Biomedical subjects

L Thorell

Publications and source records attributed to L Thorell.

7 recordsLinked to original sources

PubMed2004

The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease?

BACKGROUND: Gluten contamination in gluten-free products cannot totally be avoided. The safe threshold for gluten remains obscure. AIM: The purpose was to estimate a reasonable limit for residual gluten, based on current literature and measurement of gluten in gluten-free products on the market. METHODS: The gluten content of 59 naturally gluten-free and 24 wheat starch-based gluten-free products were analysed by enzyme-linked immunosorbent assay. The daily intake of flours was calculated in 76 adults on gluten-free diet, and the intake compared with mucosal histology. RESULTS: A number of both naturally gluten-free (13 of 59) and wheat starch-based gluten-free (11 of 24) products contained gluten from 20 to 200 ppm (=mg/kg). The median daily flour consumption was 80 g (range: 10-300). Within these limits, the long-term mucosal recovery was good. CONCLUSIONS: The threshold for gluten-contamination can safely be set at 100 ppm. Provided that the daily flour intake is even 300 g, a level of 100 ppm results in 30 mg of gluten intake. This has been shown to be safe, when correlated to histology, in clinical and challenge studies. The level can be achieved by the industry, and does not make the diet too cumbersome.

Adult↗

PubMed1999

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children.

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.

Chromatography, High Pressure Liquid↗

PubMed1996

Nucleotides in human milk: sources and metabolism by the newborn infant.

Ribonucleotides in human milk have been claimed to have several effects in recipient infants. It is, however, not known whether the nucleotides found in human milk result from degradation of nucleic acids or are actively secreted as a response to a nutritional demand of the infant. Furthermore, little is known of the newborn infant's endogenous capacity to digest nucleic acids to absorbable products. We therefore analyzed human milk, during established lactation, with respect to the concentration of nucleic acid and ribonucleotide metabolites. Expressed as nucleotide equivalents, 68 +/- 55 mumol/L were present as nucleic acid, 84 +/- 25 mumol/L as nucleotides, and 10 +/- 2 mumol/L as nucleosides. The nucleotide/nucleoside profile showed a substantial predominance for pyrimidines and uric acid. This specific profile could, at least to some extent, result from limited catalysis during storage of the milk in the breast, because enzymes capable of degrading nucleotides were found in the milk. To evaluate the endogenous capability of newborn infants to metabolize RNA and nucleotides, fetal small intestine was analyzed for relevant digestive enzymes. Such intestine, from a fetus of 22-wk gestation, digested RNA to cytidine, uridine, and uric acid in vitro. Furthermore, a fetal small intestinal homogenate generated a net increase in pyrimidines and purines when incubated with human milk, whereas when incubated with infant formula, devoid of nucleic acids, it did not.

Animals↗

PubMed1984

Association between bleeding time and platelet adherence to artery subendothelium.

The efficacy of five different factor VIII-von Willebrand factor (FVIII-VWF) preparations in mediating adherence of blood platelets to damaged vessel walls was tested in an annular perfusion chamber utilizing human arteries and reconstituted blood. FVIII-VWF-purified by Sepharose CL-4B chromatography and von Willebrand factor prepared from this preparation by dissociation with 0.25 M CaCl2 followed by Sepharose CL-6B chromatography were equally effective in mediating platelet adherence as FVIII-VWF in cryoprecipitate and in plasma from normal subjects. A commercial concentrate of FVIII-VWF (Hemofil, Hyland) used for the treatment of haemophiliacs did not mediate platelet adherence at normal levels of FVIII-VWF related properties. A recently developed high-purity FVIII-VWF preparation (Concentrate II) containing multimers of high molecular weight normalized the platelet adherence. Platelet adherence in plasma obtained from two patients with von Willebrand's disease (VWD) was impaired, but plasma samples obtained following treatment with Concentrate II mediated normal platelet adherence. The normalization of platelet adherence paralleled the normalization of the bleeding time. This platelet adherence assay offers an inexpensive and efficient in vitro tool to test the efficacy of FVIII-VWF preparations designed for VWD patients. Preparations such as cryoprecipitate and Concentrate II mediated the platelet adherence and normalized the bleeding time. The commercial preparation did not mediate platelet adherence and had no effect on the bleeding time.

Antigens↗

PubMed1984

Structure-function relationships of human factor VIII complex studied by thioredoxin dependent disulfide reduction.

A highly purified, multimeric factor VIII complex composed of VIII: vWF and some factor VIII: C contained about 100 disulfides per subunit of Mr 260,000. Limited reduction of disulfide bonds in this complex by NADPH, thioredoxin reductase and thioredoxin leads to partial disaggregation of the multimeric VIII:vWF with concomitant loss of its platelet agglutinating activity in the presence of ristocetin, and with dissociation of factor VIII:C from the complex. During this event, no Mr 260,000 subunit of VIII:vWF is discernible. However, prolonged reduction results in the appearance of different multimers, and of some Mr 260,000 subunits. An N-terminal amino acid sequence for VIII:vWF was deduced. Two half-cystine residues in this sequence were shown to be involved in the reaction with thioredoxin. It appears possible that the thioredoxin system or other redox systems may play a role in regulation of factor VIII activities and of hemostatic processes in vivo.

Amino Acid Sequence↗

PubMed1984

Purification of the factor VIII complex.

Two high purity factor VIII concentrates, type I and type II were developed for clinical trials in patients with hemophilia A and von Willebrand's disease. Fresh frozen plasma containing 1% polyethylene glycol 4000 was thawed to form cryoprecipitate, which was subsequently dissolved in citrate buffer. By addition of glycine buffer to a final concentration of 2.0 M at 26 degrees C, the bulk of fibrinogen was precipitated while factor VIII remained in solution. Factor VIII was precipitated from the glycine supernatant by addition of solid sodium chloride. The recovery of factor VIII procoagulant activity (VIII:C) per kg plasma was 271 +/- 23 units (n = 4) and 386 +/- 47 units (n = 7) for the type I and the type II preparations, respectively, while the recovery of von Willebrand factor related activity (ristocetin cofactor, VIIIR:RC) was 518 +/- 75 units and 718 +/- 90 units per kg plasma, respectively. The specific activity (units per mg protein) of VIII:C in the type I and type II preparations were 2.53 +/- 1.02 and 7.56 +/- 1.33, respectively. The specific activity (units per mg protein) of VIIIR:RC for the type I and type II preparations were 4.86 +/- 2.32 and 13.6 +/- 3.7, respectively. VIIIR:Ag was present as multimers in both preparations, and the multimeric pattern was similar to that of normal plasma. The preparations have the ability to correct the prolonged bleeding time in severe von Willebrand's disease. The factor VIII complex in the type II preparations was further purified by gel filtration on Sephacryl S-1000. This preparation was free of fibrinogen and fibronectin. Its specific activity in terms of VIII:C was 47 u/mg protein and 104 u/mg protein in terms of VIIIR:RC. The subunit of reduced factor VIIIR:Ag had Mr of 210 Kd on sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Antigens↗

PubMed1983

An in vivo study of a new factor VIII high purity preparation.

The efficacy of high purity preparations of factor VIII complex are usually lacking effect on the bleeding time in von Willebrand's disease. In this report we have studied the efficacy of a new high purity factor VIII preparation in two von Willebrand and two hemophilia A patients. The prolonged bleeding time in the patients with von Willebrand's disease was corrected after infusion of the preparation and a secondary rise in factor VIII procoagulant activity (VIII:C) demonstrated. The biological half-life time of VIII:C, in the two hemophilia A patients, was about 15 hrs. The investigation shows that this particular preparation is capable of correcting the prolonged bleeding time in von Willebrand's disease.

Adult↗