| 31. |
- Jonsson, Thomas Björn, 1971-, et al.
(författare)
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Cloxacillin concentrations in serum, subcutaneous fat, and muscle in patients with chronic critical limb ischemia
- 2014
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Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 70:8, s. 957-963
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics.This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poorly vascularized tissues, i.e., the calf and foot of patients suffering from CLI.Cloxacillin concentrations were measured by HPLC in serum and in microdialysis samples from skin and muscle of the lower part of the calf and as reference subcutaneously at the pectoral level in eight patients suffering from CLI (four males, four females, mean age 78 years, range 66-85 years) and in three healthy controls (two females, one male, mean age 67, range 66-68 years).In patients suffering from CLI, the tissue penetration of cloxacillin after a single 4 g dose was comparable to that of healthy controls, despite impaired blood circulation.The reduced blood flow in the peripheral vessels of the CLI patients presented here apparently is not the rate-limiting factor for delivery or tissue penetration of cloxacillin.
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| 32. |
- Lakso, Hans-Ake, et al.
(författare)
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Quantification of methylmalonic acid in human plasma with hydrophilic interaction liquid chromatography separation and mass spectrometric detection
- 2008
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Ingår i: Clinical Chemistry. - Washington, DC : American Association for Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 54:12, s. 2028-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measurement of methylmalonic acid (MMA) in serum or plasma is useful for diagnosing cobalamin deficiency. We developed a method for quantifying MMA in plasma based on hydrophilic interaction liquid chromatography (HILIC) and single-stage negative electrospray ionization (ESI) mass spectrometry. Methods: We deproteinized plasma samples (200 microL) with 800 microL acidified acetonitrile containing 0.17 micromol/L deuterated MMA (D(3)-MMA) internal standard, centrifuged the samples, and injected 4 microL of the supernatant into the LC-MS instrument. Separation was achieved within 3 min on a Merck SeQuant ZIC-HILIC column with a mobile phase consisting of 4 volumes acetonitrile plus 1 volume 100 mmol/L ammonium acetate buffer, pH 4.5, at a flow rate of 400 microL/min. Subsequent column washing and reconditioning contributed to a total run time of 10 min. MMA and D(3)-MMA were quantified by single-ion monitoring (m/z 117.2 and 120.2, respectively) in negative ESI mode at a drying-gas flow rate of 10 L/min, 300 degrees C, and a capillary voltage of 3.0 kV. Results: The estimated limits of MMA quantification and detection were 0.09 micromol/L and 0.03 micromol/L, respectively, in plasma. The assay was linear to 200 micromol/L. Interassay and intraassay CVs were < or = 5% at all tested concentrations. Recoveries were 90%-93%. Conclusions: This robust assay allows analysis of MMA in human plasma without derivatization. Sample preparation is simple and suitable for automation.
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| 33. |
- Manger, Mari S., et al.
(författare)
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Cobalamin Status Modifies the Effect of Zinc Supplementation on the Incidence of Prolonged Diarrhea in 6-to 30-Month-Old North Indian Children
- 2011
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 141:6, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged (>= 7 d duration) and acute diarrhea. Children aged 6-30 mo received zinc or placebo daily for 4 mo. We measured plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables. The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile. The OR (95% Cl) for children below and above the 25th percentile for cobalamin were 0.53 (0.35-0.78) and 0.90 (0.73-1.11), respectively (P-interaction = 0.015). There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA (P-interaction = 0.045 and 0.188, respectively). Baseline folate status did not modify the effect of zinc on prolonged diarrhea. Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea. Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea J. Nutr. 141: 1108-1113, 2011.
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| 34. |
- Manger, Mari S., et al.
(författare)
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Poor Folate Status Predicts Persistent Diarrhea in 6-to 30-Month-Old North Indian Children
- 2011
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Ingår i: Journal of Nutrition. - Bethesda : American Society for Nutrition. - 0022-3166 .- 1541-6100. ; 141:12, s. 2226-2232
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Tidskriftsartikel (refereegranskat)abstract
- Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India. Plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid were determined at baseline. Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial. Diarrhea episodes lasting <7, >= 7, and >= 14 d were classified as acute, prolonged, and persistent, respectively. There was a total of 4596 child periods with acute, 633 with prolonged, and 117 with persistent diarrhea during follow-up. Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [adjusted OR = 1.77(95% CI = 1.14, 2.75); P = 0.01]. This effect differed between boys [adjusted OR = 2.51 (95% CI = 1.47, 4.28)] and girls [adjusted OR = 1.03 (95% CI = 0.53, 2.01); P-interaction = 0.030]. We found a small but significant association between high plasma tHcy concentration and acute diarrhea [adjusted OR = 1.14 (95% CI = 1.04, 1.24); P = 0.006]. Plasma cobalamin concentration was not a predictor of diarrheal morbidity. In conclusion, poor folate status was an independent predictor of persistent diarrhea in this population. J. Nutr. 141: 2226-2232, 2011.
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| 35. |
- Mansoor, M Azam, et al.
(författare)
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Early biochemical and hematological response to intramuscular cyanocobalamin therapy in vitamin B-12-deficient patients
- 2013
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger AG. - 0250-6807 .- 1421-9697. ; 62:4, s. 347-353
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on early biochemical and hematological responses to cobalamin therapy in vitamin B-12-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B-12-deficient patients.Subjects and Methods: Seven female patients (mean age: 69.4 years, range: 61-78) with a mean serum cobalamin level of 104 +/- 38 pmol/l mean +/- SD and 7 male patients (mean age: 67.0 years, range: 53-78) with a mean serum cobalamin level of 84 +/- 40 (+/- SD) participated in the study. They were administered 1 mg i.m. cyanocobalamin per week for 3 weeks. Blood samples were collected before and 1, 3, 7, 14 and 21 days after cobalamin injection. The concentrations of plasma aminothiols and serum methylmalonic acid (MMA) were measured with high-performance liquid chromatography and gas chromatography/mass spectrometry, respectively, and hematological parameters were determined with a hematological analyzer.Results: Already 1 day after intramuscular Cobalamin injections, the concentrations of serum vitamin B-12 and plasma total cysteine were significantly increased while the concentrations of serum folate, plasma total homocysteine and serum MMA were decreased. Mean cell volume was also significantly decreased first after 14 days of therapy.Conclusion: Intramuscular cobalamin administration causes swift and significant changes in plasma aminothiols, whereas the first change in hematological parameters was detected only after 14 days. Copyright (C) 2013 S. Karger AG, Basel
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| 36. |
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| 37. |
- Midttun, Öivind, et al.
(författare)
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Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study
- 2007
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American society for nutrition. - 0002-9165 .- 1938-3207. ; 86:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin B-6 exists in different forms; one of those forms, pyridoxal 5'-phosphate (PLP), serves a cofactor in many enzyme reactions, including the transsulfuration pathway, in which homocysteine is converted to cystathionine and then to cysteine. Data on the relations between indexes of vitamin B-6 status and transsulfuration metabolites in plasma are sparse and conflicting.Objective: We investigated the distribution and associations of various vitamin B-6 species in plasma and their relation to plasma concentrations of transsulfuration metabolites.Design: Nonfasting blood samples from 10 601 healthy subjects with a mean age of 56.4 y were analyzed for all known vitamin B-6 vitamers, folate, cobalamin, riboflavin, total homocysteine, cystathionine, total cysteine, methionine, and creatinine. All subjects were genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C -> T polymorphism.Results: Plasma concentrations of the main vitamin B-6 vitamers-PLP, pyridoxal, and 4-pyridoxic acid-were strongly correlated. Among the vitamin B-6 vitamers, PLP showed the strongest and most consistent inverse relation to total homocysteine and cystathionine, but the dose response was different for the 2 metabolites. The PLP-total homocysteine relation was significant only in the lowest quartile of the vitamin B-6 distribution and was strongest in subjects with the MTHFR 677TT genotype, whereas cystathionine showed a graded response throughout the range of vitamin B-6 vitamer concentrations, and the effect was not modified by the MTHFR 677C -> T genotype.Conclusion: This large population-based study provided precise estimates of the relation between plasma concentrations of vitamin B-6 forms and transsulfuration metabolites as modified by the MTHFR 677C -> T genotype.
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| 38. |
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| 39. |
- Murphy, Michelle M, et al.
(författare)
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Longitudinal study of the effect of pregnancy on maternal and fetal cobalamin status in healthy women and their offspring.
- 2007
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Ingår i: Journal of Nutrition. - 0022-3166 .- 1541-6100. ; 137:8, s. 1863-1867
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Tidskriftsartikel (refereegranskat)abstract
- Compromised cobalamin status during pregnancy may put both mother and child at risk of deficiency during lactation and subsequent development. We investigated whether changes in cobalamin status during pregnancy are associated with impaired status in the mother and the cord. Plasma cobalamin, methylmalonic acid (MMA), and holotranscobalamin (holoTC) concentrations were determined in 92 women at preconception, 8, 20, and 32 wk of pregnancy, at labor, and in the cord. All variables [geometric mean percentiles 10, 90 (P(10), P(90))] were significantly reduced from preconception [cobalamin: 293 (155, 535) pmol/L; holoTC: 63 (38,98) pmol/L; MMA: 0.12 (0.09, 0.17) micromol/L] by 20 wk of pregnancy [cobalamin: 230 (123, 432) pmol/L; holoTC: 48 (34,78) pmol/L; MMA: 0.11 (0.08, 0.15) micromol/L P < 0.001]. Plasma cobalamin and holoTC remained lower throughout the remainder of pregnancy [32 wk: 198 (107, 339); labor: 224 (117, 444); P < 0.001] and [32 wk: 45 (26,82); labor: 40 (23,79); P < 0.05], respectively. By 32 wk, MMA was greater than preconception [0.14 (0.09, 0.20) micromol/L; P < 0.01]. Plasma holoTC at 32 wk and at labor was negatively correlated with cord MMA (r = -0.51, P < 0.001 and r = -0.40, P < 0.01, respectively). Women with lower holoTC at preconception had greater increases in MMA at 32 wk and at labor. Maternal MMA at 32 wk and at labor was significantly and independently associated with cord MMA only in women with lower holoTC at preconception (regression models: R(2) = 0.707, 0.682, respectively; P < 0.01). The moderate increases observed in the cobalamin biomarker, MMA, during pregnancy may indicate a functional depletion in intracellular cobalamin status.
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| 40. |
- Myte, Robin, et al.
(författare)
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Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk
- 2016
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 27:6, s. 787-796
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83.
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