Hypercalcemic effect of insulin in thyroparathyroidectomized alloxan-treated rats

The acute effect of a hypoglycaemic dose of 0.5 U/100 g BW insulin administered intramuscularly on calcium metabolism was investigated in fasted alloxan-treated rats. It was found that the hypercalcaemic effect of insulin was evident only in thyroparathyroidectomized (TPTX) and not in parathyroidectomized (PTX) rats. A subcutaneous administration of 180 MRC mU/100 g BW calcitonin abolished the calcium raising effect of insulin in TPTX rats suggesting a protective role of calcitonin against insulin action in intact rats. In an attempt to elucidate the mechanism of the calcium raising effect of insulin 45Ca administered intravenously was used to indicate the movement of calcium from the plasma pool. Insulin administration delayed the plasma 45Ca disappearance rate but had no effect on bone 45Ca uptake within 120 min. In contrast, insulin administration resulted in a 31% reduction of urinary 45Ca excretion while the urine volume remained unchanged. However, the insulin-induced reduction of urinary calcium excretion could not totally account for the calcium raising effect of insulin in TPTX animals.     

The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism.     

Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate

Uric acid nephrolithiasis (UAN) is a common disease with an established genetic component that presents a complex mode of inheritance. While studying an ancient founder population in Talana, a village in Sardinia, we recently identified a susceptibility locus of approximately 2.5 cM for UAN on 10q21-q22 in a relatively small sample that was carefully selected through genealogical information. To refine the critical region and to identify the susceptibility gene, we extended our analysis to severely affected subjects from the same village. We confirm the involvement of this region in UAN through identical-by-descent sharing and autozygosity mapping, and we refine the critical region to an interval of approximately 67 kb associated with UAN by linkage-disequilibrium mapping. After inspecting the genomic sequences available in public databases, we determined that a novel gene overlaps this interval. This gene is divided into 15 exons, spanning a region of approximately 300 kb and generating at least four different proteins (407, 333, 462, and 216 amino acids). Interestingly, the last isoform was completely included in the 67-kb associated interval. Computer-assisted analysis of this isoform revealed at least one membrane-spanning domain and several N- and O-glycosylation consensus sites at N-termini, suggesting that it could be an integral membrane protein. Mutational analysis shows that a coding nucleotide variant (Ala62Thr), causing a missense in exon 12, is in strong association with UAN (P=.0051). Moreover, Ala62Thr modifies predicted protein secondary structure, suggesting that it may have a role in UAN etiology. The present study underscores the value of our small, genealogically well-characterized, isolated population as a model for the identification of susceptibility genes underlying complex diseases. Indeed, using a relatively small sample of affected and unaffected subjects, we identified a candidate gene for multifactorial UAN.     

Stored-product insects associated with eight feed mills in the midwestern United States

Commercial food- and pheromone-baited pitfall traps and pheromone-baited sticky traps were used during 2003 to survey stored-product insect adults in eight participating feed mills in the midwestern United States. Across the eight feed mills, 27 species of beetles (Coleoptera) and three species of moths (Lepidoptera) were captured in commercial traps. The red flour beetle, Tribolium castaneum (Herbst), was the most abundant insect species captured inside the eight mills. The warehouse beetle, Trogoderma variabile (Ballion), was the most abundant insect species outside the mill and in the mill load-out area. The Indianmeal moth, Plodia interpunctella (Hübner), was the most abundant moth species inside the mill and in the mill receiving area. The Simpson's index of species diversity among mills ranged from 0.39 (low diversity) to 0.81 (high diversity). The types of species found among mills were different, as indicated by a Morisita's index of <0.7, for the majority of mills. The differences in the types and numbers of insect species captured inside, outside, in receiving, and in load-out areas could be related to differences in the types of animal feeds produced and the degree of sanitation and pest management practiced.     

N-acetylcysteine with apocynin prevents hyperoxaluria-induced mitochondrial protein perturbations in nephrolithiasis

Diminished mitochondrial activities were deemed to play an imperative role in surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is particularly valuable to delineate the damaging effects of oxidative stress on mitochondrial proteins. The present study was designed to apply large-scale proteomics to describe systematically how mitochondrial proteins/pathways govern the renal damage and calcium oxalate crystal adhesion in hyperoxaluria. Furthermore, the potential beneficial effects of combinatorial therapy with N-acetylcysteine (NAC) and apocynin were studied to establish its credibility in the modulation of hyperoxaluria-induced alterations in mitochondrial proteins. In an experimental setup with male Wistar rats, five groups were designed for 9?d. At the end of the experiment, 24-h urine was collected and rats were euthanized. Urinary samples were analyzed for kidney injury marker and creatinine clearance. Transmission electron microscopy revealed distorted renal mitochondria in hyperoxaluria but combinatorial therapy restored the normal mitochondrial architecture. Mitochondria were isolated from renal tissue of experimental rats, and mitochondrial membrane potential was analyzed. The two-dimensional electrophoresis (2-DE) based comparative proteomic analysis was performed on proteins isolated from renal mitochondria. The results revealed eight differentially expressed mitochondrial proteins in hyperoxaluric rats, which were identified by Matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) analysis. Identified proteins including those involved in important mitochondrial processes, e.g. antioxidant defense, energy metabolism, and electron transport chain. Therapeutic administration of NAC with apocynin significantly expunged hyperoxaluria-induced discrepancy in the renal mitochondrial proteins, bringing them closer to the controls. The results provide insights to further understand the underlying mechanisms in the development of hyperoxaluria-induced nephrolithiasis and the therapeutic relevance of the combinatorial therapy.     

Urinary analysis of nephrolithiasis markers

Renal stone disease is an ancient and common affliction, common in industrialised nations. The causes and incidence of nephrolithiasis are presented. Afterwards, the promoters and inhibitors of renal stone formation analysis in urine are described including enzymatic methods, chromatography, capillary electrophoresis and other techniques. Aspects such as sample collection and storage are also included. The review article includes referenced tables that provide summaries of methodology for the analysis of nephrolithiasis related compounds.     

Heart Block and Acute Kidney Injury Due to Hyperparathyroidism-Induced Hypercalcemic Crisis

We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.     

Demystifying the medical management of nephrolithiasis

Nephrolithiasis is a common problem associated with significant costs to the health care system. Its prevalence continues to increase, particularly in women, which is attributed to changes in diet and lifestyle. The costs associated with the evaluation and management of nephrolithiasis in the United States has been estimated to be $1.83 billion, and, without any intervention, the risk of recurrence is high. This article reviews the management options for nephrolithiasis including a new formulation of potassium citrate, Urocit®-K 15 mEq, that allows for dosing flexibility which can lead to improved compliance and tolerability.Key words: Nephrolithiasis, Standard metabolic evaluation, Hypercalcuria, Struvite stonesThe incidence of nephrolithiasis worldwide is approximately 1%. In the United States, the prevalence has increased from 3.2% in the 1970s to 5.2% in the 1990s.¹ A recent study suggests that the prevalence of stone disease continues to rise, particularly in women, thought to be due to changes in diet and lifestyle.² The costs associated with the evaluation and management of nephrolithiasis in the United States has been estimated to be $1.83 billion.³ The recurrence rates for stone disease are high. After an initial stone, there is a 30% to 50% chance of forming a second stone within 5 years.Given the high recurrence rate after a first time stone episode, an initial metabolic evaluation to search for underlying causes of nephrolithiasis is warranted. In patients presenting with a single stone episode, a risk assessment should be made to determine the extent of the evaluation (Figure 1). There are a number of factors associated with increased risk of recurrent stone formation (4 Patients with any of these risk factors should be considered at risk and should undergo a standard metabolic evaluation (SME) (Open in a separate windowFigure 1Algorithm for diagnostic evaluation.

Table 1

Risk Factors for Stone Development

A genetic polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR) is associated with stone multiplicity in calcium nephrolithiasis

Calcium nephrolithiasis is one of the most common causes of renal stones. While the prevalence of this disease has increased steadily over the last 3 decades, its pathogenesis is still unclear. Previous studies have indicated that a genetic polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR) is associated with the total serum calcium levels. In this study, we collected DNA samples from 480 Taiwanese subjects (189 calcium nephrolithiasis patients and 291 controls) for genotyping the CASR gene. Our results indicated no significant association between the CASR polymorphism (rs17251221) and the susceptibility of calcium nephrolithiasis. However, we found a significant association between rs17251221 and stone multiplicity. The risk of stone multiplicity was higher in patients with the GG+GA genotype than in those with the AA genotype (chi-square test:P = 0.008;odds ratio  =  4.79;95% confidence interval, 1.44–15.92;Yates'' correction for chi-square test:P = 0.013). In conclusion, our results provide evidence supporting the genetic effects of CASR on the pathogenesis of calcium nephrolithiasis.     

Dictyostelid cellular slime molds associated with grasslands of the central and western United States

Dictyostelid cellular slime molds (dictyostelids) associated with grassland ecosystems of the central and western United States were investigated at nine sites that included examples of the three major ecological types of grasslands (tall grass, mixed grass and short grass) generally recognized for the region. Samples of soil/humus collected from each site were examined with the Cavender method of isolating dictyostelids. For each of those six sites with well developed gallery forests present, an additional set of forest soil/humus samples was collected. A more intensive sampling effort was carried out at one site (Konza LTER) to assess the possible effects of burning and grazing on dictyostelid diversity and density. Twelve species of dictyostelids were recovered from grassland sites, whereas gallery forest sites yielded only nine species. Four cosmopolitan species (Dictyostelium giganteum, D. mucoroides, D. sphaerocephalum and Polysphondylium pallidum) were represented by the greatest densities of clones, with D. sphaerocephalum particularly common. The general pattern across all sites was that both species richness and density of dictyostelids decreased with decreasing precipitation. Samples collected from ungrazed grassland plots yielded higher numbers of both species and clones as compared to grazed plots, and the general pattern was for both values to increase as the interval between fires increased. For numbers of clones this correlation was statistically significant.     

Root-infecting fungi associated with a decline of longleaf pine in the southeastern United States

A 35-year-old longleaf pine stand exhibited trees in various stages of decline. A study was conducted to determine root-infecting fungi and other abnormalities associated with varying degrees of crown symptoms. A four-class crown symptom rating system was devised according to ascending symptom severity. Leptographium procerum and L. terebrantis were significantly associated with increasing crown symptom severity. Heterobasidion annosum was also isolated in higher frequency as crown symptoms increased. Also, evidence of insects on roots increased as did amount of resinosis observed. Edaphic and silvicultural factors may interact with these pathogens and insects to pose a pathological limitation on longer-term management objectives. Further research is needed to determine relationships among various edaphic, silvicultural, and biological factors associated with the decline syndrome on this site. This revised version was published online in June 2006 with corrections to the Cover Date.