scholarly journals New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

2004 ◽  
Vol 379 (1) ◽  
pp. 119-124 ◽  
Author(s):  
André B. P. van KUILENBURG ◽  
Alida E. M. STROOMER ◽  
Henk van LENTHE ◽  
Nico G. G. M. ABELING ◽  
Albert H. van GENNIP

DPD (dihydropyrimidine dehydrogenase) constitutes the first step of the pyrimidine degradation pathway, in which the pyrimidine bases uracil and thymine are catabolized to β-alanine and the R-enantiomer of β-AIB (β-aminoisobutyric acid) respectively. The S-enantiomer of β-AIB is predominantly derived from the catabolism of valine. It has been suggested that an altered homoeostasis of β-alanine underlies some of the clinical abnormalities encountered in patients with a DPD deficiency. In the present study, we demonstrated that only a slightly decreased concentration of β-alanine was present in the urine and plasma, whereas normal levels of β-alanine were present in the cerebrospinal fluid of patients with a DPD deficiency. Therefore the metabolism of β-alanine-containing peptides, such as carnosine, may be an important factor involved in the homoeostasis of β-alanine in patients with DPD deficiency. The mean concentration of β-AIB was approx. 2–3-fold lower in cerebrospinal fluid and urine of patients with a DPD deficiency, when compared with controls. In contrast, strongly decreased levels (10-fold) of β-AIB were present in the plasma of DPD patients. Our results demonstrate that, under pathological conditions, the catabolism of valine can result in the production of significant amounts of β-AIB. Furthermore, the observation that the R-enantiomer of β-AIB is abundantly present in the urine of DPD patients suggests that significant cross-over exists between the thymine and valine catabolic pathways.

2006 ◽  
Vol 87 (12) ◽  
pp. 3723-3727 ◽  
Author(s):  
Nicole Picard-Hagen ◽  
Véronique Gayrard ◽  
Catherine Viguié ◽  
Mohammed Moudjou ◽  
Chantal Imbs ◽  
...  

The aim of this study was to characterize the cerebrospinal fluid (CSF) prion protein (PrP) of healthy and naturally scrapie-affected sheep. The soluble form of CSF PrPC immunoblotted with an anti-octarepeat and an anti-C terminus mAb showed two isoforms of approximately 33 and 26 kDa, corresponding to the biglycosylated and unglycosylated isoforms of brain PrPC. Neither the mean concentration nor the electrophoretic profile of CSF PrP differed between healthy and scrapie-affected sheep, whereas a slightly increased resistance of CSF PrP to mild proteolysis by proteinase K was evident in the CSF of scrapie-affected sheep. No difference in susceptibility to proteolysis was observed between the two ARR and VRQ genetic variants of the purified prokaryote recombinant PrP. It was concluded that the physicochemical properties of PrPC in the CSF could be altered during scrapie and that these changes might reflect the physiopathological process of prion disease.


2007 ◽  
Vol 53 (8) ◽  
pp. 1541-1544 ◽  
Author(s):  
Hiroyuki Ebinuma ◽  
Takashi Miida ◽  
Toshimasa Yamauchi ◽  
Yusuke Hada ◽  
Kazuo Hara ◽  
...  

Abstract Background: Human serum adiponectin exists in 3 multimer forms: high molecular weight (HMW), middle molecular weight, and low molecular weight (LMW), with some of the latter bound to albumin (Alb)-LMW. Some studies have suggested that adiponectin crosses the blood–brain barrier and plays a central role in energy homeostasis. Methods: To determine cerebrospinal fluid (CSF) adiponectin at extremely low concentrations, we modified the protocol of the ELISA system used to assay serum adiponectin. The 3 multimers of adiponectin were measured separately by pretreating CSF with 2 proteases. We measured the CSF adiponectin concentrations in anonymous human samples (n = 19). The molecular sizes of adiponectin in CSF pretreated with proteases or untreated were determined by use of native PAGE and immunoblotting. Results: The ELISA system measured adiponectin in the range of 1.0–167 μg/L. The between-assay imprecision estimates (CVs) were 6%–17% for the 3 forms. The mean total CSF adiponectin concentration (7.2 μg/L) was ∼1/1000 of the mean concentration in serum. Unlike serum adiponectin, the LMW and Alb-LMW forms predominated in all of the CSF samples. Immunoblotting analysis revealed that most LMW forms were bound to Alb, although the HMW form was detected in some samples. Conclusions: The modified ELISA system measures the 3 multimers separately and is sufficiently sensitive to measure adiponectin in CSF.


Author(s):  
Y Wang ◽  
Y Zhu ◽  
W Zhang ◽  
M Liu ◽  
G Li ◽  
...  

Background: IL-27 acts as a ‘master regulator’ in modulating inflammation and was responsible for a number of autoimmune diseases. However, the role of IL-27 was not addressed in Guillain-Barré syndrome (GBS). Methods: Sixty-five subjects including 19 with GBS, 7 with encephalitis or meningitis, 23 with multiple sclerosis or neuromyelitis optica as well as 11 with other non-inflammatory neurological disorders were enrolled. ELISA was used to detect the concentrations of IL-27 in paired samples of cerebrospinal fluid and plasma. Results: The mean concentration of IL-27 in GBS patients was significantly lower than in other neurological disorders both in CSF and in plasma (all p<0.05). GBS patients with cranial involvement, decreased reflexes, hypaesthesia, autonomic nerve dysfunction, MRC score <30 are inclined to have a lower CSF IL-27 level than patients without these symptoms (182 pg/ml, 181 pg/ml, 185 pg/ml, 185 pg/ml, 194 pg/ml vs 211 pg/ml, 205 pg/ml, 202 pg/ml, 198 pg/ml, 199 pg/ml, respectively). Similar results were noted in plasma except for cranial involvement. Conclusions: Production of IL-27 was disparate between GBS and other neurological diseases and a significantly lower level of IL-27 was observed in GBS patients, indicative of an anti-inflammatory role of IL-27 in GBS.


1983 ◽  
Vol 22 (05) ◽  
pp. 246-250 ◽  
Author(s):  
M. Al-Hilli ◽  
H. M. A. Karim ◽  
M. H. S. Al-Hissoni ◽  
M. N. Jassim ◽  
N. H. Agha

Gelchromatography column scanning has been used to study the fractions of reduced hydrolyzed 99mTc, 99mTc-pertechnetate and 99mTc-chelate in a 99mTc-glucoheptonate (GH) preparation. A stable high labelling yield of 99mTc-GH complex in the radiopharmaceutical has been obtained with a concentration of 40-50 mg of glucoheptonic acid-calcium salt and not less than 0.45 mg of SnCl2 2 H2O at an optimal pH between 6.5 and 7.0. The stability of the complex has been found significantly affected when sodium hydroxide solution was used for the pH adjustment. However, an alternative procedure for final pH adjustment of the preparation has been investigated providing a stable complex for the usual period of time prior to the injection. The organ distribution and the blood clearance data of 99mTc-GH in rabbits were relatively similar to those reported earlier. The mean concentration of the radiopharmaceutical in both kidneys has been studied in normal subjects for one hour with a scintillation camera and the results were satisfactory.


1967 ◽  
Vol 55 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Benno Runnebaum ◽  
Josef Zander

ABSTRACT Progesterone was determined and identified in human peripheral blood during the preovulatory period of the menstrual cycle, by combined isotope derivative and recrystallization analysis. The mean concentration of progesterone in 1.095 ml of plasma obtained 9 days before ovulation was 0.084 μg/100 ml. However, the mean concentration of progesterone in 1.122 ml of plasma obtained 4 days before ovulation was 0.279 μg/100 ml. These data demonstrate a source of progesterone secretion other than the corpus luteum. The higher plasma-progesterone concentration 4 days before ovulation may indicate progesterone secretion of the ripening Graafian follicle of the ovary.


1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1382
Author(s):  
Olga Martyna Koper-Lenkiewicz ◽  
Violetta Dymicka-Piekarska ◽  
Anna Justyna Milewska ◽  
Justyna Zińczuk ◽  
Joanna Kamińska

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.


1979 ◽  
Author(s):  
F. Panicucci ◽  
A. Sacripanti ◽  
E. Pinori ◽  
M. Vispi ◽  
B. Conte ◽  
...  

Determinations of AT-III activity, heparin cofactor activity, antifactor Xa activity and AT-III protein were carried out in 200 healthy adults, evenly distributed within age and sex groups, in 60 patients with cerebral thrombosis and in 20 oral contraceptive users. There was a positive correlation between AT-III protein and its activitiesin normal subjects and in patients with cerebral thrombosis. In oral contraceptive users the positive correlation was between AT-III protein and its activities, antifactor Xa activity excepted. The mean AT-III protein and heparin cofactor activity values decreased in males with age and were significantly lower in the groups between 50 and 70 years. The mean AT-III protein and heparin cofactor activity values decreased slightly in women in fertile age and were lower in the 40 to 50 age-group. The mean AT-III protein and its activities values did not show any variation in the patients with cerebral thrombosis. The mean antifactor Xa activity value in the women, taking the pill for 3 months, decreased, whereas the other AT-III activities and AT-III protein were unchanged.


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