in erythroid polycythemia as measured by elevated haemoglobin levels that were time-and dose-dependent. The pharmacology profiles were similar regardless of administration route. For example, for male rats at Day 90, subcutaneous dosing resulted in haemoglobin increases of 2.7, 4.5 and 6.9 g/dl for 0.1, 1 and 10 mg Hematide/kg respectively, compared to 2.8, 5.7 and 7.4 g/dl increases for intravenous dosing. Histopathological changes were related to the prolonged severe polycythemia induced in normocythemic animals administered an erythropoiesis-stimulating agent. The findings included extramedullary haematopoiesis in the spleen and liver, bone marrow hypercellularity and organ congestion. Microscopic findings were reversible, demonstrating a return towards control findings within 6 weeks following cessation of dosing. Systemic exposures, based on both area under the curve (AUC) and maximum concentration (Cmax), were substantially greater for intravenous than subcutaneous administration. No Hematide-specific antibodies were detected. In conclusion, Hematide is a potent erythropoiesis-stimulating agent, and the studies provide support for the safety of clinical development, including chronic dosing, for the treatment of anaemia associated with chronic renal failure

Glycemic Control and Cardiovascular Mortality in Hemodialysis Patients With Diabetes

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0–8.9, 9.0–9.9, and ≥10%, compared with 7.0–7.9% (reference), was 1.06 (95% CI 1.01–1.12), 1.05 (0.99–1.12), and 1.19 (1.12–1.28), respectively, and for time-averaged A1C was 1.11 (1.05–1.16), 1.36 (1.27–1.45), and 1.59 (1.46–1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0–6.9%, HR 1.05 [95% CI 1.01–1.08]; 5.0–5.9%, 1.08 [1.04–1.11], and ≤5%, 1.35 [1.29–1.42]) compared with 7.0–7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175–199, 200–249, 250–299, and ≥300 mg/dL, compared with 150–175 mg/dL (reference), was 1.03 (95% CI 0.99–1.07), 1.14 (1.10–1.19), 1.30 (1.23–1.37), and 1.66 (1.56–1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk

Impact of Race on Hyperparathyroidism, Mineral Disarrays, Administered Vitamin D Mimetic, and Survival in Hemodialysis Patients

Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice-weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (>10 µg/week) had a demonstrable survival advantage over nonblacks (case-mix-adjusted death hazard ratio = 0.87, 95% confidence level 0.83–0.91) compared with those who received lower doses (<10 µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted. © 2010 American Society for Bone and Mineral Research

Cross-sectional study on the prevalence of anemia among rural elderly in Asan

The objective of this study was to assess the prevalence and clinical characteristics of anemia and to define the risk factors for anemia in older Koreans in Asan. From January to February 2002, five hundred sixty two community-dwelling older adults aged over 60 years were selected from a cross sectional study. All subjects underwent laboratory tests, which included a complete blood cell count, reticulocyte, liver and renal functional tests, lipid profiles and iron status tests. The median age was 68.6 years (range, 60-92 years). The mean levels of hemoglobin were 14.4 ± 1.3 g/dL in men and 12.9 ± 1.0 g/dL in women, and the overall prevalence of anemia was 12.5% in all subjects, 10.8% in men and 13.6% in women. The prevalence of anemia was the lowest among age group of 60-69 (10.0%) followed by 70-79 (15.5%), and the highest among age over 80 (20.7%), but the difference was significant only for men. The age difference was more distinct in men than in women (p<0.05). The mean hemoglobin level was significantly lower in the subjects aged over 80 y than those in the 60-69 y group (p<0.05). According to a logistic regression analysis, lower albumin and higher creatinine levels were identified as independent risk factors of anemia among older adults in Asan. In conclusion, the overall prevalence of anemia in our study group was 12.5% and the highest (20.7%) among those aged over 80 y

Parathyroid hormone receptors in GtoPdb v.2021.3

The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [49]) are class B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors. The structure of a long-active PTH analogue (LA-PTH, an hybrid of PTH-(1-13) and PTHrP-(14-36)) bound to the PTH1 receptor-Gs complex has been resolved by cryo-electron microscopy [147]. Another structure of a PTH-(1-34) analog bound to a thermostabilized inactive PTH1 receptor has been obtained with X-ray crytallography [34]

Parathyroid hormone receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [47]) are family B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors