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Biomedical subjects

S Westphal

Publications and source records attributed to S Westphal.

At least 19 recordsLinked to original sources

Post-hoc analysis on the CD14 C(-260)T promoter polymorphism and coronary heart disease.

Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.

Aged↗

Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab.

In contrast to focal segmental glomerulosclerosis, which is well known to recur early in a renal graft, there are only few cases described with recurrence of immunoglobulin M (IgM) nephropathy after transplantation. We herein describe a patient with early recurrence of IgM nephropathy. A 15-year-old boy with nephrotic syndrome (IgM nephropathy) proceeding to end-stage renal disease was on dialysis before living related renal transplantation. Native kidneys were not removed. Standard immunosuppression including steroids, tacrolimus, and mycophenolate mofetil yielded initially good graft function with the s-creatinine falling to 73 micromol/L. Proteinuria was present on day 1, increasing to 20 g/L after 3 days. S-creatinine increased to 158 micromol/L and urine production diminished. A graft biopsy showed no rejection or glomerulopathy but protein vacuoles were seen within tubular cells indicating massive proteinuria. Treatment with plasma exchanges, immunoglobulin, and steroids was started. Hemodialysis was necessary. Proteinuria improved to 3.5 g/L, but s-creatinine continued to rise and a second graft biopsy showed vascular rejection (Banff type IIA). The patient was treated with antithymocyte globulin and further plasma exchanges. A single dose of rituximab was given. Five months after transplantation the s-creatinine was 67 micromol/L and there was no proteinuria. In this case early recurrence of nephrotic syndrome occurred on the first posttransplant day in combination with later occurring vascular rejection. Successful treatment included a combination of plasma exchanges, rituximab, immunoglobulin, and antithymocyte globulin.

Adolescent↗

Endocrine and behavioural plasticity in response to juvenile stress in the semi-precocial rodent Octodon degus.

The present study in the South American rodent Octodon degus shows for the first time that the postnatal development of hypothalamic-pituitary-adrenal axis function in this semi-precocial species differs from that of altricial rodents, i.e. rats or mice, in several aspects. Our experiments revealed a particular pattern of hypothalamic-pituitary-adrenal axis activity during the first 3 weeks of life characterized by (i) a period of low plasma glucocorticoid concentrations, during which (ii) brief stress exposure (1 h parental separation) is able to elevate glucocorticoids significantly. In addition, (iii) repeated stress exposure (1 h parental separation daily) during the first 3 weeks of life resulted in females, but not in males, in an attenuated separation-induced increase of glucocorticoids, and a higher behavioural activity in both sexes at postnatal day 21. These data indicate that parental separation early in life acts as a 'strong' stressor in this species, which on the long run can alter endocrine stress response at the time of weaning in a sex-specific manner. These findings support the role of the hypothalamic-pituitary-adrenal axis as one of the key factors mediating the effects of early life stress on the neuronal network and behaviour in O. degus.

Acute Disease↗

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations.

BACKGROUND: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. OBJECTIVES: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. DESIGN: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies. RESULTS: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years). CONCLUSIONS: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

Adult↗

Detection of recent ethanol intake with new markers: comparison of fatty acid ethyl esters in serum and of ethyl glucuronide and the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid in urine.

BACKGROUND: At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. METHODS: Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. RESULTS: The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean +/- SD, 30.1 +/- 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. CONCLUSION: After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr.

Adult↗

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells.

Four patients with chronic myelogenous leukemia (CML) that was refractory to interferon alpha (two patients) or imatinib mesylate (two patients), and who lacked donors for allogeneic stem cell transplantation, received autotransplants followed by infusions of ex vivo costimulated autologous T cells. At day +30 (about 14 days after T-cell infusion), the mean CD4+ cell count was 481 cells/microl (range 270-834) and the mean CD8+ count was 516 cells/microl (range 173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell infusion, with CD4 and CD8 levels of 750 and 1985 cells/microl, respectively. All the four patients had complete cytogenetic remissions early after transplantation, three of whom also became PCR negative for the bcr/abl fusion mRNA. One patient, who had experienced progressive CML while on interferon alpha therapy, became PCR- post transplant, and remained in a molecular CR at 3.0 years of follow-up. All the four patients survived at 6, 9, 40, and 44 months post transplant; the patient who remained PCR+ had a cytogenetic and hematologic relapse of CML, but entered a molecular remission on imatinib. Autotransplantation followed by costimulated autologous T cells is feasible for patients with chronic phase CML, who lack allogeneic donors and can be associated with molecular remissions.

Adoptive Transfer↗

Tomato profilin Lyc e 1: IgE cross-reactivity and allergenic potency.

BACKGROUND: To date, very little data are available about the nature of tomato allergens. Immunoglobulin E (IgE) cross-reactive profilins have been suggested to account for allergic symptoms in patients suffering from tomato allergy. METHODS: The cDNA of tomato profilin was amplified by reversely transcribed polymerase chain reaction (RT-PCR) from total RNA extracted from ripe tomato fruit. The gene was cloned into the pET101D expression plasmid and the protein was produced in Escherichia coli BL21. Purification was performed via poly-l-proline (PLP) affinity chromatography. IgE reactivity of recombinant tomato profilin was investigated by immunoblot and enzyme-linked immunosorbent assay. IgE-inhibition studies were performed to analyse cross-reactivity with other profilins. To determine the allergenic activity of the recombinant protein, basophil histamine release assays using sera of patients with adverse reactions to tomato were performed. RESULTS: Profilin was identified as a new minor allergen in tomato fruits. The recombinant tomato profilin comprises 131 amino acids and high sequence identity to other allergenic food and pollen profilins. It was shown to be IgE-reactive with a prevalence of 22% (11/50) in tomato-allergic patients. In patients with tomato allergy and multiple sensitization to other foods and birch pollen, IgE directed against tomato profilin showed a strong cross-reactivity with profilins from plant food sources and birch pollen. The tomato profilin was able to induce mediator release from human basophils. CONCLUSION: The tomato profilin is a minor allergen in tomato fruit. Thus, it shows biological activity, as confirmed by in vitro histamine release assays with human basophils and thereby has the potential to account for clinical symptoms in tomato-allergic patients.

Adult↗

Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells.

Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

Adenocarcinoma↗

Influence of preapheresis clinical factors on the efficiency of CD34+ cell collection by large-volume apheresis.

We evaluated 120 leukapheresis procedures (93 patients), in order to detect clinical factors that influence the efficiency of CD34+ collection using Cobe Spectra trade mark cell separators. Hematocrit was >27% and platelet count >30 000/microl in >95% of patients. Platelet transfusions were given if the postprocedure count was &<20 000/microl. Multiple regression analysis was used to analyze putative factors, and a predictive equation defined by stepwise regression modeling. The mean efficiency was 0.59 (s.d. 0.27). Sex (M>F; P=0.01), the volume processed (inversely; P=0.01) and CD34+ cell count (inversely; P=0.04) were associated with efficiency, whereas hematocrit, platelet or leukocyte count, catheter type and patient weight were not. The effect size for predictive factors was small (R(2)=0.21). Adverse events were limited to hypocalcemia. We conclude that female sex, volume processed and CD34+ cell count adversely influence the efficiency of CD34+ cell leukapheresis. However, the impact of volume and CD34+ cell count is small, and likely to be offset by the influence of these same factors on overall yield. Leukapheresis appears to be safe and efficient for autologous blood and marrow transplantation patients with hematocrit >27% and platelet count >30 000/microl.

Antigens, CD34↗

Treatment of paediatric pontine glioma with oral trophosphamide and etoposide.

To evaluate the overall survival of paediatric patients with pontine gliomas treated with oral trophosphamide and etoposide. Patients between 3 and 17 years of age with either typical diffuse pontine glioma on MRI or histologically proven anaplastic astrocytoma/glioblastoma multiforme located in the pons, were eligible. Treatment consisted of oral trophosphamide 100 mg x m(-2) x day(-1) combined with oral etoposide at 25 mg x m(-2) x day(-1) starting simultaneously with conventional radiation. Twenty patients were enrolled (median age 6 years, male : female=9 : 11). Surgical procedures included: no surgery: five, open biopsy: three, stereotactic biopsy: six, partial resection: three, and sub-total resection: three. Histological diagnoses included pilocytic astrocytoma: one, astrocytoma with no other specification: three, anaplastic astrocytoma: three, glioblastoma multiforme: eight, no histology: five. The most frequent side effects were haematologic and gastrointestinal. There was no toxic death. The response to combined treatment in 12 evaluable patients was: complete response: 0, partial response: three, stable disease: four, and progressive disease: five. All tumours progressed locally and all patients died. The overall median survival was 8 months. The overall survival rates at 1 and 4 years were: 0.4 and 0.05 respectively. This was not different from a control group of patients documented in the same population. Oral trophosphamide in combination with etoposide did not improve survival of pontine glioma patients. The treatment was well tolerated and should be evaluated for more chemoresponsive paediatric malignancies.

Administration, Oral↗

Addition of glucose to a fatty meal delays chylomicrons and suppresses VLDL in healthy subjects.

BACKGROUND: Postprandial lipemia has been shown in a number of studies to be associated with atherosclerosis. However, the test meals used in these studies were heterogeneous particularly in their carbohydrate content, which may be important for the resulting lipemia and which makes comparison between different studies difficult. We studied the effect of 75 g glucose added to a fatty meal on various lipoproteins and on gastric emptying. MATERIALS AND METHODS: Fourteen healthy young volunteers were studied in the fasting state and until 7 h postprandially. In a crossover design, each subject received an oral fat load (1 g fat kg(-1) body weight) with or without 75 g glucose. Triacylglycerol (TG) and free fatty acids (FFA) were then measured in whole blood and lipoproteins were separated off by ultracentrifuging. Gastric emptying was determined by the (13)C breath test. RESULTS: The addition of 75 g glucose to a fatty meal had two different effects. Gastric emptying was delayed by about 2 h and the chylomicron response was consequently postponed. In addition, the postprandial increase in VLDL triacylglycerol was reduced by 40%, which may be due to the pronounced FFA depression during the glucose-induced rise in insulin. CONCLUSIONS: 75 g glucose added to an oral fat load causes a delay of the chylomicron response and a marked suppression of the postprandial increase in VLDL.

Adult↗

A vesicle transport system inside chloroplasts.

Intracellular transport via membrane vesicle traffic is a well known feature of eukaryotic cells. Yet, no vesicle transport system has been described for prokaryotes or organelles of prokaryotic origin, such as chloroplasts and mitochondria. Here we show that chloroplasts possess a vesicle transport system with features similar to vesicle traffic in homotypic membrane fusion. Vesicle formation and fusion is affected by specific inhibitors, e.g. nucleotide analogues, protein phosphatase inhibitors and Ca2+ antagonists. This vesicle transfer is an ongoing process in mature chloroplasts indicating that it represents an important new pathway in the formation and maintenance of the thylakoid membranes.

Biological Transport↗

Effects of fenofibrate and gemfibrozil on plasma homocysteine.

Fenofibrate increases plasma homocysteine. Because the concentration of plasma homocysteine depends on renal function, we postulate that increases in plasma homocysteine are a result of the known impairment of renal function caused by fenofibrate. Gemfibrozil, another fibrate, does not affect renal function. In a crossover study we tested whether gemfibrozil would raise homocysteine. 22 patients who had hypertriglyceridaemia were given 900 mg gemfibrozil or 200 mg fenofibrate daily for 6 weeks. Lipids were altered similarly, but homocysteine, creatinine, and cystatin C were raised by fenofibrate but not by gemfibrozil (p for differences between treatment effects: 0.007, 0.006, and 0.040, respectively). We propose gemfibrozil should be the fibrate of choice.

Adult↗

VIPP1, a nuclear gene of Arabidopsis thaliana essential for thylakoid membrane formation.

The conversion of light to chemical energy by the process of photosynthesis is localized to the thylakoid membrane network in plant chloroplasts. Although several pathways have been described that target proteins into and across the thylakoids, little is known about the origin of this membrane system or how the lipid backbone of the thylakoids is transported and fused with the target membrane. Thylakoid biogenesis and maintenance seem to involve the flow of membrane elements via vesicular transport. Here we show by mutational analysis that deletion of a single gene called VIPP1 (vesicle-inducing protein in plastids 1) is deleterious to thylakoid membrane formation. Although VIPP1 is a hydrophilic protein it is found in both the inner envelope and the thylakoid membranes. In VIPP1 deletion mutants vesicle formation is abolished. We propose that VIPP1 is essential for the maintenance of thylakoids by a transport pathway not previously recognized.

Amino Acid Sequence↗

Vipp1 deletion mutant of Synechocystis: a connection between bacterial phage shock and thylakoid biogenesis?

Plant chloroplasts originated from an endosymbiotic event by which an ancestor of contemporary cyanobacteria was engulfed by an early eukaryotic cell and then transformed into an organelle. Oxygenic photosynthesis is the specific feature of cyanobacteria and chloroplasts, and the photosynthetic machinery resides in an internal membrane system, the thylakoids. The origin and genesis of thylakoid membranes, which are essential for oxygenic photosynthesis, are still an enigma. Vipp1 (vesicle-inducing protein in plastids 1) is a protein located in both the inner envelope and the thylakoids of Pisum sativum and Arabidopsis thaliana. In Arabidopsis disruption of the VIPP1 gene severely affects the plant's ability to form properly structured thylakoids and as a consequence to carry out photosynthesis. In contrast, Vipp1 in Synechocystis appears to be located exclusively in the plasma membrane. Yet, as in higher plants, disruption of the VIPP1 gene locus leads to the complete loss of thylakoid formation. So far VIPP1 genes are found only in organisms carrying out oxygenic photosynthesis. They share sequence homology with a subunit encoded by the bacterial phage shock operon (PspA) but differ from PspA by a C-terminal extension of about 30 amino acids. In two cyanobacteria, Synechocystis and Anabaena, both a VIPP1 and a pspA gene are present, and phylogenetic analysis indicates that VIPP1 originated from a gene duplication of the latter and thereafter acquired its new function. It also appears that the C-terminal extension that discriminates VIPP1 proteins from PspA is important for its function in thylakoid formation.

Amino Acid Sequence↗

An improved method for the rapid assessment of persisting chylomicron remnant concentrations.

Persisting chylomicron remnant concentrations have been linked to premature atherosclerosis. The analysis of persisting chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. We describe major improvements of the testing procedure in regard of composition of the fatty meal, of patient testing, and measurement of postprandial remnants. Shifting the time of the (ready-to-use) fatty drink from the morning hours to bedtime was well accepted by the study subjects and allowed the analysis of blood samples drawn at the morning with minimal impact on the participants' time and with minimal interferences by confounding factors (e.g. smoking, additional food intake, physical activity). Chylomicron remnants were measured by fluorometry of the supernatant after ultracentrifugation. This procedure was sensitive, was specific for chylomicron remnants, and was easy to perform. The biological validity of the improved procedure was evaluated by studying type III hyperlipoproteinemia patients and normolipemic apolipoprotein (Apo) E2 homozygotes. In conclusion, this improved test permits the rapid testing for persisting chylomicron remnants in the clinical routine and in large epidemiological studies.

Adult↗

Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate.

Elevated homocysteine concentrations are a risk factor for atherosclerotic disease. Recently it was reported that lipid lowering with fibrates increases homocysteine by up to 40%. Since elevated homocysteine concentrations can readily be lowered by vitamin supplementation, a randomized, double-blind crossover study was performed to investigate the effect of fenofibrate plus folic acid, vitamin B6 and B12 versus fenofibrate plus placebo in hyperlipidemic men. The crossover study comprised a run-in period of 6 weeks, a first treatment phase of 6 weeks, a washout phase of 8 weeks and a second treatment phase of 6 weeks. Vitamins were given at doses of 650 microg folic acid, 50 microg vitamin B12 and 5 mg vitamin B6 per day for a period of 6 weeks. After fenofibrate plus placebo the increase in homocysteine concentration was 44+/-47%. After fenofibrate plus vitamins it was 13+/-25%, being significantly lower than without vitamins. The increase in homocysteine in response to fenofibrate may counteract the cardioprotective effect of lipid lowering. The addition of vitamins involved in homocysteine metabolism can prevent most of the homocysteine increase seen after fenofibrate plus placebo. Addition of these vitamins to fenofibrate may therefore be warranted for routine use.

Cross-Over Studies↗

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study.

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Adult↗