Effects of pioglitazone on renal calcium excretion.

Context: Glitazones increase fracture risk in long-term users and in postmenopausal women. Studies have demonstrated deleterious effects of glitazones on bone metabolism. Glitazones also have direct renal tubular effects increasing sodium reabsorption. We hypothesized that glitazones may also regulate renal calcium excretion. Design: In this double-blind, randomized, placebo-controlled, four-way, crossover study, we examined the effects of pioglitazone (45 mg/d for 6 wk) or placebo on renal calcium and phosphate excretion and PTH levels during different sodium intakes in 16 individuals (eight with type 2 diabetes and eight with essential hypertension). Results: Pioglitazone had no effect on corrected plasma calcium and phosphate levels but decreased significantly the alkaline phosphatase and PTH levels. Pioglitazone induced on average a 45% increase in urinary calcium excretion. The fractional excretion of calcium rose to the same extent, suggesting a glomerular filtration rate-independent effect. Sodium intake did not influence the calciuric effect of pioglitazone. Changes in diurnal and nocturnal calciuria were similar. There was no effect of pioglitazone on phosphate excretion. Conclusion: Pioglitazone decreases PTH levels and increases urinary calcium excretion, independently from changes in glomerular filtration rate and from the sodium load, suggesting an inhibitory effect of pioglitazone on the tubular reabsorption of calcium. These effects may contribute to the increased fracture risk with glitazone treatment.

Evaluation of Racial Differences in Seat Belt and Child Restraint Use: A Review of Current Literature, 2004

This report presents the results of a literature review conducted to evaluate differences in seat belt use by race. A literature review was conducted to evaluate overall seat belt use, racial differences in seat belt use, overall child restraint use, racial differences in child restraint use, and information about seat belt and child restraint use specific to Iowa. A number of national studies and regional studies were found and are presented. Mixed results were found as to whether racial differences exist in both seat belt use and child restraint use. However, in the course of the literature review, several items that are of interest to safety in Iowa have emerged, although little data specific to Iowa was encountered. First, national seat belt use appears to be lower among African-Americans than for Caucasians or Hispanics. Second, national crash rates among Hispanics appear to be higher than those for Caucasians, particularly when population and lower vehicle miles traveled (VMT) are considered. One issue that should be considered throughout this literature review is that the Hispanic population may be higher than reported due to large numbers of undocumented persons who do not appear in population estimates, driver’s license, or other databases.

Relationship between macrofauna, mineralogy and exchangeable calcium and magnesium in Cerrado Oxisols under pasture

The objective of this work was to assess the relationship between macrofauna, mineralogy and exchangeable calcium and magnesium in Cerrado Oxisols under pasture. Twelve collection points were chosen in the Distrito Federal and in Formosa municipality, Goiás state, Brazil, representing four soil groups with varied levels of calcium + magnesium and kaolinite/(kaolinite + gibbsite) ratios. Soil macrofauna was collected in triplicate at each collection point, and identified at the level of taxonomic groups. Macrofauna density showed correlation with contents of kaolinite, gibbsite and exchangeable Ca + Mg in the soils. Mineralogy and exchangeable Ca + Mg had significant effects on taxonomic groups and relative density of soil macrofauna. The termites (Isoptera) were more abundant in soils with low exchangeable Ca + Mg; earthworms (Oligochaeta), in soils with high levels of kaolinite; and Hemiptera and Coleoptera larvae were more abundant in gibbsitic soils with higher contents of total carbon.

Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

INTRODUCTION: Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. METHODS: We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. RESULTS: Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. CONCLUSIONS: CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.

Regulation of the transforming growth factor beta-responsive transcription factor CTF-1 by calcineurin and calcium/calmodulin-dependent protein kinase IV.

Transforming growth factor beta (TGF-beta) is a pluripotent peptide hormone that regulates various cellular activities, including growth, differentiation, and extracellular matrix protein gene expression. We previously showed that TGF-beta induces the transcriptional activation domain (TAD) of CTF-1, the prototypic member of the CTF/NF-I family of transcription factors. This induction correlates with the proposed role of CTF/NF-I binding sites in collagen gene induction by TGF-beta. However, the mechanisms of TGF-beta signal transduction remain poorly understood. Here, we analyzed the role of free calcium signaling in the induction of CTF-1 transcriptional activity by TGF-beta. We found that TGF-beta stimulates calcium influx and mediates an increase of the cytoplasmic calcium concentration in NIH3T3 cells. TGF-beta induction of CTF-1 is inhibited in cells pretreated with thapsigargin, which depletes the endoplasmic reticulum calcium stores, thus further arguing for the potential relevance of calcium mobilization in TGF-beta action. Consistent with this possibility, expression of a constitutively active form of the calcium/calmodulin-dependent phosphatase calcineurin or of the calcium/calmodulin-dependent kinase IV (DeltaCaMKIV) specifically induces the CTF-1 TAD and the endogenous mouse CTF/NF-I proteins. Both calcineurin- and DeltaCaMKIV-mediated induction require the previously identified TGF-beta-responsive domain of CTF-1. The immunosuppressants cyclosporin A and FK506 abolish calcineurin-mediated induction of CTF-1 activity. However, TGF-beta still induces the CTF-1 TAD in cells treated with these compounds or in cells overexpressing both calcineurin and DeltaCaMKIV, suggesting that other calcium-sensitive enzymes might mediate TGF-beta action. These results identify CTF/NF-I as a novel calcium signaling pathway-responsive transcription factor and further suggest multiple molecular mechanisms for the induction of CTF/NF-I transcriptional activity by growth factors.

Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE).

OBJECTIVES: Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated.METHODS : A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed.RESULTS : Data from 1376 patients were available. Mean age was 65 +/- 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (<140/90 mm Hg for uncomplicated and <130/80 mm Hg for complicated hypertension) was achieved in 48.9%. Compared to patients with complicated hypertension, BP control was better in patients with uncomplicated hypertension (59.4% vs. 19.2%, p < 0.001). As a monotherapy the most prescribed drug class were angiotensin receptor blockers (ARB, 41%), followed by angiotensin converting enzyme (ACE) inhibitors (21.5%), betablockers (20.8%) and calcium channel blockers (CCB, 10.8%). The most prescribed drug combinations were ARB + diuretic (30.1%) and ACE inhibitors + diuretic (15.3%). 46% were receiving a fixed drug combination. In only 32.7% of patients with uncontrolled hypertension was a change in drug therapy made.CONCLUSION : This representative survey on treated adult hypertensive patients shows that, compared to earlier reports, the control rate of hypertension has improved in Switzerland for uncomplicated but not for complicated, particularly diabetes-associated hypertension. ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy, whereas diuretics and ARBs were the most used for combination therapy.

Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices.

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.

Effets des supplémentations en calcium et vitamine D sur la maladie cardiovasculaire. [Effects of calcium and vitamin D supplementations on cardiovascular disease: review article].

Studies exploring the effect of calcium supplementation on cardiovascular risk suggest that systolic blood pressure decreases with supplementation. A lower calcium intake has been associated with an increased risk of stroke. By contrast, calcium supplementation may increase the risk of myocardial infarction. The effect of vitamin D supplementation on blood pressure is still unclear and no effect of vitamin D supplementation on coronary heart disease or stroke has been clearly demonstrated. There is a lack of randomized clinical trials primarily addressing the effect of these parameters on CVD. Currently, the use of calcium and vitamin D supplementations for the prevention of cardiovascular disease is not justified.

Association of calcemia and serum vitamin D with 24H-urinary calcium excretion in a swiss population-based study

Background: Elevated urinary calcium excretion is associated with reduced bone mineral density. Population-based data on urinary calcium excretion are scarce. We explored the association of serum calcium and circulating levels of vitamin D (including 25(OH)D2 and 25(OH)D3) with urinary calcium excretion in men and women in a population-based study. Methods: We used data from the "Swiss Survey on Salt" conducted between 2010 and 2012 and including people aged 15 years and over. Twenty-four hour urine collection, blood analysis, clinical examination and anthropometric measures were collected in 11 centres from the 3 linguistic regions of Switzerland. Vitamin D was measured centrally using liquid chromatography - tandem mass spectrometry. Hypercalciuria was defined as urinary calcium excretion >0.1 mmol/kg/24h. Multivariable linear regression was used to explore factors associated with 24-hour urinary calcium excretion (mmol/24h) squared root transformed, taken as the dependant variable. Vitamin D was divided into monthspecific tertiles with the first tertile having the lowest value and the third tertile having the highest value. Results: The 669 men and 624 women had mean (SD) age of 49.2 (18.1) and 47 (17.9) years and a prevalence of hypercalciuria of 8.9% and 8.0%, respectively. In adjusted models, the association of urinary calcium excretion with protein-corrected serum calcium was (β coefficient } standard error, according to urinary calcium squared root transformed) 1.125 } 0.184 mmol/L per square-root (mmol/24h) (P<0.001) in women and 0.374 } 0.224 (P=0.096) in men. Men in the third month-specific vitamin D tertile had higher urinary calcium excretion than men in the first tertile (0.170 } 0.05 nmol/L per mmol/24h, P=0.001) and the corresponding association was 0.048 } 0.043, P= 0.272 in women. Conclusion: About one in eleven person has hypercalciuria in the Swiss population. The positive association of serum calcium with urinary calcium excretion was steeper in women than in men, independently of menopausal status. Circulating vitamin D was associated positively with urinary calcium excretion only in men. The reasons underlying the observed sex differences in the hormonal control of urinary calcium excretion need to be explored in further studies.

Current management of true aneurysm of the dorsalis pedis artery.

We describe two cases of true dorsalis pedis artery aneurysms in men referred for pulsatile mass of the dorsal part of the foot. Both aneurysms were resected and grafted with interposition of a short segment of saphenous vein. Histological analysis showed true aneurysm associated with atherosclerosis. To our knowledge, only 12 cases of true dorsalis pedis artery aneurysm have been reported previously. On the basis of our experience and after reviewing the literature, the management of this uncommon pathology was discussed.

Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.