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Biomedical subjects

C Vermeer

Publications and source records attributed to C Vermeer.

At least 19 recordsLinked to original sources
PubMed2002

Menaquinone-4 in breast milk is derived from dietary phylloquinone.

The effect of maternal phylloquinone supplementation on vitamin K in breast milk was studied to establish: (1) if phylloquinone is the source of menaquinone-4 in breast milk; (2) the dose-effect relationship between intake and obtainable levels. Four groups of lactating mothers with a full-term healthy infant participated and took oral phylloquinone supplements of 0.0 (n 8), 0.8 (n 8), 2.0 (n 8), and 4.0 (n 7) mg/d for 12d, starting at day 4 post-partum. Milk samples were collected on days 4, 8, 16, and 19. Blood samples were collected on days 4 and 16. Vitamin K and vitamin E concentrations, the latter for reason of comparison, were assayed. Phylloquinone and menaquinone-4 were present in all milk samples: 5.84 (SD 2.31) and 2.98 (SD 1.51) nmol/l (n 31) respectively, in colostrum (day 4 sample). A strong correlation between the vitamers was found (r 0.78, P<0.001). Breast-milk phylloquinone levels were raised in a dose-dependent manner: 4-, 12-, and 30-fold on day 16 for the 08, 2.0, and 4.0 mg group respectively. In addition, menaquinone-4 levels were higher: 2.5- (P<0.05) and 7-fold (P<0.001) in the 2.0 and 4.0 mg groups respectively. Plasma of supplemented subjects contained 3-, 5-, and 10-fold higher phylloquinone levels on day 16. Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma samples. All day 16 plasma samples of the 4mg supplemented group contained the vitamin. There was no correlation between the K-vitamers in plasma. Vitamin E and phylloquinone appear to differ in their distribution in breast milk, milk:plasma concentration ratios were < or =1 and 3-5 for vitamin E and phylloquinone respectively. The milk:plasma concentration ratio of menaquinone-4 was >10. In conclusion, dietary phylloquinone is a source of menaquinone-4 in breast milk. Phylloquinone supplementation to lactating mothers may be of benefit to the newborn infant, since both phylloquinone and menaquinone-4 are raised by supplementation.

Antifibrinolytic Agents↗
PubMed2002

Bone mineral density in patients with classic galactosaemia.

BACKGROUND: Diminished bone mineral density (BMD) is a well known complication in women with classic galactosaemia caused by premature ovarian failure. Diminished BMD in prepubertal patients of either sex has, however, only been reported once. AIM: To assess BMD in children with classic galactosaemia. METHODS: Eleven treated patients (five males, six females, aged 2-18 years) had BMD determined by dual energy x ray absorptiometry. Two measurements were performed, an areal measurement of the total body and a volumetric measurement of the femoral neck. Results were expressed as Z scores. Dietary calcium intake, blood calcium, phosphate, vitamin D, parathormone, and markers of bone formation (bone alkaline phosphatase, osteocalcin) and bone resorption (NTX) were determined. RESULTS: All patients had a significantly diminished BMD. Mean Z score of the volumetric BMD was -1.76 (range -0.7 to -3.3), and of the areal BMD -0.99 (range -0.5 to -1.4). Dietary calcium intake and calcium, phosphate, parathormone, bone alkaline phosphatase, vitamin D metabolites, and osteocalcin (free and carboxylated) were normal in all patients. NTX levels in blood were significantly lower (p < 0.001) than in control subjects. CONCLUSION: BMD in this group of children of both sexes with classic galactosaemia under dietary treatment was decreased. Lower NTX levels in galactosaemics point to an apparent decreased bone resorption.

Absorptiometry, Photon↗
PubMed2001

Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall.

Vitamin K-dependent matrix Gla protein (MGP) has been suggested to play a role in the inhibition of soft-tissue calcification. Here we report the expression of recombinant prokaryotic MGP as part of a fusion protein and the preparation of two antibodies that specifically recognize MGP. Monoclonal antibodies were raised against synthetic peptides homologous to the sequences 3-15 and 63-75 of human MGP. Both antibodies recognize recombinant and synthetic human MGP. Immunohistochemical analysis showed that MGP was associated with the extracellular matrix of noncalcified bone and with chondrocytes in cartilage. In the healthy human arterial vessel wall, MGP antigen was demonstrated in association with smooth muscle cells and elastic laminae of the tunica media and with the extracellular matrix of the adventitia. Colocalization with the elastic laminae was lost at sites of medial calcification; in both human and rat arteries, high amounts of MGP were found in the extracellular matrix at borders of intimal and medial calcification. Our data demonstrate the close association between MGP and calcification. It is suggested that undercarboxylated MGP is biologically inactive and that poor vascular vitamin K status may form a risk factor for vascular calcification.

Animals↗
PubMed2001

Vitamin K-dependent and vitamin K-independent hypocoagulant effects of dietary fish oil in rats.

In rats, dietary fish oil causes a plasma triglyceride-lowering as well as hypocoagulant effect. The latter is apparent from reduced levels of vitamin K-dependent coagulation factors and a decreased thrombin-forming potential of the coagulating plasma. Here, we describe that intervention with low levels of n-3 polyunsaturated fatty acids (n-3 PUFAs, about 2.5% of digestible energy, en%) resulted in no more than a small reduction in coagulation factors, when supplied as part of a high-fat diet relatively rich in vitamin K. Plasma triglycerides also remained unchanged. On the other hand, when feeding rats with low- or high-fat diets restricted in vitamin K, intervention with 3 en% of n-3 PUFAs acids (fish oil) caused only a lowering in triglycerides in combination with high fat. The fish caused a reduction in coagulation potential and levels vitamin K-dependent coagulation factors (prothrombin and factor VII) that was most prominent with the low-fat diet. Fish oil, in combination with low fat but not with high fat, reduced the vitamin K levels in the liver of the animals. In addition, regardless of the fat content, the vitamin K-independent coagulation factor V was decreased in the fish oil groups. Taken together, these results indicate that, in the rat, the hypocoagulant effect of a low dose of n-3 PUFAs is most apparent at low intakes of both vitamin K and fat, is not linked to the triglyceride plasma level, but involves modulation of both vitamin K-dependent and -independent coagulation factors.

Animals↗
PubMed2001

A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels.

Matrix gamma-carboxyglutamic acid protein (MGP) is a mineral-binding extracellular matrix protein synthesized by vascular smooth muscle cells (VSMCs) and chondrocytes that is thought to be a key regulator of tissue calcification. In this study, we identified four polymorphisms in the promoter region of the human MGP gene. Transfection studies showed that the G-7A and T-138C polymorphisms have an important impact on in vitro promoter activity when transiently transfected into VSMCs. We found that one of these polymorphisms (T-138C) is significantly correlated with serum MGP levels in human subjects. Promoter deletion analysis showed that this polymorphism lies in a region of the promoter critical for transcription in VSMCs. This region contains a potential activating protein-1 (AP-1) binding element located between -142 and -136. We have demonstrated that the T-138C polymorphism results in altered binding of an AP-1 complex to this region. The -138T allelic variant binds AP-1 complexes consisting primarily of c-Jun, JunB and its partners Fra-1 and Fra-2 in rat VSMC. Furthermore, the -138T variant form of the promoter was induced following phorbol 12-myristate 13-acetate treatment, while the -138C variant was refractive to phorbol 12-myristate 13-acetate treatment, confirming that AP-1 factors preferentially bind to the -138T variant. This study therefore suggests that a common polymorphism of the MGP promoter influences binding of the AP-1 complex, which may lead to altered transcription and serum levels. This could have important implications for diseases such as atherosclerosis and aortic valve stenosis, since it strongly suggests a genetic basis for regulation of tissue calcification.

Animals↗
PubMed2001

Role of vitamin K and vitamin K-dependent proteins in vascular calcification.

OBJECTIVES: To provide a rational basis for recommended daily allowances (RDA) of dietary phylloquinone (vitamin K1) and menaquinone (vitamin K2) intake that adequately supply extrahepatic (notably vascular) tissue requirements. BACKGROUND: Vitamin K has a key function in the synthesis of at least two proteins involved in calcium and bone metabolism, namely osteocalcin and matrix Gla-protein (MGP). MGP was shown to be a strong inhibitor of vascular calcification. Present RDA values for vitamin K are based on the hepatic phylloquinone requirement for coagulation factor synthesis. Accumulating data suggest that extrahepatic tissues such as bone and vessel wall require higher dietary intakes and have a preference for menaquinone rather than for phylloquinone. METHODS: Tissue-specific vitamin K consumption under controlled intake was determined in warfarin-treated rats using the vitamin K-quinone/epoxide ratio as a measure for vitamin K consumption. Immunohistochemical analysis of human vascular material was performed using a monoclonal antibody against MGP. The same antibody was used for quantification of MGP levels in serum. RESULTS: At least some extrahepatic tissues including the arterial vessel wall have a high preference for accumulating and using menaquinone rather than phylloquinone. Both intima and media sclerosis are associated with high tissue concentrations of MGP, with the most prominent accumulation at the interface between vascular tissue and calcified material. This was consistent with increased concentrations of circulating MGP in subjects with atherosclerosis and diabetes mellitus. CONCLUSIONS: This is the first report demonstrating the association between MGP and vascular calcification. The hypothesis is put forward that undercarboxylation of MGP is a risk factor for vascular calcification and that the present RDA values are too low to ensure full carboxylation of MGP.

Arteriosclerosis↗
PubMed2001

Abnormal bone turnover in long-standing Crohn's disease in remission.

BACKGROUND: A high prevalence of osteoporosis is found in patients with Crohn's disease. The pathogenesis of this condition seems to be multifactorial and its pathophysiology is still not completely understood. AIM: To elucidate the pathophysiology of osteopenia in quiescent Crohn's disease. METHODS: Bone turnover was studied in 26 patients (13 males and 13 females) with long-standing quiescent Crohn's disease and small bowel involvement. Bone mineral density was assessed by dual energy X-ray absorptiometry. Biochemical markers for bone formation (osteocalcin and bone-specific alkaline phosphatase) and for bone resorption (deoxypyridinoline and collagen type I C-terminal crosslinks) were measured. Urinary calcium excretion was determined. RESULTS: Markers for bone formation were significantly lower in patients than in controls (osteocalcin: P= 0.027, bone-specific alkaline phosphatase: P < 0.001), but both bone resorption markers were not significantly different. Urine calcium excretion was significantly decreased in patients (P=0.002) compared to controls. Bone mineral density of the lumbar spine was significantly and inversely correlated with bone-specific alkaline phosphatase and collagen type I C-terminal crosslinks. CONCLUSIONS: Bone turnover in long-standing Crohn's disease in clinical remission is characterized by suppressed bone formation and normal bone resorption. Urine calcium excretion is decreased. Hence, interventions and therapy should be directed towards the improvement of bone formation.

Absorptiometry, Photon↗
PubMed2001

The impact of relocation on elderly patients with mental illness.

Twenty-three elderly patients with long-term mental illness were relocated from a large tertiary mental health facility to two extended care units (ECUs) in their district of origin. The patients were assessed on measures of functioning, aggression and agitation at 6 weeks pre-relocation, and again at 6 weeks and 6 months post-relocation. The impact of relocation on the group proved to be less dramatic than findings reported in the literature. The adverse affects of relocation were likely to have been offset by the preparation and planning undertaken prior to relocation, and the support provided to staff and patients in the period following relocation. The findings have implications for nursing staff involved in the relocation of people with mental illness between wards within a hospital or from one hospital to another.

Adaptation, Psychological↗
PubMed2001

Total chemical synthesis of human matrix Gla protein.

Human matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein that binds Ca2+ ions and that is involved in the prevention of vascular calcification. MGP is a 10.6-kD protein (84 amino acids) containing five gamma-carboxyglutamic acid (Gla) residues and one disulfide bond. Studies of the mechanism by which MGP prevents calcification of the arterial media are hampered by the low solubility of the protein (<10 microg/mL). Because of solubility problems, processing of a recombinantly expressed MGP-fusion protein chimera to obtain MGP was unsuccessful. Here we describe the total chemical synthesis of MGP by tBoc solid-phase peptide synthesis (SPPS) and native chemical ligation. Peptide Tyr1-Ala53 was synthesized on a derivatized resin yielding a C-terminal thioester group. Peptide Cys54-Lys84 was synthesized on Lys-PAM resin yielding a C-terminal carboxylic acid. Subsequent native chemical ligation of the two peptides resulted in the formation of a native peptide bond between Ala53 and Cys54. Folding of the 1-84-polypeptide chain in 3 M guanidine (pH 8) resulted in a decrease of molecular mass from 10,605 to 10,603 (ESI-MS), representing the loss of two protons because of the formation of the Cys54-Cys60 internal disulfide bond. Like native MGP, synthetic MGP had the same low solubility when brought into aqueous buffer solutions with physiological salt concentrations, confirming its native like structure. However, the solubility of MGP markedly increased in borate buffer at pH 7.4 in the absence of sodium chloride. Ca2+-binding to MGP was confirmed by analytical HPLC, on which the retention time of MGP was reduced in the presence of CaCl2. Circular dichroism studies revealed a sharp increase in alpha-helicity at 0.2 mM CaCl2 that may explain the Ca2+-dependent shift in high-pressure liquid chromatography (HPLC)-retention time of MGP. In conclusion, facile and efficient chemical synthesis in combination with native chemical ligation yielded MGP preparations that can aid in unraveling the mechanism by which MGP prevents vascular calcification.

Blotting, Western↗
PubMed2001

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

BACKGROUND: A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency. AIMS: To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density. METHODS: Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population. RESULTS: Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not. CONCLUSIONS: The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.

Absorptiometry, Photon↗
PubMed2001

Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques.

In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.

Adult↗
PubMed2001

Corn oil-induced decrease in arterial thrombosis tendency may be related to altered plasma vitamin K transport.

In this article we report the effects of low and high fat diets on the arterial thrombosis tendency in rats. The animal system used was the aorta loop model, in which we compared the effect of saturated (hardened coconut oil, HCO) and unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial thrombosis tendency at high fat intake (50 energy%, 45 energy% of which was either HCO, SSO, or CO). Under these conditions both SSO and CO had a beneficial effect (relative to HCO) on the arterial thrombosis tendency. In a subsequent study we compared these high fat diets with a low fat diet (5 energy%). As compared with the low fat diet, only CO significantly decreased the thrombosis risk. Serum vitamin K and triglycerides had decreased substantially after the CO diet, and to a much lesser extent after the SSO diet. It is concluded that corn oil may have a mildly anticoagulant effect, the potential benefit of which is discussed.

Animals↗
PubMed2000

Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors.

A mutation in the gamma-glutamyl carboxylase gene leading to a combined congenital deficiency of all vitamin K-dependent coagulation factors was identified in a Lebanese boy. He is the first offspring of consanguineous parents and was homozygous for a unique point mutation in exon 11, resulting in the conversion of a tryptophan codon (TGG) to a serine codon (TCG) at amino acid residue 501. Oral vitamin K(1) administration resulted in resolution of the clinical symptoms. Screening of several family members on this mutation with an RFLP technique revealed 10 asymptomatic members who were heterozygous for the mutation, confirming the autosomal recessive pattern of inheritance of this disease. In 50 nonrelated normal subjects, the mutation was not found. This is the second time a missense mutation in the gamma-glutamyl carboxylase gene is described that has serious impact on normal hemostasis.

Blood Coagulation Factors↗
PubMed2000

A comprehensive review of vitamin K and vitamin K antagonists.

For more than 60 years, vitamin K-dependent proteins have been known to play an important role in regulating blood coagulation. During recent years it has become clear, however, that vitamin K is also involved in other physiologic processes, including bone metabolism and vascular biology. Because the vitamin K requirement of bone and vessel wall is higher than that of the liver (where the clotting factors are produced) recommended daily allowance (RDA) values for K vitamins must be redefined. According to the new definition, a substantial part of the population is mildly deficient in vitamin K, and at later ages this deficiency may contribute to increased bone fracture risk, arterial calcification, and cardiovascular disease.

Blood Coagulation↗
PubMed2000

Patients' perceptions of seclusion: a qualitative investigation.

Twelve patients receiving acute in-patient psychiatric care in Queensland, Australia, participated in semi-structured interviews to elicit their perceptions of seclusion. All respondents had experienced time in seclusion within the 7 days prior to interview. Interviews were audiotaped, transcribed and analysed using content analysis. Five major themes emerged: use of seclusion, emotional impact, sensory deprivation, maintaining control and staff-patient interaction. The prevailing negativity towards seclusion underscores the need for ongoing critical review of its use. In particular, the relationship between patient responses to seclusion and the circumstances in which seclusion takes place requires greater consideration. Interventions such as providing information to patients about seclusion, increased interaction with patients during seclusion, attention to privacy and effective debriefing following seclusion may help to reduce the emotional impact of the practice.

Adaptation, Psychological↗