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H K Berthold

Publications and source records attributed to H K Berthold.

36 records · Page 2Linked to original sources
PubMed2000

Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase?

BACKGROUND: It has been suggested that the major metabolic block in the methionine catabolic pathway in cirrhotics exists at the level of the enzyme S-adenosylmethionine synthetase because in previous studies using conventional amino-acid analyzers, no intermediates of transmethylation/transsulfuration were found to accumulate in plasma downstream of S-adenosylmethionine synthesis. We therefore measured serum concentration intermediates of methionine transmethylation/transsulfuration using an improved gas chromatography/mass spectrometry technique. METHODS: Serum concentrations of methionine, homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, 2-methylcitric acid and alpha-aminobutyric acid were determined by gas chromatography/mass spectrometry in 108 consecutive patients with liver cirrhosis at Child stages A (mild cirrhosis, n = 27) and B/C (severe cirrhosis, n = 81), 18 outpatients with non-cirrhotic liver disease, and 55 healthy individuals. RESULTS: Serum levels of methionine, N,N-dimethylglycine, N-methylglycine, cystathionine, and homocysteine were significantly higher in patients at Child stages B/C compared with those of healthy controls (P < 0.01), and they were also significantly higher than in patients with non-cirrhotic liver disease (P < 0.01 and P < 0.05 for homocysteine, respectively). They also correlated with the Child-Pugh score (P < 0.01). Homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, and 2-methylcitric acid correlated with serum creatinine. The mean cystathionine concentration was significantly higher in patients with creatinine > or = 1.4 mg/dl than in patients with normal creatinine values (P < 0.01). However, the differences between cirrhotics and healthy controls were still significant after correcting for creatinine. CONCLUSIONS: Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction.

Adolescent↗
PubMed2000

Physiologic fluctuations of serum estradiol levels influence biochemical markers of bone resorption in young women.

We investigated the effect of physiologic variations in sex hormone levels during the menstrual cycle on biomarkers of bone turnover. Blood and 24-h and fasting urine samples were obtained in nine women (age, 25.1+/-3.0 yr) with regular menstrual cycles during the early follicular period (t1), 3 days before ovulation (t2), 3 days after ovulation (t3), at the midluteal period (t4) and again during the early follicular period of the next cycle (t5). All subjects had a calcium intake covering current dietary recommendations (above 1,000 mg/day, standardized food record). Serum calcium, phosphorus, calcitriol, 24-h and 2-h fasting urinary calcium, and phosphorus excretion remained constant during the menstrual cycle. Serum 25-hydroxyvitamin D3 levels decreased slightly from the beginning until the end of the study (P<0.05), indicating low cutaneous vitamin D synthesis during wintertime. The serum levels of sex hormones showed typical monthly variations, with the lowest estradiol (E2) levels at t1 and t5. Fasting 2-h pyridinoline (Pyd) concentrations (a marker of bone resorption) fell from t1 to t3 and rose again at t5 (P<0.01). Similar variations were observed for the resorption marker deoxypyridinoline (Dpd; P<0.05). The amplitude of the two biomarkers was 32% and 33%, respectively. The serum levels of the carboxyterminal propeptide of type I collagen (a marker of bone formation) showed an inverse cyclic pattern, as compared with the pyridinium cross-links. Low concentrations were observed at t1; a rise occurred until t3 and was followed by a decrease until t5 (P<0.05). A similar cyclic pattern was observed for serum PTH levels, with the highest concentrations at t3 (P<0.05). Dpd and Pyd values were significantly correlated with serum E2 levels (r = 0.52; P<0.0001 and r = 0.50; P<0.001, respectively). Neither progesterone nor LH nor FSH was correlated with Pyd or Dpd levels. The data suggest that normal menstrual cycling in young women is associated with monthly fluctuations in bone turnover. This physiological effect of the menstrual cycle is most probably related to variations in serum E2 concentrations.

Adult↗
PubMed1999

Influence of protease inhibitor therapy on lipoprotein metabolism.

OBJECTIVES: Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options. DESIGN: We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline. RESULTS: Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.) CONCLUSIONS: The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.

Adult↗
PubMed1998

Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: a randomized controlled trial.

CONTEXT: Garlic-containing drugs have been used in the treatment of hypercholesterolemia even though their efficacy is not generally established. Little is known about the mechanisms of action of the possible effects on cholesterol in humans. OBJECTIVE: To estimate the hypocholesterolemic effect of garlic oil and to investigate the possible mechanism of action. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Outpatient lipid clinic. PATIENTS: We investigated 25 patients (mean age, 58 years) with moderate hypercholesterolemia. INTERVENTION: Steam-distilled garlic oil preparation (5 mg twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. MAIN OUTCOME MEASURES: Serum lipoprotein concentrations, cholesterol absorption, and cholesterol synthesis. RESULTS: Baseline lipoprotein profiles were (mean [SD]): total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/ dL). Lipoprotein levels were virtually unchanged at the end of both treatment periods (mean difference [95% confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [-7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to 9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9] mg/dL), P=.20; triglycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to 12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%0], P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] microg/d, P=.78), and changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs 10.6% [21.1%], P=.62) were not different in garlic and placebo treatment. CONCLUSIONS: The commercial garlic oil preparation investigated had no influence on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic therapy for treatment of hypercholesterolemia cannot be recommended on the basis of this study.

Adult↗
PubMed1998

Garlic preparations for prevention of atherosclerosis.

On the basis of a number of new rigorously designed controlled studies, there is increasingly less evidence for lipid lowering properties of garlic preparations. Many other aspects of garlic drugs, such as direct effects on vessel walls (aortic elasticity, effects of antioxidant properties on early steps in atherosclerosis formation) or anti-platelet aggregation effects, are still awaiting further elucidation in clinical studies.

Animals↗
PubMed1997

Integration of amino acid and carbon intermediary metabolism: studies with uniformly labeled tracers and mass isotopomer analysis.

The central pathways of metabolism include glycolysis and gluconeogenesis, fatty acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because these pathways intersect, changes in one pathway, due to inborn error or disease, affect pathways that may seem remote from the initial metabolic defect. These metabolic interrelationships also present difficulties for isotopic studies, because once carbon derived from isotopic tracers is introduced into metabolism it is extensively recycled. The use of multiple labeled (especially uniformly 13C-labeled ([U-13C]), metabolic tracers, in conjunction with mass isotopomer distribution analysis of mass and nuclear magnetic spectra, has enabled the development of methods that resolve some of these difficulties. Suitable choices of tracers and analytes allow the simultaneous measurement of multiple pathways and, importantly, their kinetic interrelationships. We illustrate three uses of the technique: (1) the unequivocal determination of trace fluxes; (2) the quantification of biosynthetic pathways: and (3) the dissection, in vivo, of the citric acid (Krebs) cycle. In each case, different combinations of [U-13C]tracer and metabolic end product have revealed metabolic phenomena that otherwise would remain unidentified. A particularly striking, and unexpected, observation that has emerged from recent studies using the technique, suggests that the key dehydrogenase reactions in the Krebs cycle may be reversible. Although this approach is of relatively recent development, it has already given a number of novel insights into the organization of the central metabolic pathways. It should provide a powerful method of investigating the metabolic impact of genetic disease and provide invaluable support of the assessment of new therapeutic interventions.

Amino Acids↗
PubMed1997

Failure of the nonselective beta-blocker propranolol to affect lipoprotein lipase gene expression in the rat.

Treatment with beta-blockers has been reported to be associated with the development of hypertriglyceridemia. The etiology, even the existence, of this phenomenon is controversial. The purpose of our study was to examine whether the nonselective beta-blocker propranolol causes hypertriglyceridemia in the rat and whether its action is mediated by the modulation of lipoprotein lipase (LPL) messenger RNA (mRNA) accumulation or activity. LPL activity was assayed in fresh tissue by incubation with tritiated triglycerides. LPL mRNA was quantified in total RNA by slot-blot analysis using a mouse LPL complementary DNA probe. We have conducted three series of experiments in unanaesthetized rats in order to study the effects of different single doses of propranolol (1.5 to 6 mg i.p.) and different durations of treatment (15 min to 4 wk). We measured triglyceride and cholesterol levels in plasma as well as the LPL activity and mRNA levels in the heart and adipose tissue before and after propranolol administration. In these experiments we did not find any significant decrease in either the activity or the amount of mRNA of lipoprotein lipase nor was there any change in plasma lipids following treatment. Our results lead us to the conclusion that the nonselective beta-blocker propranolol affects neither the activity nor the mRNA level of LPL in the rat.

Adipose Tissue↗
PubMed1995

Evidence for incorporation of intact dietary pyrimidine (but not purine) nucleosides into hepatic RNA.

The absorption and metabolism of dietary nucleic acids have received less attention than those of other organic nutrients, largely because of methodological difficulties. We supplemented the rations of poultry and mice with the edible alga Spirulina platensis, which had been uniformly labeled with 13C by hydroponic culture in 13CO2. The rations were ingested by a hen for 4 wk and by four mice for 6 days; two mice were fed a normal diet and two were fed a nucleic acid-deficient diet. The animals were killed and nucleosides were isolated from hepatic RNA. The isotopic enrichment of all mass isotopomers of the nucleosides was analyzed by selected ion monitoring of the negative chemical ionization mass spectrum and the labeling pattern was deconvoluted by reference to the enrichment pattern of the tracer material. We found a distinct difference in the 13C enrichment pattern between pyrimidine and purine nucleosides; the isotopic enrichment of uniformly labeled [M + 9] isotopomers of pyrimidines exceeded that of purines [M + 10] by > 2 orders of magnitude in the avian nucleic acids and by 7- and 14-fold in the murine nucleic acids. The purines were more enriched in lower mass isotopomers, those less than [M + 3], than the pyrimidines. Our results suggest that large quantities of dietary pyrimidine nucleosides and almost no dietary purine nucleosides are incorporated into hepatic nucleic acids without hydrolytic removal of the ribose moiety. In addition, our results support a potential nutritional role for nucleosides and suggest that pyrimidines are conditionally essential organic nutrients.

Adenosine↗
PubMed1995

Isotopic evidence for the differential regulation of arginine and proline synthesis in man.

Arginine and proline derive from the metabolism of delta 1-pyrolline-5-carboxylate, a product of intestinal glutamic acid metabolism. We studied the extent of glutamate, arginine, and proline synthesis in four adult fed and fasted women. The subjects ingested a single dose of a mixture of uniformly (U)-13C-labeled amino acids and carbohydrate of algal origin. Frequent blood samples were taken for 24 hours. All the mass isotopomers of plasma lysine, glutamate + glutamine (GLX), arginine, and proline were measured using negative chemical ionization, selected-ion monitoring gas chromatography-mass spectrometry. In this isotopic approach, the appearance of U-13C-amino acid in the plasma reflects entry of the dietary amino acids, and the appearance of 13C in lower mass isotopomers demonstrates synthesis of the respective amino acids by the subject. All the mass isotopomers (including [M + 4]) of GLX became enriched with 13C. We suggest that the [M + 4] isotopomer of GLX reflects synthesis of the amino acid from alpha-ketoglutarate derived from the metabolism of U-13C-carbohydrate by the bacterial flora. Arginine labeling showed two patterns. The [M + 5] isotopomer of plasma arginine was labeled as rapidly as [M + 6] (ie, tracer) arginine, and we propose that the appearance of the [M + 5] isotopomer reflects the synthesis of citrulline from dietary [M + 5]-glutamate in first pass. The [M + 1] to [M + 3] isotopomers of arginine were also labeled for a prolonged period of time, suggesting that systemic glutamate was also a precursor for arginine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Estimates of the effect of feeding on whole-body protein degradation in women vary with the amino acid used as tracer.

We measured how feeding status affects the kinetics of multiple indispensable amino acids in four adult female subjects studied both in fed and fasted state. The subjects ingested one dose of uniformly 13C-labeled algae (Spirulina platensis). The isotopic enrichments (measured with negative chemical ionization gas chromatography-mass spectrometry) of the branched chain amino acids, phenylalanine, lysine and threonine were followed for 24 h in both the plasma and in VLDL-apolipoprotein B-100 (apoB-100). Fasting lowered body protein degradation when measured with the branched chain amino acids, increased it when measured with phenylalanine and had no statistically significant effect when determined from the kinetics of lysine and threonine. These apparent differences challenge the adequacy of current models of whole-body protein turnover. The ratio of the peak labeling of amino acids in plasma and apoB-100 was used as an estimate of the isotopic dilution in the hepatic pool. In contrast to our earlier observations during intravenous tracer amino acid administration, in the present study fasting lowered the ratio of the peak isotopic enrichments of apoB-100 and plasma amino acids. This supports our contention that feeding increases the use of hepatic portal amino acids for hepatic secretory protein synthesis.

Adult↗
PubMed1995

A novel stable isotope breath test: 13C-labeled glycosyl ureides used as noninvasive markers of intestinal transit time.

OBJECTIVES: Breath tests are widely used for diagnosis and control of treatment efficacy. There is a need for breath test substrates that reflect intestinal transit times under various conditions. METHODS: We synthesized a new class of breath test substrates, 13C-labeled glycosyl ureides, which are specific markers for the action of colonic microbial flora. We then investigated their usefulness as markers of intestinal transit time. RESULTS: Bolus ingestion of 1 g lactose or cellobiose 13C-ureide resulted in bacterial cleavage of the N-glycosyl bond and subsequent urea hydrolysis. 13CO2 appeared in breath and was determined by gas-isotope-ratio-mass spectrometry. Label first appeared after 5-6 h, peak excretion occurred between 8-14 h, and the signal returned to baseline after 18-24 h. Metoclopramide (10 mg) administered 1 h before the substrate advanced the onset of the signal by 2.4 +/- 1.95 h (mean +/- SD; n = 7; p < 0.05) and the time of peak response by 0.8 +/- 1.44 h. Loperamide (16 mg) broadened the peak and delayed the time of breath signal onset by 1.0 +/- 2.78 h and peak excretion by 4.0 +/- 3.7 h (p < 0.05). CONCLUSIONS: The glycosyl ureide breath test reflected intestinal transit time and rapid changes in gastrointestinal motility. This test should be useful in the diagnosis of a variety of gastrointestinal motility disorders and in the development of drugs that affect gastrointestinal motility.

Adolescent↗
PubMed1994

Leucine oxidation changes rapidly after dietary protein intake is altered in adult women but lysine flux is unchanged as is lysine incorporation into VLDL-apolipoprotein B-100.

We measured the 13C enrichments of expired CO2 and deuterium enrichments of plasma free lysine and VLDL-apolipoprotein B-100 in five nulliparous women who received an oral bolus dose of [1-13C]leucine and a primed, constant infusion of [2H4]lysine on d 2 and 6 while consuming protein diets of 1.5, 1.0 and 0.4 g.kg-1 x d-1. Peak enrichments and cumulative percent recoveries of 13C in expired CO2 increased during the high, and decreased during the low protein periods within 24 h of altered intakes; these changes averaged 89% of that on d 6 of the high and low protein diets. The early changes in leucine oxidation showed significant relationships with urinary nitrogen excretion on d 6 of the dietary periods. The ratio of the isotopic enrichment of lysine in VLDL-apolipoprotein B-100 to that in plasma was unaltered by the level of protein intake. Thus, amino acid oxidation adapts rapidly to altered protein intakes in adult women and is useful to determine protein needs during rapidly changing physiologic conditions. However, 6-d periods of protein intake over the range of 1.5 to 0.4 g.kg-1 x d-1 do not affect the proportional use of dietary amino acids for hepatic secretory protein synthesis.

Administration, Oral↗
PubMed1991

Uniformly 13C-labeled algal protein used to determine amino acid essentiality in vivo.

The edible alga Spirulina platensis was uniformly labeled with 13C by growth in an atmosphere of pure 13CO2. The labeled biomass was then incorporated into the diet of a laying hen for 27 days. The isotopic enrichment of individual amino acids in egg white and yolk proteins, as well as in various tissues of the hen at the end of the feeding period, was analyzed by negative chemical ionization gas chromatography/mass spectrometry. The amino acids of successive eggs showed one of two exclusive enrichment patterns: complete preservation of the intact carbon skeleton or extensive degradation and resynthesis. The same observation was made in tissue proteins. These patterns were cleanly divided according to known nutritional amino acid essentiality/nonessentiality but revealed differences in labeling among the nonessential amino acids: most notable was that proline accretion was derived entirely from the diet. Feeding uniformly 13C-labeled algal protein and recovering and analyzing de novo-synthesized protein provides a useful method to examine amino acid metabolism and determine conditional amino acid essentially in vivo.

Journal Article↗
PubMedDate not supplied

Immunoglobulins and IgG subclasses in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Serum immunoglobulin levels and distribution are altered in patients with inflammatory bowel disease (IBD). The purpose of this study is to examine the value of serum concentration of IgG subclasses for the diagnosis and evaluation of disease activity of IBD and to assess possible differences in the immunoglobulin changes between patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODOLOGY: We measured serum IgG and IgG subclasses concentrations as well as IgA, IgM, ESR, CRP, elastase levels and granulocyte count of 96 patients with chronic IBD (69 with CD and 27 with UC) with various levels of disease activity. RESULTS: The total IgG levels in patients with UC were significantly increased, for both active and inactive disease, compared to those of patients with CD. The IgG1 concentration in patients with UC (7+/-0.77 mg/ml) was significantly higher than in patients with CD (5.6+/-0.61 mg/ml) (p<0.02). The IgG2 levels in CD were significantly higher than those of UC (4.6+/-0.64 vs. 3.8+/-0.57 mg/ml) (p<0.05). The IgG4 levels of UC patients were significantly higher than those of the CD patients (0.39+/-0.06 vs. 0.29+/-0.05 mg/ml) (p<0.05). No significant differences were found in the serum concentrations of IgG3, IgA and IgM between the two groups. There was a negative correlation between the various indices of disease activity and the concentration of IgG3 in patients with UC (p<0.01), and a positive correlation in patients with CD for IgG1 (p<0.001), IgG2 (p<0.001) and IgA (p<0.01). CONCLUSIONS: In IBD some of the IgG immunoglobulin subclass concentration changes correlate, positively or negatively, with disease activity and therefore could be used as additional markers of it. However, serum immunoglobulin levels cannot be used to differentiate between UC and CD.

Adult↗
PubMedDate not supplied

Neutrophil-elastase in chronic inflammatory bowel disease: a marker of disease activity?

BACKGROUND/AIMS: Neutrophil elastase is a proteinase which exists in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. In inflammatory bowel disease there is a leukocyte infiltration of the bowel mucosa. The purpose of this study was to examine whether plasma elastase represents a reliable laboratory marker for establishing the activity of chronic inflammatory bowel disease. METHODOLOGY: We measured plasma elastase concentrations in 61 patients suffering from either Crohn's disease or ulcerative colitis and compared these data with other clinical and laboratory findings and with elastase concentrations in 40 healthy controls. The sensitivity and specificity of the elastase values in chronic IBD were calculated with the use of concomitant measurements of CRP and ESR. RESULTS: Plasma levels were found to be significantly higher in patients (49 micrograms/l) compared with healthy controls (23 micrograms/l). Patients with active disease had higher plasma levels than patients in remission. In general, the sensitivity of elastase to detect active inflammatory bowel disease was about 60%; the specificity was 65%. For patients in remission, the sensitivity was higher than 80%. However, there was a wide range of overlapping values between chronic inactive patients and those with moderately active disease. CONCLUSIONS: We conclude that plasma elastase is a useful independent marker of disease activity in inflammatory bowel disease. Especially for identifying patients in remission, the measurements of elastase seem to be more suitable than other parameters of inflammation, like CRP or ESR.

Adult↗