Significant Increase In Serum Research Articles

Bacterial DNA and its consequences in patients with cirrhosis and culture-negative, non-neutrocytic ascites

The detection of bacterial DNA in serum and ascitic fluid (AF) from patients with liver cirrhosis and ascites is interpreted as molecular evidence of intestinal bacterial translocation (BT) and considered sufficient to activate the cellular immune response leading to greater cytokine synthesis. We studied 34 patients with liver cirrhosis and culture-negative, non-neutrocytic ascites [22 patients without bacterial DNA (group I) and 12 patients with bacterial DNA (group II)]. History and clinical examination were done with the following investigations at first admission and followed up for 24 weeks: serum and AF tumour necrosis factor-alpha (TNF-alpha), AF polymorphonuclear leukocytes, AF cultivation and detection of blood and AF bacterial DNA. Serum and AF TNF-alpha were significantly higher in patients with bacterial DNA compared to those without bacterial DNA at first admission [54.5+/-22.56 vs 35.2+/-17.97 pg ml(-1) (P=0.02) and 123.2+/-49.32 vs 82.6+/-29.58 pg ml(-1) (P <0.005), respectively]. These changes became highly significant at the end of follow-up of both groups [119.3+/-27.19 vs 40.2+/-16.08 pg ml(-1) (P <0.001) and 518.8+/-91.11 vs 97.6+/-17.81 pg ml(-1) (P <0.001), respectively]. In group II, there was a significant increase in serum and AF TNF-alpha at the end of follow-up compared to at first admission (P <0.001). The relative risk of death, hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP) was higher in patients with bacterial DNA compared to those without bacterial DNA. We conclude that cirrhotic patients with culture-negative, non-neutrocytic ascites and bacterial DNA have a significantly higher level of serum and AF TNF-alpha and higher risk of HRS, SBP and mortality compared to those without bacterial DNA, suggesting that bacterial DNA and TNF-alpha are implicated in these complications of liver cirrhosis.

Sunbed Radiation Provokes Cutaneous Vitamin D Synthesis in Humans—A Randomized Controlled Trial

We wanted to investigate whether the use of sunbeds with sunlamps emitting mainly UVA and only 0.5% or 1.4% UVB will increase the level of serum 25-hydroxyvitamin D (25(OH)D). In a randomized, controlled, open study on healthy, Caucasian females (> 50 years) sunbed radiation was given as follows: four 6-min sunbed sessions (days 0, 2, 4 and 7) and four 12-min sunbed sessions (days 9, 11, 14 and 16 ) with sunlamps emitting 0.5% UVB (n = 20) or with sunlamps emitting 1.4% UVB (n = 15). The controls (n = 21) had no intervention. Serum levels of 25(OH)D were measured on days 0, 9 and 18 in all three groups. The average increase in serum 25(OH)D from day 0 to day 9 was 12 nmol L(-1) (SD 11 nmol L(-1), P = 0.0002) in the 0.5% UVB group and 27 nmol L(-1) (SD 9 nmol L(-1), P < 0.0001) in the 1.4% UVB group. From day 9 to day 18 a further but not significant increase in serum 25(OH)D of 3 nmol L(-1) (SD 9 nmol L(-1), P = 0.2) in the 0.5% UVB group and 0.6 nmol L(-1) (SD 18 nmol L(-1), P = 0.9) in the 1.4% UVB group was seen. No significant changes were found in the control group. Increasing with UVB dose and exposure time, 37-64% of the sunbed sessions resulted in side effects such as erythema or polymorphic light eruption. The results showed that sunbeds emitting 0.5% and 1.4% UVB increased 25(OH)D serum levels. The increases were dose dependent but reached a plateau after few sessions. Sunbed use as vitamin D source is, however, not generally recommendable due to the well-known carcinogenicity and high frequency of acute side effects.

Parenteral calcium for intensive care unit patients

Hypocalcemia is prevalent among critically ill patients requiring intensive care. Several epidemiological studies highlight a direct association between hypocalcemia and mortality. These data provide the impetus for current guidelines recommending parenteral calcium administration to normalize serum calcium. However, in light of the considerable variation in the threshold for calcium replacement, the lack of evidence to support a causal role of hypocalcemia in mortality, and animal studies illustrating that calcium supplementation may worsen outcomes, a systematic review is essential to evaluate whether or not the practice of calcium supplementation for intensive care unit (ICU) patients provides any benefit. To assess the effects of parenteral calcium administration in ICU patients on the following outcomes: mortality, multiple organ dysfunction, ICU and hospital length of stay, costs, serum ionized calcium concentration, and complications of parenteral calcium administration. We searched The Cochrane Library, MEDLINE, EMBASE, Current Controlled Trials, and the National Research Register. We hand-searched conference abstracts from the Society of Critical Care Medicine, the European Society of Intensive Care Medicine, the American Thoracic Surgery, the American College of Surgeons, the American College of Chest Physicians, the American College of Physicians, and the International Consensus Conference in Intensive Care Medicine. We checked references of publications and attempted to contact authors to identify additional published or unpublished data. Randomised controlled and controlled clinical trials of ICU patients comparing parenteral calcium chloride or calcium gluconate administration with no treatment or placebo. Two reviewers independently applied eligibility criteria to trial reports for inclusion and extracted data. There are no identifiable studies that have evaluated the association between parenteral calcium supplementation in critically ill ICU patients and the following outcomes: mortality, multiple organ dysfunction, ICU and hospital length of stay, costs, and complications of calcium administration. Serum ionized calcium concentration was reported in 5 studies (12 trial arms, 159 participants). These trials showed a small but significant increase in serum ionized calcium concentration after calcium administration. These trials showed considerable statistical heterogeneity and differed extensively in the population studied (adult versus neonate), the indication (hypocalcemia versus prophylaxis) and threshold of hypocalcemia for which parenteral calcium was administered, and the timing of subsequent measurement of serum ionized calcium concentration to the extent that we consider a pooled estimate almost inappropriate. There is no clear evidence that parenteral calcium supplementation impacts the outcome of critically ill patients.

Validation of a commercially available fluorescence-based instrument to evaluate stallion spermatozoal concentration

This study was conducted to determine the response of serum testosterone (T) in male equines (stallions, donkeys and mules) after administering intravenous doses of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing hormone (LH) and saline as a control. The animals were divided into four groups of three each: Group I, 3 ml of 0.95% saline; Group II, 50 μg KP-10; Group III, 2500 IU hCG and group IV, 400 μg LH. The administration of KP-10 and hCG to stallions resulted in a significant increase in serum T concentration at 240 min; whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was significantly higher at 60, 120, and 240 min with LH treatment as compared to pre-dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as compared to the control and hCG concentrations. After 120 and 240 min, T concentrations in mules were higher (p < 0.05) with administration of KP-10, hCG and LH as compared to the control. In conclusion, the administration of KP-10, hCG and LH elevate the serum T concentration in normal male equines. It is suggested that KP-10 may be useful in situations where an increase in T is desired. Further work is required to determine the effect of KP-10 on T in male equids with reproductive abnormalities before it can be used in clinical situations.

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

Chronic renal failure causes left ventricular hypertrophy, but the molecular mechanisms involved remain unknown. We, therefore, investigated whether the mineralocorticoid receptor is implicated in the cardiac hypertrophy observed in uremic rats and whether mineralocorticoid receptor blockade could be protective in chronic renal failure. Experimental groups were: control rats, uremic rats (NPX) with 5/6 nephrectomy (5 weeks), and NPX rats fed with spironolactone for 5 weeks. Systolic blood pressure was increased in both NPX rats and NPX rats fed with spironolactone for 5 weeks. Echocardiography revealed concentric left ventricular hypertrophy in uremia, which was attenuated by spironolactone. Enlarged cardiomyocyte size was observed in both left and right ventricles of NPX rats, an effect that was prevented by spironolactone. Mineralocorticoid receptor antagonism attenuated the increase of ventricular brain natriuretic peptide mRNA levels induced by nephrectomy. Left ventricular gene expressions of aldosterone synthase, mineralocorticoid receptor, and hydroxysteroid dehydrogenase type 2 were the same in the 3 groups, whereas gene expression of the glucocorticoid receptor was significantly diminished in chronic renal failure rats. No significant differences in cardiac aldosterone were observed between control rats and NPX rats, although NPX rats fed with spironolactone for 5 weeks showed increased plasma aldosterone levels. However, a significant increase in serum and glucocorticoid-inducible kinase-1 mRNA expression and protein was present in the NPX group; spironolactone treatment significantly reduced serum and glucocorticoid-inducible kinase-1 mRNA and protein in the left ventricle. Uremic rats exhibited a significant increase of superoxide production and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits expression (NOX-2, NOX-4, and p47(phox)) in the left ventricle, which was prevented by the mineralocorticoid receptor antagonist. Our findings provide evidence of the beneficial effects of spironolactone in cardiac hypertrophy and cardiac oxidative stress in chronic renal failure.

Does presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients?

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03+/-1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42+/-1.06 ng ml(-1); P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60+/-1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89+/-1.43 ng ml(-1); P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86+/-3.64 ng ml(-1)) compared to preoperative level (5.11+/-2.47 ng ml(-1); P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.

National Food-Fortification Program with Folic Acid in Chile

The Chilean Ministry of Health legislated to add folic acid (2.2 mg/100 g) to wheat flour to reduce the risk of neural tube defects (NTD), beginning in January 2000. This policy resulted in a significant increase in serum and red blood cell folate in women of childbearing age 1 year after fortification. The frequency of NTD was studied in all births, both live and stillbirths, in a prospective hospital-based design including 25% of national births during 1999-2000 (prefortification period) and 2001-2002 (postfortification period). During the prefortification period, there was a total of 120,566 newborns, and the NTD rate was 17.1/10,000 births. During the postfortification period (2001-2002) there was a total of 117,704 newborns, and the NTD rate was significantly reduced by 43% to 9.7/10,000 births (RR = 0.57; 95% CI, 0.45 to 0.71). This implies a reduction of 43% in the rate of NTD. The costs per NTD case and infant death averted were 1,200 international dollars (I$) and I$11,000, respectively. The cost per disability-adjusted life year (DALY) averted was I$91, or 0.8% of the country's per capita GDP. On the overall, fortification resulted in net cost savings of I$1.8 million. Fortification of wheat flour with folic acid has proven to be an effective and cost saving strategy for the primary prevention of NTD in a middle-income country in a postepidemiological transition, and in a dramatically short period of time.

Evaluation of some adverse effects of the glycoside convicine in Sprague–Dawley rats

Isouramil (IU) is a glycone of the glycoside convicine isolated from faba beans (Vacia faba L.). Convicine produced a hemolytic crisis termed favism especially in patients deficient in glucose-6-phosphate dehydrogenase. In the present study experiments were performed to investigate the effects of covicine on Sprague–Dawley rats. Three groups of albino rats were used including control, the second and third group were given oral dose of convicine (2 mg 100 g b. wt.−1) for 15 and 30 days, respectively. Convicine produced significant decreases in red blood cell counts and hemoglobin content. The serum albumin/globulin ratio was significantly decreased. There were significant increases in serum and liver total protein, serum bilirubin, globulin, and iron levels. Data indicate that convicine produced similar alterations in blood as observed in human metabolic disease (favism).

T1150 Efficacy of Two Different Weekly Doses of Vitamin D (400 Iu and 50,000 Iu) in Patients with Crohn's Disease in Improving Vitamin D Nutritional Status

Background: Vitamin D deficiency is prevalent among patients with Crohn's disease (CD). Factors predisposing to hypovitaminosis D in these patients may include lack of adequate vitamin D intake or supplementation and malabsorption. Since these factors have been poorly described in patients with CD, the aims of this study were to assess baseline serum vitamin D status and the efficacy of a standard pharmacologic dose of vitamin D in improving serum 25(OH)D levels.Methods: Consecutive adult patients with CD presenting for routine office visits to Boston Medical Center participated in the study from April 2007 to November 2007. Baseline serum 25(OH)D levels were measured by HPLC in 21 consecutive patients after which patients were randomized to receive either 50,000 IU (n = 14) or 400 IU (n = 7) of vitamin D2 q week for seven weeks. At the end of the study, changes in serum 25(OH)D from baseline were compared. As secondary endpoints, changes from baseline in serum calcium, hematocrit, ESR, CRP were measured. In addition, changes in serum levels of 12 cytokines (GMCSF, IFN-gamma, IL-10, IL-1beta, IL-s, IL-4, IL-5, IL-6, IL-8, MCP-1, MIP-1alpha, TNF-alpha) were evaluated by using multi-analyte profiling beads (Luminex, Toronto, ON). Results: Baseline serum levels of 25(OH)D were not significantly different between treatment arms (21.3 vs. 26.1 ng/ml). Both treatment arms significantly increased serum 25(OH)D levels over baseline. Those patients receiving 50,000 IU of vitamin D weekly had a mean increase of 25(OH)D of 61% (26.1 to 37 ng/ml, p=0.007) while those receiving 400 IU of vitamin D weekly had a mean increase of 25(OH)of 128% (21.3 to 41.6 ng/ml, p=0.035). There was no significant difference in end serum levels of 25(OH)D between the treatment arms (41.6 vs. 37.8 ng/ml). Neither a significant increase in serum 25(OH)D levels nor randomization to the 50,000 IU per week arm of the study had an effect any laboratory markers of disease activity (ESR, CRP, Hct) nor on serum cytokine levels. One patient in the high dose group discontinued the study medication after 4 doses secondary to increased diarrhea. Conclusions: 50,000 IU of vitamin D given once a week for 7 weeks was no more effective than 400 IU of vitamin D given once a week for 7 weeks in raising serum 25(OH)D levels. Hence, other variables that affect serum vitamin D levels such as sun exposure due to seasonal variation over the course of the study may be responsible for the significant increase in serum 25(OH)D in each group. The lack of difference in serum 25(OH)D levels between the two groups may be due to compromised absorption secondary to their Crohn's disease.

Antioxidant and protective effects of silymarin on ischemia and reperfusion injury in the kidney tissues of rats

Renal ischemia/reperfusion (I/R) injury is a major cause of acute renal failure. Silymarin is extracted from Silybum marianum and Cynara cardunculus seeds and fruits. The aim of this study is to investigate whether silymarin administration prevents the damage induced by I/R in rat kidneys. Thirty male Wistar rats were randomly divided into five experimental groups (n = 6, each) as follows; control group, sham-operated group, I/R group, silymarin group, and I/R + silymarin group. In the I/R and I/R + silymarin groups, both renal arteries were occluded using nontraumatic microvascular clamps for 45 min. Then, at the end of 24 h of reperfusion, the animals were killed. Kidney function tests, the serum and tissue antioxidant enzymes and oxidant products were determined. Animals that were subjected to I/R exhibited significant increase in serum urea, creatinine, and cystatin C levels compared with the rats treated with silymarin prior to the I/R process (P < 0.001). The serum enzymatic activities of superoxide dismutase and glutathione peroxidase significantly decreased in the I/R group; however, this reduction was significantly improved by the treatment with silymarin (P < 0.001 and P < 0.05, respectively). Renal I/R produced a significant increase in serum and tissue malondialdehyde, nitric oxide, and protein carbonyl as compared with controls. Treatment with silymarin resulted in significant reduction in these markers (P < 0.001). Based on our findings, silymarin protects the kidneys against I/R injury. This finding may provide a basis for the development of novel therapeutic strategies for protection against the damages caused by I/R.

Activin a and follistatin in chronic heart failure

Activin A a member of TGF-B superfamily has been involved in several pathologic processes. It is also accused to have a pathognomonic role in atherogenesis and the development of heart failure. Its activity is regulated by a glycoprotein called follistatin that bind activin preventing its function. uPA is a serine protease that activates plasminogen thus initiating a cascade of fibrinolysis and extra cellular proteolysis. The aim of this study is to assess the role of activinA, follistatin and uPA in patients with chronic heart failure and to find if there is any correlation among their levels. The present study was conducted on 30 patients with chronic heart failure as a result of cardiomyopathy or ischemic heart diseases (group I). There were 20 healthy subjects of matched age and sex involved in the study as a control group (group II). In both groups serum activin A, follistatin, uPA and lipid profile that included serum T.G, total cholesterol, LDLc and HDLc were estimated. Results:there was a significant increase in serum activin A and follistatin and a significant decrease of uPA in group I as compared to controls. As regard to lipid profile there was a significant increase in serum T.G, serum total cholesterol and serum LDLc in group I than group II while there was a significant decrease in patients than the controls regarding HDLc. There was significant positive correlation between activin A and urokinase plasminogen activator (uPA) in group 1. Conclusion:activin A/follistatin system may play a role in the pathogenesis of heart failure; also uPA could be suggested to have an important role in atherosclerosis and ischemic vascular disease that predisposes to heart failure due to the possible role of activin A cytokine in the fibrinolytic activity of uPA.

STOBADINE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA/REPERFUSION INJURY

1. Ischaemia-reperfusion (I/R) injury, one of the main causes of acute renal failure, still needs satisfactory treatment for routine clinical application. Stobadine, a novel synthetic pyridoindole anti-oxidant, has the ability to reduce tissue injury induced by mechanisms involving reactive oxygen species during I/R. The aim of the present study was to determine the effects of stobadine on renal I/R injury. 2. Forty male Wistar rats were randomly divided into four groups as follows: sham, I/R, stobadine treated and I/R + stobadine treated. Stobadine (2 mg/kg, i.v.) was given intravenously to two groups of rats. The stobadine-treated group was treated with stobadine following sham operation before the abdominal wall was closed, whereas the I/R + stobadine group received stobadine at the beginning of reperfusion. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to assess: (i) serum levels of blood urea nitrogen and creatinine; (ii) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione peroxidase (GPx); (iii) renal morphology; and (iv) immunohistochemical staining for P-selectin. 3. Stobadine was able to significantly attenuate the renal dysfunction as a result of renal I/R injury. Ischaemia-reperfusion resulted in a significant increase in serum and kidney MDA levels and a decrease in serum and kidney GSH. Stobadine treatment at the beginning of reperfusion attenuated both the increased MDA levels and decreased GSH secondary to I/R injury. In addition, the decreased G-6PD activity observed after I/R was significantly attenuated by stobadine treatment. Stobadine did not alter 6-PGD activity after I/R. Neither GR nor GPx activity was significantly changed in the I/R alone or the I/R + stobadine groups compared with the sham group. In addition, stobadine decreased the morphological deterioration and high P-selectin immunoreactivity secondary to renal I/R injury. 4. A pyridoindole anti-oxidant, stobadine exerts a renal protective effect in renal I/R injury, which is probably due to its radical-scavenging and anti-oxidant activities.

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

The present study investigated the effects of Hachimi-jio-gan (HJ) on diabetic hyperglycemia in streptozotocin (STZ)-induced diabetic rats. After STZ administration, rats had free access to pellets containing 1% HJ extract powder for four weeks. HJ markedly suppressed hyperglycemia in STZ-induced diabetic rats at three and four weeks after the start of administration. There were also significant increases in serum and pancreatic immunoreactive insulin levels in STZ and HJ co-administering rats. However, in the present study, the number of beta cells in the pancreatic Langerhans' islets did not increase. Next, in order to investigate the action mechanism besides the glycemic control action of insulin, the expression of glucose transporter 2 (GLUT2) protein, which is involved in glucose uptake and release in the liver, was investigated. GLUT2 protein expression was increased by STZ administration but was normalized after four weeks of HJ administration. Therefore, irrespective of the structural changes in pancreatic beta-cells due to STZ, HJ increased insulin production and secretion by the pancreas and significantly suppressed GLUT2 synthesis in the liver. Amylase secretion from the pancreas was measured to assess pancreatic secretion. Amylase activity was decreased by STZ but was increased by HJ. Therefore, the effects of HJ on STZ-induced hyperglycemia in rats could be summarized as follows: besides increasing insulin synthesis and release, HJ normalizes GLUT2 protein expression in the liver to suppress hyperglycemia. Hence, the results of the present study suggest for the first time that HJ affects not only the production and secretion of insulin, but also the release of glucose from the liver.

BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction

Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) uses deoxyhemoglobin as an endogenous contrast agent for the noninvasive assessment of tissue oxygen bioavailability. We hypothesized that intrarenal oxygenation was impaired in patients with chronic allograft nephropathy (CAN). Ten kidney-transplant recipients with CAN and nine healthy volunteers underwent BOLD-MRI. Medullary R2* (MR2*) and cortical R2* (CR2*) levels (measures directly proportional to tissue deoxyhemoglobin levels) were determined alongside urine and serum markers of oxidative stress (OS): hydrogen peroxide (H(2)O(2)), F(2)-isoprostanes, total nitric oxide (NO), heat shock protein 27 (HSP27), and total antioxidant property (TAOP). Mean MR2* and CR2* levels were significantly decreased in CAN (increased local oxyhemoglobin concentration) compared with healthy volunteers (20.7 +/- 1.6 vs. 23.1 +/- 1.8/s, P = 0.03 and 15.9 +/- 1.9 vs. 13.6 +/- 2.3/s, P = 0.05, respectively). There was a significant increase in serum and urine levels of H(2)O(2) and serum HSP27 levels in patients with CAN. Conversely, urine NO levels and TAOP were significantly increased in healthy volunteers. Multiple linear regression analyses showed a significant association between MR2* and CR2* levels and serum/urine biomarkers of OS. BOLD-MRI demonstrated significant changes in medullary and cortical oxygen bioavailability in allografts with CAN. These correlated with serum/urine biomarkers of OS, suggesting an association between intrarenal oxygenation and OS.

Effect of ergocalciferol supplementation on serum parathyroid hormone and serum 25‐hydroxyvitamin D in chronic kidney disease

To assess the impact of the administration of ergocalciferol on serum parathyroid hormone levels at different stages of chronic kidney disease (CKD). A continuous series of 85 patients with stages 3-5 CKD but excluding patients on dialysis referred to the Kaiser Kidney Program were followed. Baseline serum intact parathyroid hormone (iPTH) and serum 25(OH)D levels were measured. All patients were administered ergocalciferol in doses ranging from 800 iu/day to 100,000 iu/week. We obtained serum levels of iPTH and 25(OH)D for a post-treatment endpoint after a median treatment period of 90 days. Pre- and post-treatment serum iPTH levels displayed a mean difference of 2.8 pmol/L (95% CI 1.3-4.4, P < 0.001). Patients with stage 4 CKD had a mean difference of 3.6 pmol/L (95% CI 1.7-5.5, P < 0.001) between pre- and post-iPTH levels. Serum iPTH levels decreased among CKD stages 3 and 5, but were not statistically significant. All CKD groups analysed in the present study had significant increases in serum 25(OH)D levels. None of the study population required cessation of vitamin D therapy and no adverse outcomes were reported. Ergocalciferol supplementation appears a safe and effective treatment for CKD populations which may raise levels of serum 25(OH)D levels and decrease iPTH levels.

The Effects of Increasing Serum Calcitriol on Energy and Fat Metabolism and Gene Expression

Evidence from a number of investigations indicates that calcium intake could be inversely related to body weight through alterations in the 1,25-OH(2)-D(3) metabolism. The objective of this study was to test whether energy and substrate metabolism and adipose tissue enzyme mRNA expression can be altered by changes in serum 1,25-OH(2)-D(3) through oral cholecalciferol supplementation in non-obese human subjects. An intervention study was used with a treatment period of 7 days. During this intervention, energy expenditure (EE) and substrate metabolism were measured using indirect calorimetry at t = 0, 1, 3, and 7 days, and blood samples were obtained at t = -1, 0, 1, 2, 3, 5 and 7 days. Fat biopsies were obtained at t = 0 and 7 days for determination of expression of genes involved in lipolytic and lipogenic pathways. Subjects from the general community were studied in an ambulatory setting at a university hospital. Ten healthy young men (age, 28 +/- 3 years; BMI, 25.5 +/- 0.5 kg/m(2)) were recruited by local announcement, and all completed the study. All subjects received 2000 IU cholecalciferol/d for 7 days, and they were instructed to consume a low-cholecalciferol, low-calcium diet. EE, fat oxidation, and adipose tissue enzyme mRNA were the main outcome measures. Despite a significant increase in serum 1,25-OH(2)-D(3) concentration at t = 5 and 7 days, no significant differences in substrate and energy metabolism nor mRNA concentrations of different lipid metabolism-related proteins were observed. Seven-day supplementation with 2000 IU cholecalciferol/d together with a decrease in dietary calcium intake does not affect EE or substrate metabolism nor gene expression of proteins related to fat metabolism, despite a significant increase in serum 1,25-OH(2)-D(3) concentration.

Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis

Objective: To study the effects of a special nutritional supplement on bone mineral density and bone turnover markers in Chilean elderly subjects with femoral osteoporosis.Setting: Public primary health care clinics in Chile.Subjects: Free living elderly subjects with femoral osteoporosis.Interventions: Subjects were randomized to receive the usual nutritional supplement provided by the Chilean Ministry of Health or a special nutritional supplement providing, among other nutrients, 90 mg isoflavones, 800 mg calcium, 400 IU vitamin D, 60 ug vitamin K and 31 g proteins per day.Measures of Outcome: At baseline, and after six and twelve months of supplementation, body composition, bone mineral density, serum 25 OH vitamin D, intact parathyroid hormone (iPTH), osteocalcin, decarboxylated osteocalcin, urinary aminoterminal telopeptide of type I collagen (NTX), deoxypyridoline cross links (Dpd) and equol were measured. Every month, urinary daidzein was measured in a morning urine sample.Results: No differences between treatment groups were observed in body composition or bone mineral density changes. The group receiving the special supplement had a significant increase in serum 25 OH vitamin D and a significant decrease in serum iPTH and decarboxylated osteocalcin. No association between daidzein or equol excretion and changes in bone mineralization was observed.Conclusions: A special supplement delivered to elderly subjects with osteoporosis improved serum vitamin D and reduced serum iPTH and undercarboxylated osteocalcin levels but did not affect BMD.

Aldosterone Antagonism in Chronic Kidney Disease

Angiotensin-converting enzyme (ACE) inhibitors are potent members of the arsenal to treat chronic kidney disease (CKD). By reducing blood pressure (BP) and disproportionately decreasing intraglomerular pressure, this class of drugs also reduces proteinuria and slows progression of CKD (1,2). Given the high prevalence of cardiovascular disease in this population, it is noteworthy that ACE inhibitors also decrease the incidence of stroke, myocardial infarction (MI), and cardiovascular mortality in patients who are at high cardiovascular risk (3). More recently, data reporting similar benefits of angiotensin receptor blockers (ARB) support their use in the treatment of CKD as well, especially in individuals with type 2 diabetes (4). Furthermore, one sizable study suggested that the combination of an ACE inhibitor and ARB may be more effective than either agent alone (5). Parving and colleagues (6) called attention to the effects of high-dose ARB therapy, up to three times the recommended dose, as an additional means of effectively interrupting the renin-angiotensin-aldosterone system (RAAS). By logical extension, further blockade of the RAAS by direct antagonism of aldosterone also may prove beneficial. Indeed, aldosterone seems to be a potent effector of renal injury (7–9). In the rare cases of primary aldosteronism and its functional analogue, the even more rare Liddle’s syndrome, the observed renal injury probably is independent of the more proximal elements of the RAAS (10,11). Animal models provide an expeditious tool for assessing pathophysiologic change and the efficacy of intervention. The classic model of primary aldosteronism, the mineralocorticoid–nephrectomy–high-salt model of hypertension, develops systemic and glomerular capillary hypertension and sustains renal damage (12). In the remnant kidney model of CKD, ACE inhibitors and ARB attenuate renal injury (13). However, this protection, which is associated with suppression of aldosterone secretion, is abrogated by exogenous aldosterone infusion with return of …

Development and Evaluation of aSarcocystis neurona‐Specific IgM Capture Enzyme‐Linked Immunosorbent Assay

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasiteSarcocystis neurona.Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged withS neuronawould have an increasedS neurona‐specific IgM (Sn‐IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on theS neuronalow molecular weight protein SNUCD‐1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 millionS neuronasporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) ofS neuronasporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn‐IgM concentrations compared with values before infection at weeks 2–6 after inoculation (P&lt; .0001). For horses inoculated with lower doses ofS neurona, there were significant increases in serum Sn‐IgM concentration at various points in time after inoculation, depending on the challenge dose (P&lt; .01). In addition, there was a significant increase between the CSF Sn‐IgM concentrations before and after inoculation (P&lt; .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

Vascular Endothelial Growth Factor And Soluble Adhesion Molecules As A Diagnostic Markers For Spontaneous Bacterial Peritonitis In Cirrhotic Liver Disease

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The aim of this study was determine serum and ascitic fluid of soluble-L selectin (s-L Selectin), intracellular adhesion molecule-1 (ICAM-1), Vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) in cirrhotic patients, and to search for a relationship between them and SBP. This study was performed on 30 cirrhotic patients with SBP. Their ages ranged (from 38- 55 years) with mean of (32 + 5.5), 30 cirrhotic patients with non-infected ascites; their ages ranged (from 30-52 years) with mean of (35 + 6.5). This group considered as cirrhotic control group and 20 healthy control subjects their ages ranged (from 28-55 years) with mean of (30 + 7.5). Serum and ascitic fluid of adhesion molecules as well as VEGF levels were significantly higher in cirrhotic patients with SBP as well as cirrhotic patients with non-infected ascites as compared to healthy control group. There were significant increase in serum and ascitic fluid level of leukocyte, PMN and ICAM-1 in SBP as compared to cirrhotic with non-infected ascites. There was non-significant decrease in serum and AF level of VEGF in cirrhotic control group as compared to SBP group. The ascitic fluid PMN and s-L Selectin were higher in culture positive SBP patients particularly in those with gram positive isolates, where these are non-significant increase in serum and ascitic fluid level of VEGF in culture positive SBP than culture negative cases. Positive correlation was found between serum and ascitic fluid level of ICAM-1 in SBP and non-infected cirrhotic group. Also, positive correlation was found between VEGF levels in serum ascetic fluid levels in both cirrhotic groups (SBP and non-infected cirrhotic group). These data suggest that: Significant elevated level of VEGF in both SBP and non infected cirrhotic patient may have pathophsiological consequences of local regulation of vascular tone and endothelial permeability, significant elevated level of adhesion molecules in both SBP and non-infected cirrhotic patients are due to inflammatory response and endothelial cell activation. Serum and ascetic fluid of ICAM-1 can be used as useful marker for diagnosis of SBP and for monitoring the treatment of cirrhotic patients.