Effects of intravenous magnesium sulfate on serum calcium-regulating hormones and plasma and urinary electrolytes in healthy horses.

Intravenous magnesium sulfate (MgSO4) is used in equine practice to treat hypomagnesemia, dysrhythmias, neurological disorders, and calcium dysregulation. MgSO4 is also used as a calming agent in equestrian events. Hypercalcemia affects calcium-regulating hormones, as well as plasma and urinary electrolytes; however, the effect of hypermagnesemia on these variables is unknown. The goal of this study was to investigate the effect of hypermagnesemia on blood parathyroid hormone (PTH), calcitonin (CT), ionized calcium (Ca2+), ionized magnesium (Mg2+), sodium (Na+), potassium (K+), chloride (Cl-) and their urinary fractional excretion (F) after intravenous administration of MgSO4 in healthy horses. Twelve healthy female horses of 4-18 years of age and 432-600 kg of body weight received a single intravenous dose of MgSO4 (60 mg/kg) over 5 minutes, and blood and urine samples were collected at different time points over 360 minutes. Plasma Mg2+ concentrations increased 3.7-fold over baseline values at 5 minutes and remained elevated for 120 minutes (P < 0.05), Ca2+ concentrations decreased from 30-60 minutes (P < 0.05), but Na+, K+ and Cl- concentrations did not change. Serum PTH concentrations dropped initially to rebound and remain elevated from 30 to 60 minutes, while CT concentrations increased at 5 minutes to return to baseline by 10 minutes (P < 0.05). The FMg, FCa, FNa, FK, and FCl increased, while urine osmolality decreased from 30-60 minutes compared baseline (P < 0.05). Short-term experimental hypermagnesemia alters calcium-regulating hormones (PTH, CT), reduces plasma Ca2+ concentrations, and increases the urinary excretion of Mg2+, Ca2+, K+, Na+ and Cl- in healthy horses. This information has clinical implications for the short-term effects of hypermagnesemia on calcium-regulation, electrolytes, and neuromuscular activity, in particular with increasing use of Mg salts to treat horses with various acute and chronic conditions as well as a calming agent in equestrian events.

Mechanisms of Enhanced Osteoclastogenesis in Alkaptonuria.

Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients, bone involvement represents an important clinical issue, which we investigated. Serum levels of receptor activator of NF-κB ligand (RANKL), osteoprotegerin, sclerostin, Dickkopf-1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD. In the two AKU children, the average of LS-BMD and femoral-BMD Z-scores were within the normal range, but reduced with respect to the controls. Otherwise, in the adult AKU patients, LS-BMD T-score was inside the normal range, but femoral-BMD T-score reached osteopenic levels. Consistently, in AKU adults, higher RANKL and C-terminal telopeptide of collagen type 1 and lower osteoprotegerin levels were observed than in controls. Otherwise, spontaneous osteoclastogenesis was already evident in peripheral blood mononuclear cell cultures from AKU children, together with a high percentage of circulating osteoclast precursors. Osteoclastogenesis was sustained by the high levels of tumor necrosis factor-α, RANK, RANKL, and LIGHT. In conclusion, the altered osteoclastogenesis was observed already in AKU children, despite the absence of evident injury. Thus, a preventive approach in young patients, targeting osteoclast activity, may prevent the macroscopic bone disease that appears in adult AKU.

Detection of PCT and urinary ß2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection.

OBJECTIVE: The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary ß2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. METHODS: A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary ß2 -MG in both UUTI and LUTI patients were measured and compared. RESULTS: The level of PCT and ß2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary ß2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. CONCLUSIONS: Both PCT and ß2 -MG could be used to localize the UTI. Introducing urinary ß2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice.

Serum procalcitonin levels in combination with (1)H NMR spectroscopy: A rapid indicator for differentiation of urosepsis.

BACKGROUND: Urosepsis, a severe form of sepsis requires immediate medical attention for prognosis. It is clinically diagnosed by estimating serum procalcitonin (PCT) levels along with time taking urine and blood cultures. We explored NMR based profiling, deriving metabolites that could potentially aid diagnosis. METHODS: The proton NMR of serum and urine samples of healthy control subjects (n=32) and urosepsis cases (n=35) based on PCT levels, were analyzed. Four clinically identified non-urosepsis cases with high PCT levels were also differentiated through principal component analysis (PCA) of the serum samples. RESULTS: Quantification of serum and urine through Discriminant Function Analysis (DFA) afforded 93.7% and 91.7% correct classification respectively, along with identification of malonate and urea as potential biomarkers for the disease in both urine and serum samples. The partial least square discriminant analysis (PLS-DA) showed an R(2) value of 0.97 in both biofluids with Q(2)=0.87 and 0.85 for serum and urine respectively. The training set of serum samples provided precise prediction of the test set in a small cohort through random re-sampling method, while in urine samples, the predictions were inconclusive. CONCLUSIONS: Our pilot study reveals that (1)H NMR of serum metabolic profiling in combination with PCT levels may provide a rapid method for differentiation of urosepsis.

Lab-score is a valuable predictor of serious bacterial infection in infants admitted to hospital.

Parents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7% and specificity of 98.6% in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75% and specificity of 97.7%. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.

Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis.

BACKGROUND: The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. METHODS: We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionitis. RESULTS: PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. CONCLUSIONS: In women with subclinical IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.

[Comparison of two protocols of febrile urinary tract infection management in children]. / Comparaison de deux protocoles de prise en charge des infections urinaires fébriles de l'enfant.

PURPOSE: To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost. METHODS: This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts. RESULTS: A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (€2235 in 2005, €2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (€1292 versus €1882 in 2005; P=0.0042). CONCLUSION: Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.

Contribution of procalcitonin to occult bacteraemia detection in children.

We conducted a prospective study in 215 children, 3 to 36 months of age, presenting with fever > or = 39 degrees C without obvious origin, in order to evaluate the diagnostic value of procalcitonin (PCT) in detection of occult bacteraemia. PCT associated with white blood cell count constitutes an efficient screening method with sensitivity 100%, specificity 61.9% and positive and negative likelihoods ratios of 2.62 and 0, respectively.

Sensitive capillary chromatography mass spectrometric methods for the determination of salcatonin in human biological matrices.

New methods employing capillary liquid chromatography in combination with time-of-flight mass spectrometry (microLC-TOF/MS) were developed for the rapid determination of salcatonin in human urine and plasma. The present approaches utilize (13)C(6)-leucine (19)-labeled salcatonin as internal standard, small matrix volumes and simple sample preparation procedures. They allow TOF/MS to be used as a highly selective detector for providing accurate quantitation of salcatonin. Data acquisition was performed in enhanced mode optimizing the signal for the triply charged species of salcatonin and its internal standard. We demonstrate that the determination of salcatonin is straightforward and reliable and can be performed with excellent linearity (R(2)>0.999), precision and accuracy over the concentration ranges of 2.9-290 pmol/mL in human urine, and 7.3-730 pmol/mL in human plasma.

Discovery of a dihydropyrimidine series of molecules that selectively mimic the biological actions of calcitonin.

The use of a multiplex mimetic assay led us to identify 1,4-dihydropyrimidines with potent and selective calcitonin receptor mimetic activity. Subsequent modification of the dihydropyrimidine scaffold led to a series of molecules that were efficacious in a neonatal mouse calvaria in vitro model. Dihydropyrimidine 5h, in particular, was identified as a calcitonin mimetic (EC(50)=6 microM), active in-vivo in the Weanling rat model when administered subcutaneously.

Cytokines and chemokines in serum and urine as early predictors to identify septic patients on intensive care unit.

The aim of this prospective cohort study was to address the feasibility of measuring cytokines in serum and urine as early predictor tests for the identification of septic Intensive Care Unit (ICU) patients. The study group consisted of 10 septic and 5 non-septic patients at the onset of sepsis according to modified definitions by the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Serum and urine samples were taken from septic patients at the onset of sepsis and from non-septic patients, every 12 h for 3 days and thereafter every 24 h until day 10. Levels of TNF-alpha, IL-1beta, IL-6, IL-10, IL-18, IFN-gamma, MCP-1, and PCT (procalcitonin) were measured by ELISA. Apart from serum IL-18 and PCT levels, which were elevated in septic patients (p<0.05), levels of all other cytokines and chemokines in the serum of septic patients did not exceed those of the control group. In urine, in contrast with TNF-alpha, IL-1beta, IL-6, IL-10, IFN-gamma, and MCP-1 in which no differences between the two groups were observed, a distinct trend of elevated IL-18 levels was observed only in the septic group. Whereas elevated serum IL-18 and PCT are clear candidate markers for sepsis criteria, the present data indicating elevated urine IL-18 levels albeit from a limited number of septic patients is an interesting observation. The profile of inflammatory mediators in serum and urine from septic patients herein warrants further investigations in a larger group of patients at the onset of sepsis driven by different infectious foci.

The plasma elimination rate and urinary secretion of procalcitonin in patients with normal and impaired renal function.

BACKGROUND AND OBJECTIVE: The amount of procalcitonin eliminated in the urine and the plasma disappearance rate of procalcitonin were evaluated in patients with normal and impaired renal function, because patients with sepsis are a main target group for procalcitonin measurement, and these patients often develop renal dysfunction. METHODS: Elimination of procalcitonin in the urine (microgram 12 h-1) was measured in 76 patients. In another 67 patients, the 50% plasma disappearance rate (t1/2, h) was evaluated 48 h after peak concentrations (procalcitonin > 2 micrograms L-1). Renal function was assessed by creatinine clearance. RESULTS: Procalcitonin elimination in the urine was significantly reduced in patients with severe renal dysfunction. However, the plasma disappearance rate correlated only weakly with renal dysfunction (Spearman's rank correlation R = -0.36, P = 0.004, regression t1/2 = 49.87-0.15 creatinine clearance). The 25% quartile and median were 25.2 h and 30.0 h in patients with normal renal function, and 36.3 h and 44.7 h in patients with severely impaired renal function (creatinine clearance < 30 mL min-1). CONCLUSIONS: Renal elimination of procalcitonin is not a major mechanism for procalcitonin removal from the plasma. Although the plasma disappearance rate may be prolonged up to 30-50% in some patients with renal dysfunction, clinical diagnostic decisions may not be severely influenced by this moderate prolongation of procalcitonin elimination. We conclude that procalcitonin can be used diagnostically in patients with renal failure as well as in those with normal renal function.

[Urinary tract infection and biological markers: C-reactive protein, interleukins and procalcitonin]. / Infection urinaire et marqueurs biologiques: protéine C réactive, interleukines et procalcitonine.

Serum C reactive protein (CRP) remains a good marker of the severity of urinary tract infections in children, despite false negative results. Serum IL-6 is not a better marker; urinary IL-6 might have a better prognostic value as it is higher in patients with renal lesions due to infection, but low values are found in some cases. Serum procalcitonin levels are correlated with the importance of renal scars at scintigraphy, with less than 10% of false negative results. Further studies are needed to confirm the sensitivity and sensibility of these markers, especially for procalcitonin.

Increased basal concentrations of plasma endothelin in borderline hypertension.

BACKGROUND: There is evidence for an altered endothelial function in established hypertension but little is known about endothelial function in borderline hypertension. It has also been suggested that the early stages of hypertension are characterized by an increased sympathetic drive. OBJECTIVE: To investigate whether alterations in endothelin, neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are already present in the borderline hypertensive stage. DESIGN: A case-control study of age-matched men recruited from a population screening programme. METHODS: Seventy-five men with stable borderline hypertension [diastolic blood pressure (DBP), 85-94 mmHg] and 75 age- and sex-matched normotensive controls (DBP < or = 80 mmHg) were investigated. Plasma samples were drawn in a standardized fashion, and extracted and analysed using competitive radio immunoassays. RESULTS: Basal concentrations of NPY and CGRP were similar in the two groups (28.4 versus 26.7 pmol/l and 24.2 versus 21.7 pmol/l, respectively). Basal concentrations of endothelin were significantly higher in the borderline hypertensive group (2.0 versus 1.5 pmol/l, P < 0.0001). CONCLUSIONS: These results suggest that a disturbed endothelial function, represented by endothelin, could be involved in the early hypertensive processes. They also suggest that these changes could be present before the basal sympathetic/parasympathetic drive alters, warranting further research into this area.

[The influence of hypervolemia on the secretion of atrial natriuretic peptide, the renin-angiotensin-aldosterone system's activity and concentration of vasopressin, parathormone and calcitonin in hepatitis B virus infected patients with chronic liver diseases]. / Wplyw hiperwolemii na wydzielanie przedsionkowego peptydu natriuretycznego, czynnosc ukladu renina-angiotensyna-aldosteron oraz stezenie wazopresyny, parathormonu i kalcytoniny u chorych na przewlkle choroby watroby wywolane wirusem zapalenia watroby typu B.

The influence of 1000 ml of 0.9% NaCl infusion induced hypervolemia on the water-electrolyte and hormonal balance was investigated in HBV-infected patients with chronic persistent hepatitis, chronic active hepatitis and compensated cirrhosis. All examined patients showed higher concentrations of vasopressin and atrial natriuretic peptide and the increased activity of RAA system before the trial. The induced hypervolemia caused the decrease of RAA system's activity and vasopressin concentration and increase of atrial natriuretic peptide's secretion, different in every group of patients. The latent deficiency of calcium and magnesium was found, too. The results showed that all determined patients had water-electrolyte and hormonal disorders, significantly increased in patients with chronic active hepatitis.

Biodistribution of calcitonin encapsulated in liposomes in mice with particular reference to the central nervous system.

The biodistribution of [125I]porcine calcitonin (pCT) encapsulated in reverse-phase evaporation vesicles (REVs) in mice upon the intravenous administration was examined. It was found that sulfatide significantly improved the stability of REVs in vivo, and altered the relative distribution of [125I]pCT encapsulated in liposomes in mice. These sulfatide-containing REVs were able to target [125I]pCT into the liver and central nervous system (CNS) reasonably well, with the maximal effect of about 40% and 2% of the injected doses occurring at 30 min and 90 min, respectively, after injection. Neither free [125I]pCT, nor sulfatide-free liposome-encapsulated [125I]pCT, nor a mixture of free [125I]pCT and empty sulfatide liposomes was effective. [125I]pCT was widely distributed in the CNS, with predominance in hypothalamus, brainstem, striatum and spinal cord. The results indicate that pCT encapsulated in sulfatide-containing liposomes is able to pass through the blood-brain barrier (BBB), and calcitonin, thus encapsulated, may be applicable to studies on its functions in the CNS.

Colonic absorption of human calcitonin in man.

1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study. 2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 +/- 0.7 min and 37.8 +/- 2.5 min. 3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00-0.22%. 4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects. 5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.

Hormone studies in Myxine glutinosa: failure of calcitonin to influence urine flow or plasma and urine electrolyte balance.

Hagfish, Myxine glutinosa, were used in a series of experiments to determine a possible role for calcitonin in plasma and urine electrolyte balance. Individual animals were anaesthetised and implanted with polythene cannulae for monitoring blood pressure and for infusion/injection. Urine was collected by manual palpation of the body surface whilst blood samples were withdrawn from the lateral sinus. Following injection of either 1.25 or 3.75 micrograms kg body wt-1 calcitonin, there was no significant change in either the plasma or urine composition of sodium, potassium, calcium, or magnesium ion levels. These results indicate that calcitonin may not be involved in electrolyte homeostasis in Myxine.

Age and sex influences on urine calcitonin-like immunoreactivity in normal subjects.

Calcitonin-like immunoreactivity levels were determined in urine specimens in 585 normal subjects of various ages. Urine calcitonin-like immunoreactivity (uCTi) was measured by the midportion-specific radioimmunoassay after extraction of urine by gel chromatography on a 0.8 X 20 cm column of Bio Gel P-2. In 197 males and 169 females below 20 years old, significant negative correlations between the age and uCTi were observed (male: r = -0.684, female: r = -0.690). In 75 males and 80 females above 41 years, however, no significant correlation was observed between age and uCTi. The high level of uCTi in children could be explained by high levels of circulating calcitonin, associated with rapid bone growth; however the uCTi level in the elderly may not reflect the physiological significance of calcitonin for them because of a suspected age-related decrease in renal clearance of uCTi in the elderly.