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- Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women. [JOURNAL ARTICLE]
- BMC Med 2014 Nov 26; 12(1):229.
BackgroundIron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 ¿g/L).MethodsSingle blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ¿90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and ¿ 1-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (¿ +-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.ResultsIndividually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 ¿mol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.ConclusionsErythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.Trial registration NCT01308112 (2 March 2011).
- Association Between Serum Total Bilirubin and Serum Creatinine and the Effect of Hypertension. [LETTER]
- J Clin Hypertens (Greenwich) 2014 Nov 27.
- [Age-related changes in antioxidant parameters in healthy calves between the first day of life and the 18th month taking into consideration selected metabolic parameters.] [JOURNAL ARTICLE]
- Tierarztl Prax Ausg G Grosstiere Nutztiere 2014 Nov 27; 43(1)
Objective: To follow the age-dependent development of anti-oxidative metabolic parameters in healthy cattle from birth until 18 months of age. Material and methods: Blood samples from healthy female cattle were collected at days 1 and 7 post natum (p. n.) and during the 1st, 3rd, 6th, 9th, 12th and 18th months p. n. The antioxidant parameters superoxide dismutase (SOD), glutathione peroxidase (GPX) and Trolox equivalent antioxidative capacity (TEAC), haematocrit (Hct) and the metabolic parameters total protein, albumin, bilirubin, calcium, inorganic phosphate, iron, urea, cholesterol, β-hydroxybutyrate, alkaline phosphatase, aspartate transaminase, glutamate dehydrogenase, creatine kinase and haptoglobin were determined. Results: All three antioxidant parameters displayed a comparable time-course, with a maximum at 6 months p. n. With the exception of the 9th month p. n., significantly positive correlations were found constantly. GPX activity increased continuously from 50-80 U/ml Hct on day 1 p. n. to 100-190 U/ml Hct in the 6th month p. n. The significantly lowest activities were found on the 1st and 7th days p. n. SOD activity at the 1st (4500-5600 U/g haemoglobin [Hb]) and 7th days p. n. were significantly lower than in the 1st and 3rd months p. n. Activities at 12 and 18 months displayed significantly lower values compared to the 1st, 3rd and 6th (5000-9100 U/g Hb) months p. n. The increase in the TEAC concentration from 220-290 µmol/l on day 1 to 260-340 µmol/l in the 6th month p. n. was non-significant. Thereafter, a significant decrease in the concentrations (p > 0.05) was found. Conclusion: Parallel trends for SOD, GPX and TEAC found in this study indicate a fully functioning antioxidant defence system in the calf, which is well adjusted to and able to compensate the inevitable oxidative stress of birth, onset of respiration, haemoglobin remodelling, forestomach development and other physiological processes.
- Kidney biomarkers associated with blood lead, mercury, and cadmium in premenopausal women: a prospective cohort study. [Journal Article]
- J Toxicol Environ Health A 2015; 78(2):119-31.
Certain metals are harmful to the kidney and liver at high levels, but associations with functional biomarkers at low exposure levels among premenopausal women apparently has not been evaluated. Healthy, regularly menstruating women (n = 259) were followed for up to 2 menstrual cycles with up to 16 visits. Renal and liver biomarkers were measured in serum at each clinic visit. Cadmium (Cd), lead (Pb), and mercury (Hg) were measured in whole blood at baseline. Linear mixed models were adjusted for age, body mass index (BMI), race, average calories, alcohol intake, smoking, and cycle day. Median levels of Cd, Pb, and Hg were 0.31 μg/L, 0.88 μg/dl, and 1.1 μg/L, respectively. One-third of women had diminished glomerular filtration rate (eGFR) (<90 ml/min/1.73 m(2)). Each twofold increase in Cd was associated with a negative 4.9% change in blood urea nitrogen (BUN) and bilirubin. Each twofold rise in Pb was associated with decreased eGFR and increased creatinine. A twofold elevation in Hg was associated with higher protein and reduced alkaline phosphatase. In healthy, predominantly nonsmoking women, low levels of Cd, Pb, and Hg were associated with changes in select biomarkers of kidney and liver function.
- Ex vivo 1 H nuclear magnetic resonance spectroscopy reveals systematic alterations in cerebral metabolites as the key pathogenetic mechanism of bilirubin encephalopathy. [JOURNAL ARTICLE]
- Mol Brain 2014 Nov 26; 7(1):87.
BackgroundBilirubin encephalopathy (BE) is a severe neurologic sequelae induced by hyperbilirubinemia in newborns. However, the pathogenetic mechanisms underlying the clinical syndromes of BE remain ambiguous. Ex vivo 1H nuclear magnetic resonance (NMR) spectroscopy was used to measure changes in the concentrations of cerebral metabolites in various brain areas of newborn 9-day-old rats subjected to bilirubin to explore the related mechanisms of BE.ResultsWhen measured 0.5 hr after injection of bilirubin, levels of the amino acid neurotransmitters glutamate (Glu), glutamine (Gln), and ¿-aminobutyric acid (GABA) in hippocampus and occipital cortex significantly decreased, by contrast, levels of aspartate (Asp) considerably increased. In the cerebellum, Glu and Gln levels significantly decreased, while GABA, and Asp levels showed no significant differences. In BE 24 hr rats, all of the metabolic changes observed returned to normal in the hippocampus and occipital cortex; however, levels of Glu, Gln, GABA, and glycine significantly increased in the cerebellum.ConclusionsThese metabolic changes for the neurotransmitters are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons, in a region-specific manner. Changes in energy metabolism and the tricarboxylic acid cycle may also be involved in the pathogenesis of BE.
- Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling. [JOURNAL ARTICLE]
- Mol Biosyst 2014 Nov 26.
Epithelial ovarian cancer (EOC) is the most lethal of gynecologic malignancies due to the high rate of recurrence and poor prognosis. Predicting the prognosis in patients with EOC is clinically challenging, partly because appropriate biomarkers of recurrence have yet to be explored. In this prospective study, pre-treatment plasma samples were collected from 38 patients with stage III or IV EOC who were subsequently followed up. Ultra-performance liquid chromatography mass spectrometry was used to perform metabolic profiling, which yielded five metabolites that were potential biomarkers for EOC recurrence: l-tryptophan, kynurenine, bilirubin, LysoPC (14 : 0) and LysoPE (18 : 2). A combination of these five potential biomarkers strongly predicted recurrence, the area under the curve being 0.91. In summary, the candidate biomarkers identified in this study may both facilitate clinical prediction of EOC recurrence and prognosis and serve as potential therapeutic targets in patients with EOC.
- Comparative Salivary Proteome of Hepatitis B- and C-Infected Patients. [JOURNAL ARTICLE]
- PLoS One 2014; 9(11):e113683.
Hepatitis B and C virus (HBV and HCV) infections are an important cause of cirrhosis and hepatocellular carcinoma. The natural history has a prominent latent phase, and infected patients may remain undiagnosed; this situation may lead to the continuing spread of these infections in the community. Compelling reasons exist for using saliva as a diagnostic fluid because it meets the demands of being an inexpensive, noninvasive and easy-to-use diagnostic method. Indeed, comparative analysis of the salivary proteome using mass spectrometry is a promising new strategy for identifying biomarkers. Our goal is to apply an Orbitrap-based quantitative approach to explore the salivary proteome profile in HBV- and HCV-infected patients. In the present study, whole saliva was obtained from 20 healthy, (control) 20 HBV-infected and 20 HCV-infected subjects. Two distinct pools containing saliva from 10 subjects of each group were obtained. The samples were ultracentrifuged and fractionated, and all fractions were hydrolyzed (trypsin) and injected into an LTQ-VELOS ORBITRAP. The identification and analyses of peptides were performed using Proteome Discoverer1.3 and ScaffoldQ + v.3.3.1. From a total of 362 distinct proteins identified, 344 proteins were identified in the HBV, 326 in the HCV and 303 in the control groups. Some blood proteins, such as flavin reductase (which converts biliverdin to bilirubin), were detected only in the HCV group. The data showed a reduced presence of complement C3, ceruloplasmin, alpha(1)-acid glycoprotein and alpha(2)-acid glycoprotein in the hepatitis-infected patients. Peptides of serotransferrin and haptoglobin were less detected in the HCV group. This study provides an integrated perspective of the salivary proteome, which should be further explored in future studies targeting specific disease markers for HBV and HCV infection.
- Internal-external percutaneous transhepatic biliary drainage for patients with malignant obstructive jaundice. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(21):9391-4.
To evaluate the effect of internal-external percutaneous transhepatic biliary drainage (IEPTBD) for patients with malignant obstructive jaundice.During the period of January 2008 and July 2013, internal-external drainage was performed in 42 patients with malignant obstructive jaundice. During the procedure, if the guide wire could pass through the occlusion and into the duodenum, IEPTBD was performed. External drainage biliary catheter was placed if the occlusion was not crossed. Newly onset of infection, degree of bilirubin decrease and the survival time of patients were selected as parameters to evaluate the effect of IEPTBD.Twenty newly onset of infection were recorded after procedure and new infectious rate was 47.6%. Sixteen patients with infection (3 before, 13 after drainage) were uncontrolled after procedure, 12 of them (3 before, 9 after drainage) died within 1 month. The mean TBIL levels declined from 299.53 umol/L before drainage to 257.62 umol/L after drainage, while uninfected group decline from 274.86 umol/L to 132.34 umol/Lp (P < 0.5). The median survival time for uninfected group was 107 days, and for infection group was 43 days (P < 0.05).The IEPTBD drainage may increase the chance of biliary infection, reduce bile drainage efficiency and decrease the long-term prognosis, and the external drainage is a better choice for patients with malignant obstructive jaundice need to biliary drainage.
- Population Pharmacokinetics of Micafungin and its Metabolites M1 and M5 in Children and Adolescents: Towards Further Certainty in Dosing. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Nov 24.
The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtained from four Phase I and two Phase III clinical trials. Population pharmacokinetic models were used to simulate the proportion of children who had a steady-state area under the concentration-time curve (AUC24) of micafungin within the 10(th) to 90(th) percentile range observed in a population of adults receiving a dose of micafungin with established efficacy for invasive candidiasis (100 mg/day), i.e., 75 to 139 μg⋅h/ml. Simulated pediatric dosages of 0.5 to 5 mg/kg/day were explored. A two-compartment model was used that incorporated body weight as a predefined covariate for allometric scaling of the pharmacokinetic parameters. During construction of the model, aspartate aminotransferase and total bilirubin were also identified as covariates that had a significant effect on micafungin clearance. A dose of 2 mg/kg resulted in the highest proportion of children within the predefined micafungin AUC target range for invasive candidiasis. Cut-offs of either 40 kg or 50 kg for weight-based dosing resulted in heavier children being appropriately dosed. Thus, dose regimens of 1, 2, and 3 mg/kg/day micafungin are appropriate for prevention and treatment of invasive candidiasis, and treatment of esophageal candidiasis, respectively, in children aged 4 months to <17 years.
- Surgical rehabilitation of short and dysmotile intestine in children and adults. [JOURNAL ARTICLE]
- Scand J Gastroenterol 2014 Nov 25.:1-9.
Abstract Aims. This is a descriptive study aiming to compare outcomes of intestinal rehabilitation surgery among pediatric and adult intestinal failure (IF) patients with either primary intestinal motility disorders or short bowel syndrome (SBS) treated by our nationwide program. Methods. Medical records of IF patients (n = 31, 71% children) having undergone autologous intestinal reconstructions (AIR) (n = 25), intestinal transplantation (ITx) (n = 5), or being listed for ITx (n = 2) between 1994 and 2014 were reviewed. Results. At surgery, median age was 3.4 (interquartile range, 1.0-22.1) in SBS (n = 22) and 16.5 (3.2-26.7) years in dysmotility patients (n = 9) who received median 60% and 83% of energy requirement parenterally, respectively. Median small bowel length was shorter in SBS than dysmotility patients (34 versus 157 cm, p < 0.001). Following AIR, none of the dysmotility patients achieved permanent intestinal autonomy, whereas 68% of SBS patients weaned off parenteral nutrition (PN) (p = 0.022) and none required listing for ITx. Five dysmotility patients who underwent ITx achieved intestinal autonomy. Regarding both AIR and ITx procedures, no significant difference in PN weaning was observed between the two subgroups. At last follow-up, 3.3 (0.6-8.0) years postoperatively, median plasma bilirubin was 6 (4-16) µmol/l, while liver biopsy showed fibrosis (Metavir stage 1-2) in 50% and cholestasis in 8%. Proportion of PN energy requirement had reduced significantly (p = 0.043) among PN-dependent SBS (n = 7) but not among dysmotility patients (n = 5). Overall survival was 90%. Conclusion. AIR surgery was beneficial among selected SBS patients, whereas in intestinal dysmotility disorders, permanent PN weaning was only achieved by ITx.