Experimental Use of Calcium Magnesium Acetate, HR-253, 1983

The Iowa Department of Transportation Materials Laboratory personnel announced in early 1982 a process to produce a road deicer consisting of sand grains coated with calcium magnesium acetate (CMA). From that point forward the Iowa DOT began searching for a means of economically producing CMA to their concept. During 1983 and 1984 the first attempts devised for commercially producing CMA were attempted by the W.G. Block Company, Davenport, Iowa, under Iowa Highway Research Board Project HR-253. This first attempt at commercially producing CMA was accomplished by the use of concrete transit mixer equipment. Even though this procedure proved successful in the batch mixing of CMA, the need for higher production rates to reduce the cost per ton still existed. During the fall of 1984, Cedarapids Inc, Cedar Rapids, Iowa, proposed to Iowa DOT personnel the application of their technology to a continuous mixing concept for CMA. Arrangements were made for the continuous test mixing of 60 to 100 tons of CMA/sand deicer. This report covers the production effort, description and results of procedures outlined in Cedarapids Inc's proposal of September 19, 1984. The objectives of this research were: 1. To produce the CMA/sand deicer concept on a continuous mixing basis to Iowa DOT CMA concentration levels. 2. To evaluate the results of preheating the carrying vehicle (sand) prior to CMA ingredient introduction. 3. To analyze the feasibility of production equipment and procedures necessary for portable and/or stationary applications of continuous mixing concepts.

ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention.

BACKGROUND: The contribution of nephrolithiasis-related end-stage renal disease (ESRD) to patients requiring renal replacement therapy has never been specifically evaluated. METHODS: Of the entire cohort of 1,391 consecutive patients who started maintenance dialysis therapy at our nephrology department between January 1989 and December 2000, a total of 45 patients (21 men) had renal stone disease as the cause of ESRD and constitute the study material. Type and cause of renal stone disease was determined in the 45 patients, as well as the change in prevalence of nephrolithiasis-related ESRD with time during this 12-year period. RESULTS: The overall proportion of nephrolithiasis-related ESRD was 3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%; uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant among patients with infection and calcium stones, whereas men were predominant among patients with uric acid or hereditary stone disease. The proportion of patients with nephrolithiasis-related ESRD decreased from 4.7% in the triennial period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 ( P = 0.07). This tendency to a decreasing prevalence mainly was caused by a rarefaction of infection and calcium stones with time, whereas frequencies of uric acid and hereditary stone disease remained essentially unchanged. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD and need for renal replacement therapy. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and proper therapy for conditions that may lead to ESRD through recurrent stone formation and/or parenchymal crystal infiltration.

Neuronal calcium channel mutation in a patient with congenital ataxia and attacks of hemiplegic migraine with cerebral edema

Background: Familial Hemiplegic Migraine (FHM), characterized by a prolonged unilateral hemiparesis, mainly results from mutations in the alpha-1a subunit of the calcium channel gene CACNA1A that can also cause two other dominantly inherited neurological disorders, Episodic Ataxia type 2 (EA2, with sometimes migrainous headaches) and Spinocerebellar Ataxia type 6 (SCA6, late-onset and progressive). A same mutation can have different clinical expression in a family (hemiplegic migraine, migraine-coma, cerebellar ataxia). CACNA1A mutations in FHM are usually missense, leading to gain-of-function, while truncating mutations leading to loss-of-function are usually associated with EA2. Case report: This 9-year-old girl was seen as a baby for hypotonia and transient vertical nystagmus. Her first brain MRI was normal. She evolved as a congenital ataxia, but since the age of two, she had attacks of coma, hemiparesis (either side), partial seizures, dystonic movements and fever. Attacks were initially triggered by minor head bumps, subsequently spontaneous. Brain MRIs in the acute stage always showed transient unilateral hemisphere swelling. Follow-up images revealed atrophic lesions in the temporo-occipital regions and cerebellar atrophy. A prophylactic trial with flunarizine was ineffective. Acetazolamide was recently introduced. Methods: Since our patient shared features of both FHM and EA2, we studied the CACNA1A gene by direct sequencing in the patient's and parents' DNA. Results: We identified an unreported de novo heterozygous deletion of three base pairs (c.4503_4505delCTT) predicting the deletion of one amino acid (p.Phe1502del). The CACNA1A protein contains 4 domains, each formed by six transmembrane segments. The deletion is located in a highly conserved region in segment 6 (S6) of the third domain. Mutations in S6 segments of calcium channels change single-channel conductance and channel selectivity, most resulting in loss-of-function. Outlook: In vitro expression studies of the identified mutation are underway, aiming at understanding its functional consequences and finding an efficient treatment.

Calcium Microdomains Control Exo-Endocytosis of Synaptic-Like Microvesicles in Astrocytes

During the last decade, the discovery that astrocytes possess a nonelectrical form of excitability (Ca21-excitability) that leads to the release of chemical transmitters, an activity called ''gliotransmission'', indicates that these cells may have additional important roles in brain function. Elucidating the stimulus-secretion coupling leading to the exocytic release of chemical transmitters (such as glutamate, Bezzi et al., Nature Neurosci, 2004) may therefore clarify i) whether astrocytes represent in full a new class of secretory cells in the brain and ii) whether they can participate to the fast brain signaling in the brain. Here by using a recently developed approach for studying vesicle recycling dynamics at synapses (Voglmaier et al., Neuron, 2006; Balaji and Ryan, PNAS, 2007) combined with epifluorescence and total internal reflection fluorescence (TIRF) imaging, we investigated the spatiotemporal characteristics of stimulus-secretion coupling leading glutamate exocytosis of synaptic-like microvesicles (SLMVs) in astrocytes. We performed the analysis at both the whole-cell and single-vesicle levels providing the first system for comparing exo-endocytic processes in astrocytes with those in neurons. Both the time course and modalities of secretion in astrocytes present more similarities to neurons then previously expected. We found that 1. the G-protein-coupled receptor (GPCR)-evoked exocytosis reached the maximum on a ms time scale and that 2. ER tubuli formed sub-micrometer domains beneath the plasma membrane in close proximity to exocytic vesicles, where fusion events were spatiotemporally correlated with fast Ca21 events.

Evaluation of Calcium Magnesium Acetate Deicer in Scott County, HR-253, Progress Report, 1987

The field testing of the noncorrosive alternative deicing agent, calcium magnesium acetate is described. Seventy three tons were produced of one part CMA and three parts sand deicer which was field tested on I-280 from I-80 to the Mississippi River (7,000 ADT with 50% trucks). A comparative application was made with one part sand and one part sodium chloride. The study found that CMA deicer required a longer time for the pavement to reach normal conditions, and 20-25% more CMA deicer to provide the desired deicing. It was concluded that the CMA deicer was not as dependable as the sodium chloride deicing agent, and it was more difficult to clean up the equipment for spreading the CMA deicer.

Experimental Macadam Stone Base Des Moines County, HR-175, Construction Report, 1977

In today's era of advanced methods, it is interesting that a centuries-old Roman road-building concept can be the most attractive alternative available. The need for a less expensive road base construction method is very apparent, especially to the county engineer faced with maintaining quality lower traffic volume farm-to-market roads. The revival of the Macadam stone base is one possible solution. Des Moines County believed a Macadam road had excellent possibilities for their particular needs. They proposed a research project designed to eliminate some of the unknown factors of Macadam stone base construction. It is the intent of this research project to develop standardized design procedures and serve as an aid for others in constructing a Macadam base roadway. The Iowa Department of Transportation has published special provisions for the construction of Macadam stone bases that were adopted as the guideline specifications for the research project.

Experimental Use of Calcium Magnesium Acetate, Addendum, HR-253, 1984

The Iowa Department of Transportation Materials Laboratory personnel developed a process to produce a road deicer consisting of sand grains coated with calcium magnesium acetate (CMA). Research project HR-253 was established to explore commercial production of the CMA/sand deicer by an independent contractor. About 60 tons of the deicer was produced at a ready-mix concrete facility and evaluated in the field during the 1983-1984 winter season. The initial contracted production of CMA/sand deicer under research project HR-253 identified two major problems: (1) excessive unreacted lime in the final product, and (2) formation of spherical lumps within the product requiring subsequent size reduction. It was recommended in the HR-253 report that additional deicer be produced as a continuation of the project in order to address these problems and further develop the production process. A contract was negotiated with W. G. Block Co. to produce and deliver 50 tons of additional deicer. This addendum report covers this production effort including descriptions and results of all modifications of equipment and process procedures used.

Reinforced Earth and Stone Columns for Weak Subsoil Conditions, HR-510, 1980

Reinforced Earth is a French development that has been used in the United States for approximately ten years. Virbro-Replacement, more commonly referred to as stone columns, is an outgrowth of deep densification of cohesionless soils originally developed in Germany. Reinforced Earth has applicability when wall height is greater than about twelve feet and deep seated foundation failure is not a concern. Stone columns are applicable when soft, cohesive subsoil conditions are encountered and bearing capacity and shearing resistance must be increased. The conditions in Sioux City on Wesley Way can be summarized as: (1) restricted right of way, (2) fill height in excess of 25 feet creating unstable conditions, (3) adjacent structures that could not be removed. After analyzing alternatives, it was decided that Reinforced Earth walls constructed on top of stone columns were the most practical approach.

Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study.

Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.

Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium.

Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH) influences recovery of the myocardium after transient ischemia. The present study examined the relationship between postischemic injury and activity of PDH and the role of mitochondrial calcium uptake for observed changes in PDH activity. Isovolumically beating isolated rat hearts perfused with erythrocyte-enriched buffer containing glucose, palmitate, and insulin were submitted to either 20 or 35 min of no-flow ischemia. After 20 min of no-flow ischemia, hearts exhibited complete recovery of developed left ventricular pressure (DLVP). The proportion of myocardial PDH in the active state was modestly increased to 38% (compared with 13% in control hearts) without a change in glucose oxidation. In contrast, in hearts subjected to 35 min of no-flow ischemia (which exhibited poor recovery of DLVP), there was marked stimulation of glucose oxidation (+460%; P < 0.01) and pronounced increase in the active fraction of PDH to 72% (P < 0.01). Glycolytic flux was not significantly altered. Ruthenium red (6 microM) completely abolished the activation of PDH and the increase in glucose oxidation. The results indicate that variable stimulation of glucose oxidation during reperfusion is related to different degrees of activation of PDH, which depends on the severity of the ischemic injury. Activation of PDH seems to be mediated by myocardial calcium uptake.

Vancomycin exposure from active calcium sulfate bone filler

Objective: Bone cements and substitutes are commonly used in surgery to deliver antibiotics locally. The objective of this study was to assess the systemic absorption and disposition of vancomycin in patients treated with active calcium sulfate bone filler and to predict systemic concentrations under various conditions. Method: 277 blood samples were taken from 42 patients receiving vancomycin in bone cement during surgery. Blood samples were collected from 3h to 10 days after implantation. Vancomycin was measured by immunoenzymatic assay. Population pharmacokinetic (PK) analysis was performed using NONMEM to assess average estimates and variability of PK parameters. Based on the final model, simulations with various doses and renal function levels were performed. Results: The patients were 64 ± 20 years old, their body weight was 81 ± 22 kg and Cockcroft-Gault creatinine clearance (CLcr) 98 ± 55 mL/min. Vancomycin doses ranged from 200 mg to 6000 mg and implantation sites were hip (n=16), tibia (10) or others (16). Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing prominent variability. Mean clearance (CL) was 3.87 L/h (CV 35%), absorption rate constant (ka) 0.004 h-1 (66%) and volume of distribution (V) 9.5 L. Simulations with up to 8000 mg vancomycin implant showed systemic concentrations exceeding 20 mg/L for 3.5 days in 43% of the patients with CLcr 15 mL/min, whereas 7% of the patients with normal renal function had a concentration above 20 mg/L for 1.1 days. Subtherapeutic concentrations (0.4-4 mg/L) were predicted during a median of 22 days in patients with normal renal function and 4000 mg vancomycin implant, with limited influence of dose or renal function. Conclusion: Vancomycin-laden calcium sulfate implant does not raise toxicity concern. Selection of resistant bacteria, such as Enterococcus and Staphylococcus species, might however be a concern, as simulations show persistent subtherapeutic systemic concentrations during 3 to 4 weeks in these patients.

Leaching of nitrogen, potassium, calcium and magnesium in a sandy soil cultivated with sugarcane

A lysimeter experiment was carried out with sugarcane aiming to evaluate the leaching of nitrogen derived from either urea (15N) or the soil/sugarcane crop residues. The leaching of K+, Ca2+, and Mg2+ was also evaluated. The experiment was a factorial 2x4. The influencing factors were: firstly, the differential addition of two kinds of sugarcane remains to the soil, simulating conditions of cane- plantation renewal after the cane crop harvest, with and without previous straw removal by burning; secondly, four doses of N: 0, 30, 60, and 90 kg ha-1. During the experimental period the total volume of water received by the sugarcane-soil system was 2,015 mm, with 1,255 mm as precipitation and 760 mm as irrigation. The loss of N by leaching from the fertilizer (15N) was not detected. In the first three weeks the largest losses of N by leaching occurred, originating from the soil/sugarcane remains-N. The mean of leached N during the experimental period of 11 months was of 4.5 kg ha-1. The mean losses of K+, Ca2+, and Mg2+ were of 13, 320 and 80 kg ha-1, respectively.

Role of homer 1 proteins in the calcium signaling pathway(s) underlying exo-endocytosis processes of glutamatergic slmvs in astrocytes

The discovery that astrocytes possess a nonelectrical form of excitability (calcium excitability) that leads to the release of chemical transmitters, an activity called gliotransmission, indicates that these cells may have additional important roles in brain function. Elucidating the stimulussecretion coupling leading to the exocytic release of chemical transmitters (such as glutamate, Bezzi et al., Nature Neurosci, 2004) may therefore clarify i) whether astrocytes represent in full a new class of secretory cells in the brain and ii) whether they can participate to the fast brain signaling in the brain. We have recently discovered the existence in astrocytes of functional sub-membrane microdomains of calcium release from the internal stores in response to mGluR5 activation (Marchaland et al., J of Neurosci., 2008). Such sub-plasma membrane calcium microdomains control exocytosis of astrocytic glutamate signaling to neurons. Homer proteins are scaffold proteins controlling calcium signaling in different cellular microdomains, including dendritic spines in neurons (Sala et al., J of Neurosci., 2005). Thus, similarly to dendritic pines, Homer1 could be implicated in the coupling between astrocytic mGluR5 and IP3Rs on the ER. Here, by using a recently developed approach for studying vesicle recycling dynamics at synapses (Voglmaier et al., Neuron, 2006; Balaji and Ryan, PNAS, 2007) combined with epifluorescence and total internal reflection fluorescence (TIRF) imaging, we investigated the involvement of Homer1 proteins in the calcium dependent stimulus-secretion coupling leading glutamate exocytosis of synaptic-like microvesicles (SLMVs) in astrocytes.

Changes in Aortic Pulse Wave Velocity in Hypertension Post-Menopausal Women: Comparison Between Calcium Channel Blocker (CCB) Vs Angiotensin Receptor Blocker (ARB) Regimen

Objective: To compare effects of a non-renin-angiotensin system (RAS) blocker, using a CCB, or a RAS blocker, using an ARB regimen on the arterial stiffness reduction in postmenopausal hypertensive women. Methods: In this prospective study, a total of 125 hypertensive women (age: 61.4_6 yrs; 98% Caucasian; BW: 71.9_14 kg; BMI: 27.3_5 kg/m2; SBP/ DBP: 158_11/92_9 mmHg) were randomized between ARB (valsartan 320mg_HCTZ) and CCB (amlodipine 10mg _ HCTZ). The primary outcome was carotid-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Results: There were no significant differences in baseline demographic data between the two groups. Both treatments effectively lowered BP at the end of the study with similar (p>0.05) reductions in the valsartan (_22.9/_10.9 mmHg) and amlodipine based (_25.2/_11.7 mmHg) treatment groups. Despite a lower (p<0.05 for DBP) central SBP/DBP in the CCB group (_19.2/_10.3 mmHg) compared to the valsartan group (_15.7/_7.6 mmHg) at week 38, a similar reduction in carotid-femoral PWV (_1.7 vs _1.9 m/sec; p>0.05) was observed between both groups. The numerically larger BP reduction observed in the CCB group was associated with a much higher incidence of peripheral edema (77% vs 14%) than the valsartan group. Conclusion: In summary, BP lowering in postmenopausal women led to a reduction in arterial stiffness assessed by PWV measurement. Both regimens reduced PWV at 38 weeks of treatment to a similar degree, despite differences in BP lowering suggesting that the effect of RAS blockade to influence PWV may partly be independent of BP.

Consommation d'aliments riches en calcium dans la population adulte de Suisse romande et du Tessin. [Consumption of calcium-rich food in the adult population of French-speaking Switzerland and of Tessin].

Food intake high in calcium content is important in the development of skeleton and the prevention of osteoporosis. From a public health perspective, it is therefore important to know the dietary calcium intake of a population. Two population surveys in the French and Italian parts of Switzerland (MONICA, 1988-1989, and Geneva, 1991), were combined to study nutritional habits related to calcium intake. A random population sample, aged 35 et 65 years, answered to a 24 hour recall questionnaire, either self-administered (MONICA, cantons of Vaud, Fribourg and Tessin, N = 2734) or by phone (canton of Geneva, N = 475). In the 4 cantons, for the previous day, 60% of participants ate dairy products, particularly whole milk and cheese. They drunk 3-4 dl/day of milk. A significant proportion (10%) of french and italian speaking Swiss did not consume any food high in calcium content. In Geneva, the mean daily calcium intake was 656 mg in men and 489 mg in women. In conclusion 1) eating habits related to calcium intake are similar across cantons; 2) women consume dairy products more frequently than men, but in smaller quantities; 3) about 60% of men and 80% of women do not get the daily amount of calcium recommended for the prevention of osteoporosis.