Revealing a subclinical salt-losing phenotype in heterozygous carriers of the novel S562P mutation in the alpha subunit of the epithelial sodium channel.

OBJECTIVE: Pseudohypoaldosteronism type I (PHA1) is a rare inborn disease causing severe salt loss. Mutations in the three coding genes of the epithelial sodium channel (ENaC) are responsible for the systemic autosomal recessive form. So far, no phenotype has been reported in heterozygous carriers. PATIENTS: A consanguineous family from Somalia giving birth to a neonate suffering from PHA1 was studied including clinical and hormonal characteristics of the family, mutational analysis of the SCNN1A, SCNN1B, SCNN1G and CFTR genes and in vitro analysis of the functional consequences of a mutant ENaC channel. RESULTS: CFTR mutations have been excluded. SCNN1A gene analysis revealed a novel homozygous c.1684T > C mutation resulting in a S562P substitution in the alphaENaC protein of the patient. Functional analysis showed a significantly reduced S562P channel function compared to ENaC wild type. Protein synthesis and channel subunit assembly were not altered by the S562P mutation. Co-expression of mutant and wild-type channels revealed a dominant negative effect. In heterozygote carriers, sweat sodium and chloride concentrations were increased without additional hormonal or clinical phenotypes. CONCLUSION: Hence, the novel mutation S562P is causing systemic PHA1 in the homozygous state. A thorough clinical investigation of the heterozygote SCNN1A mutation carriers revealed increased sweat sodium and chloride levels consistent with a dominant effect of the mutant S562P allele. Whether this subclinical phenotype is of any consequence for the otherwise asymptomatic heterozygous carriers has to be elucidated.

The Deleterious Chemical Effects of Concentrated Deicing Solutions on Portland Cement Concrete, Literature Review, TR-480, 2008

This research project investigated the effects of concentrated brines of magnesium chloride, calcium chloride, sodium chloride, and calcium magnesium acetate on portland cement concrete. Although known to be effective at deicing and anti-icing, the deleterious effects these chemicals may have on concrete have not been well documented. As a result of this research, it was determined that there is significant evidence that magnesium chloride and calcium chloride chemically interact with hardened portland cement paste in concrete resulting in expansive cracking, increased permeability, and a significant loss in compressive strength. Although the same effects were not seen with sodium chloride brines, it was shown that sodium chloride brines have the highest rate of ingress into hardened concrete. This latter fact is significant with respect to corrosion of embedded steel. The mechanism for attack of hardened cement paste varies with deicer chemical but in general, a chemical reaction between chlorides and cement hydration products results in the dissolution of the hardened cement paste and formation of oxychloride phases, which are expansive. The chemical attack of the hardened cement paste is significantly reduced if supplementary cementitious materials are included in the concrete mixture. Both coal fly ash and ground granulated blast furnace slag were found to be effective at mitigating the chemical attack caused by the deicers tested. In the tests performed, ground granulated blast furnace slag performed better as a mitigation strategy as compared to coal fly ash. Additionally, siloxane and silane sealants were effective at slowing the ingress of deicing chemicals into the concrete and thereby reducing the observed distress. In general, the siloxane sealant appeared to be more effective than the silane, but both were effective and should be considered as a maintenance strategy.

Mechanism of urinary calcium regulation by urinary magnesium and pH.

Urinary magnesium and pH are known to modulate urinary calcium excretion, but the mechanisms underlying these relationships are unknown. In this study, the data from 17 clinical trials in which urinary magnesium and pH were pharmacologically manipulated were analyzed, and it was found that the change in urinary calcium excretion is directly proportional to the change in magnesium excretion and inversely proportional to the change in urine pH; a regression equation was generated to relate these variables (R(2) = 0.58). For further exploration of these relationships, intravenous calcium chloride, magnesium chloride, or vehicle was administered to rats. Magnesium infusion significantly increased urinary calcium excretion (normalized to urinary creatinine), but calcium infusion did not affect magnesium excretion. Parathyroidectomy did not prevent this magnesium-induced hypercalciuria. The effect of magnesium loading on calciuria was still observed after treatment with furosemide, which disrupts calcium and magnesium absorption in the thick ascending limb, suggesting that the effect may be mediated by the distal nephron. The calcium channel TRPV5, normally present in the distal tubule, was expressed in Xenopus oocytes. Calcium uptake by TRPV5 was directly inhibited by magnesium and low pH. In summary, these data are compatible with the hypothesis that urinary magnesium directly inhibits renal calcium absorption, which can be negated by high luminal pH, and that this regulation likely takes place in the distal tubule.

The Deleterious Chemical Effects of Concentrated Deicing Solutions on Portland Cement Concrete, Technical Appendices, TR-480, 2008

This research project investigated the effects of concentrated brines of magnesium chloride, calcium chloride, sodium chloride, and calcium magnesium acetate on portland cement concrete. Although known to be effective at deicing and anti-icing, the deleterious effects these chemicals may have on concrete have not been well documented. As a result of this research, it was determined that there is significant evidence that magnesium chloride and calcium chloride chemically interact with hardened portland cement paste in concrete resulting in expansive cracking, increased permeability, and a significant loss in compressive strength. Although the same effects were not seen with sodium chloride brines, it was shown that sodium chloride brines have the highest rate of ingress into hardened concrete. This latter fact is significant with respect to corrosion of embedded steel. The mechanism for attack of hardened cement paste varies with deicer chemical but in general, a chemical reaction between chlorides and cement hydration products results in the dissolution of the hardened cement paste and formation of oxychloride phases, which are expansive. The chemical attack of the hardened cement paste is significantly reduced if supplementary cementitious materials are included in the concrete mixture. Both coal fly ash and ground granulated blast furnace slag were found to be effective at mitigating the chemical attack caused by the deicers tested. In the tests performed, ground granulated blast furnace slag performed better as a mitigation strategy as compared to coal fly ash. Additionally, siloxane and silane sealants were effective at slowing the ingress of deicing chemicals into the concrete and thereby reducing the observed distress. In general, the siloxane sealant appeared to be more effective than the silane, but both were effective and should be considered as a maintenance strategy.

The metabolic syndrome in hypertension: European society of hypertension position statement.

The metabolic syndrome considerably increases the risk of cardiovascular and renal events in hypertension. It has been associated with a wide range of classical and new cardiovascular risk factors as well as with early signs of subclinical cardiovascular and renal damage. Obesity and insulin resistance, beside a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with proinflammatory properties, have been implicated in the pathogenesis. The close relationships among the different components of the syndrome and their associated disturbances make it difficult to understand what the underlying causes and consequences are. At each of these key points, insulin resistance and obesity/proinflammatory molecules, interaction of demographics, lifestyle, genetic factors, and environmental fetal programming results in the final phenotype. High prevalence of end-organ damage and poor prognosis has been demonstrated in a large number of cross-sectional and a few number of prospective studies. The objective of treatment is both to reduce the high risk of a cardiovascular or a renal event and to prevent the much greater chance that metabolic syndrome patients have to develop type 2 diabetes or hypertension. Treatment consists in the opposition to the underlying mechanisms of the metabolic syndrome, adopting lifestyle interventions that effectively reduce visceral obesity with or without the use of drugs that oppose the development of insulin resistance or body weight gain. Treatment of the individual components of the syndrome is also necessary. Concerning blood pressure control, it should be based on lifestyle changes, diet, and physical exercise, which allows for weight reduction and improves muscular blood flow. When antihypertensive drugs are necessary, angiotensin-converting enzyme inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel blockers are preferable over diuretics and classical beta-blockers in monotherapy, if no compelling indications are present for its use. If a combination of drugs is required, low-dose diuretics can be used. A combination of thiazide diuretics and beta-blockers should be avoided.

Investigation into Freezing-Thawing Durability of Low-Permeability Concrete with and without Air Entraining Agent, 2009

The aim of the present study is to investigate the effect of low-permeability concrete, made with reduced water‐to‐binder ratios (w/b) and/or supplementary cementitious materials (SCMs), on the need for air entrainment to achieve freezing‐thawing (F‐T) durability. In the present study, concrete mixes were made with different types of cement (Types I and IP), with or without fly ash replacement (15%), with different water‐to‐binder ratios (w/b =0.25, 0.35, 0.45 and 0.55), and with or without air entraining agent (AEA). All concrete mixtures were controlled to have a similar slump by using different dosages of superplasticizer. The rapid chloride permeability and F-T durability of the concrete samples were determined according to ASTM C1202 and ASTM C666A, respectively. The air void structure of the concrete was studied using the Air Void Analyzer, RapidAir, and porosity tests (ASTM C642). In addition, the general concrete properties, such as slump, air content, unit weight, and 28‐day compressive strength, were evaluated. The results indicate that all concrete mixes with proper air entrainment (ASTM C231 air content ≥ 6%) showed good F‐T resistance (durability factor ≥85%). All concrete mixes without AEA showed poor F‐T resistance (durability factor < 40%), except for one mix that had very low permeability and high strength. This was the concrete made with Type IP cement and with a w/b of 0.25, which had a permeability of 520 coulombs and a compressive strength of 12,760 psi (88 MPa). There were clear relationships between the F‐T durability and hardened concrete properties of non–air entrained concrete. However, such relationships did not exist in concrete with AEA. For concrete with AEA, good F‐T durability was associated with an air void spacing factor ≤ 0.28 mm (by AVA) or ≤ 0.22 mm (by RapidAir).

Insulin-Like growth-factor 1 myocardial expression decreases in chronic alcohol consumption

Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 1820 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis. Results Body weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls. Conclusions Chronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors.

Abnormal meiotic behavior in three species of Crotalaria

The objective of this work was to compare the meiotic behavior and pollen grain viability of three species of Crotalaria. Slides for meiotic analysis were prepared by the air-drying technique. Pollen grain viability was measured by three staining procedures (Alexander's solution, tetrazolium chloride and fluorescein diacetate) and in vitro germination in a sucrose solution. Eight bivalents were observed, confirming previous reports on populations from other regions of Brazil, as well as from other countries. All species showed abnormal meiotic behavior as follows: in Crotalaria micans, cytomixis and abnormal chromosome pairing in diakinesis; in C. spectabilis, abnormal chromosome pairing in diplotene; in C. zanzibarica, shrunk nuclei in leptotene and zygotene. Pollen grains of all three species show low viability, which may be associated with the irregularities of the meiotic behavior.

05021-008 Clear Creek Watershed Final Report Report

The Iowa County Soil and Water Conservation District is applying on behalf of the unincorporated community of Conroy to construct a wastewater collection and treatment system to assist in the cleanup and protection of the Clear Creek Watershed. Conroy sits at the headwaters of Clear Creek. Monitoring of the watershed has shown consistently high levels of E.coli bacteria and chloride near the upper end of the creek. In addition, toilet paper and fecal material have been observed on numerous occasions. These are obvious health threats to the residents of the watershed. The monitoring of the watershed, coupled with lab analysis, suggest septic inputs are negatively impacting the headwaters of Clear Creek. A new sewer system for the community of Conroy will eliminate illegal discharges into the creek and be the first step in the overall protection of the watershed and the water quality therein.

Protection of Structural Concrete Substructures, Construction Report, HR-220, 1981

It is the objective of this project to determine, via field tests, the long term effectiveness of several available systems as their ability to protect concrete surfaces against the intrusion of chloride ions. Early concepts of this project included utilizing personnel from several offices within the Highway Division of the Iowa Department of Transportation. Cooperation and coordination with regularly scheduled activities were considered imperative. A meeting for this purpose was held on April 16, 1980. This meeting was attended by the investigators, Mr. Bernard C. Brown, Office of Materials, Mr. Richard Merritt, District 6 Materials Engineer, Mr. John Saunders, District 6 Maintenance Engineer, and Mr. James Phinney, Resident Maintenance Engineer.

Laboratory Investigation of Bridge Strip Seal Joint Termination Details, SPR RB08-014, 2016

Bridge expansion joints, if not properly designed, constructed, and maintained, often lead to the deterioration of critical substructure elements. Strip seal expansion joints consisting of a steel extrusion and neoprene gland are one type of expansion joint and are commonly used by the Iowa Department of Transportation (DOT). Strip seal expansion joints are susceptible to tears and pull outs that allow water, chlorides, and debris to infiltrate the joint, and subsequently the bearings below. One area of the strip seal that is particularly problematic is where it terminates at the interface between the deck and the barrier rail. The Iowa DOT has noted that the initial construction quality of the current strip seal termination detail is not satisfactory, nor ideal, and a need exists for re-evaluation and possibly re-design of this detail. Desirable qualities of a strip seal termination detail provide a seal that is simple and fast to construct, facilitate quick gland removal and installation, and provide a reliable, durable barrier to prevent chloride-contaminated water from reaching the substructure. To meet the objectives of this research project, several strip seal termination details were evaluated in the laboratory. Alternate termination details may not only function better than the current Iowa DOT standard, but are also less complicated to construct, facilitating better quality control. However, uncertainties still exist regarding the long-term effects of using straight-through details, with or without the dogleg, that could not be answered in the laboratory in the short time frame of the research project.

A Different Perspective for Investigation of PCC Pavement Deterioration, HR-2074, Interim Report, 1996

Many early Iowa Portland Cement Concrete (PCC) pavements provided good performance without deterioration for more than 50 years. In the late 1950's, Iowa was faced with severe PCC pavement deterioration called D cracking due to crushed limestone containing a bad pore system. Selective quarrying solved the problem. In 1990, cracking deterioration was identified on a three year old US 20 pavement in central Iowa. The coarse aggregate was a crushed limestone with an excellent history of performance in PCC pavement. Examination of cores showed very few cracks through the coarse aggregate particles. The cracks were predominately confined to the matrix. A high resolution, low vacuum Hitachi Scanning Electron Microscope (SEM) with an energy dispersion detector was used to investigate the deterioration. Subsequent evaluation identified very little concentration of silica gel (silicon-Si), but did identify substantial amounts of sulfur-s and aluminum-Al (assumed to be ettringite) in the air voids. Some of these voids have cracks radiating from them leading us to conclude that the ettringite filled voids were a center of pressure causing the crack. The ettringite in the voids, after being subjected to sodium chloride (NaCl) brine, initially swells and then dissolves. The research has led to the conclusion that the premature deterioration may be due to ettringite and may have been mistakenly identified as Alkali-Silica reactivity (ASR).

Accuracy profile validation of a new analytical method for butane measurement using headspace-gas chromatography-mass spectrometry.

The aim of our study was to provide an innovative HS-GC/MS method applicable to the routine determination of butane concentration in forensic toxicology laboratories. The main drawback of the GC/MS methods discussed in literature concerning butane measurement was the absence of a specific butane internal standard necessary to perform quantification. Because no stable isotope of butane is commercially available, it is essential to develop a new approach by an in situ generation of standards. To avoid the manipulation of a stable isotope-labelled gas, we have chosen to generate in situ an internal labelled standard gas (C(4)H(9)D) following the basis of the stoichiometric formation of butane by the reaction of deuterated water (D(2)O) with Grignard reagent butylmagnesium chloride (C(4)H(9)MgCl). This method allows a precise measurement of butane concentration and therefore, a full validation by accuracy profile was presented.