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Biomedical subjects

H K Berthold

Publications and source records attributed to H K Berthold.

At least 19 recordsLinked to original sources
PubMed2004

Lymphocyte proliferation and apoptosis in HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate rich in polyphenols and antioxidant vitamins.

OBJECTIVE: We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive (HIV(+)) and HIV-seronegative (HIV(-)) subjects. DESIGN: Randomized, prospective pilot intervention study. SETTING: University of Bonn, Department of General Internal Medicine. SUBJECTS: A total of 23 HIV(+) subjects from the HIV outpatient clinic, 18 HIV(-) controls. INTERVENTIONS: Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet. Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline, during 16-weeks of intervention, and after a 6-week washout. Proliferation was assessed by (3)H-thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry. RESULTS: Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation (mitotic index) in HIV(+) patients from 18+/-16 to 40+/-34 (P=0.004) and in healthy controls from 27+/-16 to 51+/-21 (P=0.016). Apoptosis was not affected in HIV(+) patients, but rose in healthy controls from 9+/-10 to 34+/-11 (apoptotic index; P=0.001). Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV(+) and HIV(-) subjects. CONCLUSIONS: Even though apoptosis did not change in HIV(+) subjects, ingestion of polyphenol-rich fruit juices might be favorable to HIV(+) patients due to enhanced proliferation, which could restore disturbances in T-cell homeostasis. In healthy controls, increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis.

Adult↗
PubMed2004

Lipoprotein metabolism in patients with anorexia nervosa: a case-control study investigating the mechanisms leading to hypercholesterolaemia.

Hypercholesterolaemia is a common finding in patients with anorexia nervosa (AN). To investigate the type, frequency and pathophysiological mechanisms of changes in lipoprotein metabolism in AN we performed a cross-sectional study in fifty-eight female patients (mean age 24.2 years, BMI 15.3 (sd 1.5) kg/m(2)) and fifty-eight healthy age-matched controls (CO; BMI 22.2 (sd 1.7) kg/m(2)). Total cholesterol and LDL-cholesterol were higher in AN (5.5 (sd 1.3) v. 5.0 (sd 0.8) mmol/l, P=0.023; 3.6 (sd 1.1) v. 3.2 (sd 0.7) mmol/l, P=0.025 respectively). LDL particles were significantly more enriched in cholesterol and triacylglycerol in AN. In multiple regression analysis with LDL-cholesterol as the dependent and BMI, total body fat ( %), lathosterol:cholesterol ratio (endogenous cholesterol synthesis), 7alpha-hydroxy-4-cholesten-3-one (bile acid synthesis), non-esterified glycerol, free triiodothyronine and free thyroxine as independent variables, BMI was the only significant predictor in CO (R(2) 0.36, overall P=0.001). In AN the variability of LDL-cholesterol was significantly predicted by total body fat, free thyroxine, BMI, free triiodothyronine and non-esterified glycerol (R(2) 0.55, overall P<0.001). Subgroup analysis between restricting (AN-R) and binge-eating-purging patients (AN-B) indicated that in AN-R changes in lipoproteins, BMI and total body fat were more pronounced. AN-R patients had lower bile acid synthesis than AN-B (P=0.02). We conclude that elevated cholesterol concentrations in AN are generally due to an increase in LDL-cholesterol, which is mostly determined by the severe loss of body fat and the resulting changes in thyroid hormones, increased lipolysis and decreased endogenous cholesterol synthesis with resulting decrease in LDL removal. The clinical subtype of AN plays a major role in the mechanisms leading to hypercholesterolaemia.

Adolescent↗
PubMed2003

Carbamazepine does not alter biochemical parameters of bone turnover in healthy male adults.

It is still not completely clear whether or not carbamazepine (CBZ) causes alterations in vitamin D status and in bone metabolism. The objective of this study was therefore to investigate prospectively in healthy adults the effects of CBZ on serum levels of 25-hydroxyvitamin D (25OHD) and on biomarkers of bone formation and resorption. Twenty-one free-living male adults were taking 800 mg/day CBZ for 10 weeks. The study was performed from December 1997 until September 1998 at a geographic latitude of 51 degrees N. Blood samples were collected before treatment (t1), 33 days (SE 2.5) after starting treatment (t2), and 70 days (SE 3.6) after starting treatment (t3). In 13 out of the 21 subjects blood samples were also drawn 64 days (SE 9.0) after treatment had been terminated (t4). Serum 25OHD levels remained constant during study periods t1-t3. 25OHD levels were, however, significantly higher at t4 compared to t1-t3. Serum concentrations of intact osteocalcin, a bone formation marker, and C-telopeptide, a bone resorption marker, were similar during all examinations. Moreover, serum levels of parathyroid hormone, calcium, and inorganic phosphate did not change. Data indicate that CBZ per se does not alter bone metabolism and does not lead to decreased circulating 25OHD levels in young males without epilepsy. Variations in 25OHD levels are in line with the seasonal fluctuations in vitamin D status.

Administration, Oral↗
PubMed2003

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case-control study.

OBJECTIVE: To characterize the influence of body mass index (BMI), body composition, hormonal factors and disease duration on bone metabolism markers in anorexia nervosa (AN) patients. DESIGN: Case-control study with 51 AN patients and 51 controls matched for age, sex and body height. Assessment of anthropometric and bioimpedance data, and of biochemical serum parameters and of oral contraceptives use. RESULTS: Patients had a lower BMI, lower fat mass, lower fat-free mass and lower muscle mass (MM) compared to the controls (all P values <0.001). Moreover, serum levels of osteocalcin (bone formation marker) were lower while serum C-telopeptide concentrations (CTx; bone resorption marker) and the CTx/osteocalcin ratio (an index reflecting the balance of bone remodeling) were higher in the AN patients compared to the controls (P<0.01-0.001). In addition, patients had enhanced serum calcium and cortisol levels and reduced serum levels of thyroid hormones, insulin, and leptin (P values <0.05-0.001). Mean disease duration was 91+/-13 months. In a multiple regression analysis, BMI (P<0.0001), MM (P<0.005) and duration of the disease (P<0.005) were independent predictors of the CTx/osteocalcin ratio in the AN patients. There was a nonlinear association between BMI and the CTx/osteocalcin ratio of r=-0.72 (P<0.001) in the AN patients, but only a weak relation of r=-0.27 (P<0.05) between these parameters in the control subjects. Use of oral contraceptives had no effect on the CTx/osteocalcin ratio, neither in AN patients nor in controls. CONCLUSIONS: Data indicate an uncoupling of bone formation and bone resorption in AN, which is primarily the result of a low BMI and influenced by the duration of the disease.

Adolescent↗
PubMed2002

Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion.

BACKGROUND: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion. AIMS: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol. SUBJECTS: Six healthy, male volunteers. METHODS: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples. RESULTS: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028). CONCLUSION: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.

Adult↗
PubMed2002

Isotopomer spectral analysis of intermediates of cholesterol synthesis in human subjects and hepatic cells.

Steroid intermediates of the cholesterol synthesis pathway are characterized by rapid turnover rates relative to cholesterol due to their small pool size. Because the small pools will label rapidly, these intermediates may provide valuable information about the incorporation of isotopes in de novo synthesis of cholesterol and related compounds. The labeling of cholesterol synthesis intermediates from [1-(13)C]acetate was investigated in human subjects and in liver cell models by means of isotopomer spectral analysis (ISA). In human subjects, infusing [1-(13)C]acetate into the duodenum for 12 h demonstrated that approximately 50% of the plasma lathosterol pool was derived from de novo synthesis during this interval. The lipogenic acetyl-CoA precursor pool enrichment reached a constant value within 3 h of the start of the infusion. In vitro studies indicated that liver cell models decrease de novo lathosterol synthesis when cholesterol synthesis is inhibited by statins or cholesterol-containing serum. We propose a new calculation to increase the accuracy and precision of cholesterol synthesis estimates in vivo combining the ISA of lathosterol and cholesterol.

Acetates↗
PubMed2001

Oral contraceptives moderately effect bone resorption markers and serum-soluble interleukin-6 receptor concentrations.

This study investigated the effect of ethinylestradiol(EE2)-containing oral contraceptives on mineral and bone metabolism and on serum soluble-interleukin-6-receptor (sIL-6R) during the menstrual cycle. Twelve women, aged 24.3 +/- 2.9 years, were examined. Blood and 24-hour and fasting urine samples were obtained during one menstrual cycle between cycle day 3-5 (t(1)), cycle day 10-12 (t(2)), cycle day 24-26 (t(3)), and again on day 3-5 of the next cycle (t(4)). EE2 intake was 0 mg at t(1), 30 mg at t(2), 30 mg at t(3) and 0 mg at t(4). Fasting renal phosphorus and calcium excretions were slightly reduced at t(2) and t(3) compared with t(1) and t(4) (P < 0.05-0.001). Moreover, renal excretion of the bone resorption marker C-Teleopeptide was at t(3) reduced by 26% compared with t(1)(P < 0.01) and by 13% compared with t(4)(P > 0.05). Fasting sIL-6R levels were 16.5% lower at t(2) and 12% lower at t(3) than at t(4) (P < 0.01 and P < 0.05). sIL-6R was correlated with total deoxypyridinoline excretion (r = +0.35; P < 0.05) and with fasting renal excretions of calcium (r = +0.36; P < 0.05) and phosphorus (r = +0.29; P < 0.05). In summary, our data suggest that in young women, cyclic monthly oral contraceptive intake is associated with small, but significant variations in bone resorption processes and in serum sIL-6R levels. Results are a further indication that monthly fluctuations of bone resorption in young women are mediated by sex hormones and that osteoclastic activity is stimulated by cytokines in vivo.

Adult↗
PubMed2001

Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway.

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands thiazolidinediones have been reported to induce apoptosis in macrophages and in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis in VSMC, cultured rat VSMC were treated with increasing doses of the thiazolidinedione analogues troglitazone (TRO) and rosiglitazone (RSG). Both ligands induced cell death in a concentration-dependent manner (EC50 12.1+/-3.3 microM and 1.43+/-0.39 microM, respectively), causing almost complete cell death at the highest concentrations (100 microM and 10 microM for TRO and RSG, respectively), along with an expected parallel decrease in [3H]thymidine uptake into cell DNA (EC50 6.7+/-2.4 microM and 0.75+/-0.19 microM, respectively). The cell count was determined by the coulter counter principle. Furthermore two apoptotic markers were measured, the caspase 3 activity and the cytoplasmic histone-associated DNA fragments, both of which were significantly increased when the aforementioned high concentrations were used. This indicates that apoptosis is involved in the TRO- and RSG-induced VSMC growth suppression. The same concentrations of TRO and RSG caused an unexpected stimulation of the extracellular signal-regulated response kinases 1 and 2 (ERK1/2) and stimulated the p38 mitogenic-activated protein (MAP) kinase as determined by Western blotting. In order to establish whether the proapoptotic effects of TRO and RSG are mediated through ERK1/2 activation, we used the selective MAP kinase kinase (MEK) inhibitor PD98059 (20 microM), which suppressed the TRO- and RSG-induced ERK1/2 activation but did not abolish their proapoptotic effects. We conclude that the thiazolidinedione analogues TRO and RSG induce cell death due to apoptosis in VSMC through an ERK1/2-independent pathway.

Animals↗
PubMed2001

Effects of authentic and VLDL hydrolysis-derived fatty acids on vascular smooth muscle cell growth.

There are contradictory findings regarding the effects of free fatty acids on vascular smooth muscle cell (VSMC) growth. In the present study we investigated the effects of fatty acids released from hydrolysis of human VLDL triglycerides by lipoprotein lipase and of the fatty acids most abundant in the hydrolysed VLDL, namely oleic, linoleic, palmitic and myristic acid, all non albumin-bound, on VSMC growth. The effect of fatty acids on VSMC growth was assessed by [(3)H]-thymidine incorporation, colourimetrically, by cell counting, by determination of the cytoplasmic histone-associated DNA fragments and the caspase 3 activity. The fatty acid concentrations were determined by gas chromatography-mass spectrometry. Stimulation of ERK1/2 and p38 was determined by the chemiluminescence Western blotting method. Incubation of VSMC with purified VLDL (100 microg ml(-1)) and lipoprotein lipase (35 u ml(-1)) led to almost complete cell death although the ERK1/2 and the p38 MAP kinases were stimulated. The EC(50) of oleic, linoleic, myristic and palmitic acid were 4.6+/-1.3, 2.4+/-0.2, 116+/-10 and 287+/-30 microM, respectively. The estimated EC(50) of myristic and palmitic acid when derived from hydrolysed VLDL were 10 and 8 times, respectively, lower than when used alone. Apoptosis was not involved in the fatty acid-induced VSMC growth suppression/death. We conclude that (a) non albumin-bound fatty acids cause VSMC necrosis in a dose-dependent manner with a parallel ERK1/2 and p38 stimulation, (b) unsaturated fatty acids are more toxic to VSMC than saturated, and (c) saturated fatty acids are more toxic to VSMC in the hydrolysed VLDL than when used individually.

Animals↗
PubMed2001

Plasma antioxidant capacity of HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate containing antioxidant polyphenols.

OBJECTIVE: To investigate whether antioxidant polyphenols from fruit juices or a fruit-vegetable-concentrate increase the plasma antioxidant capacity in HIV-infected and healthy subjects. DESIGN: Twenty-three HIV-seropositive and 18 seronegative adults were randomized to ingest either 1 l of fruit juice or 30 ml fruit-vegetable-concentrate per day over 16 weeks in addition to their normal Western diet. METHODS: Plasma antioxidant capacity was determined as Trolox equivalent antioxidant capacity (TEAC) at baseline, after 1 and 16 weeks of intervention, and after a 6 week washout. RESULTS: There was no difference in plasma antioxidant capacity between HIV-infected and healthy subjects at baseline (P=0.1). After 16 weeks of intervention TEAC increased in HIV-positive subjects with both types of polyphenol supplementation (juice, 1.38+/-0.07 to 1.42+/-0.04 mM, P=0.034; concentrate, 1.40+/-0.09 to 1.46+/-0.08 mM, P=0.025). TEAC was not altered by either type of supplementation in HIV-seronegative subjects. CONCLUSION: Plasma antioxidant capacity can be increased by long-term ingestion of polyphenols from fruit juices or fruit-vegetable-concentrate in HIV-seropositive but not in HIV-seronegative subjects. SPONSORSHIP: This study was supported by a grant and Cellagon aurum from HG Berner GmbH, Altenholz, and fruit juices from Eckes Granini GmbH & Co. KG, Nieder-Olm.

Adult↗
PubMed2001

Decrease of elevated N,N-dimethylglycine and N-methylglycine in human immunodeficiency virus infection during short-term highly active antiretroviral therapy.

This study investigates fasting serum levels of methionine and related metabolites, vitamin B6, and folate during highly active antiretroviral therapy in therapy-naive human immunodeficiency virus (HIV)-1-infected outpatients. The research design consisted of before and during therapy measurements with a median treatment period of 100 days (range, 50 to 188) in frozen samples. The subjects included 17 consecutive HIV-1-infected outpatients (15 men and 2 women; 25 to 65-years-old). Controls were 42 healthy individuals (28 men and 14 women; 24- to 82-years-old) without serologic evidence of HIV and/or hepatitis C infection and normal clinical chemistry. Subjects received treatment with the reverse transcriptase inhibitors, azidothymidine (AZT) or stavudine (D4T) plus lamivudine (3TC) and either the protease inhibitors, indinavir (IND), nelfinavir (NELF), ritonavir (RITV), or saquinavir (SAQ) at the standard dosage. Serum concentrations of methionine, total homocysteine (tHcy), cystathionine (CYSTA), N,N-dimethylglycine (DMG), N-methylglycine (MG), methylmalonic acid (MMA), and total cysteine, as well as vitamin B6, folate, and soluble tumor necrosis factor receptor p75 were taken at baseline and during highly active antiretroviral therapy. Baseline, serum tHcy, MMA, CYSTA, vitamin B6 concentrations were not significantly different from healthy controls. There was, however, a trend towards lower folate serum concentrations at baseline in HIV-infected patients as compared with healthy controls (P =.06). There were no significant correlations between tHcy and vitamin B6, folate, or MMA. Elevated baseline levels of DMG and MG decreased significantly during antiretroviral therapy (P =.0019 and.04, respectively), whereas no significant changes in serum concentrations of CYSTA, MMA, or methionine were detected. tHcy increased in 12 of 17 patients (P =.09). HIV-infected patients displayed significant alterations (elevated DMG and MG serum concentrations) in metabolite levels of the betaine pathway in methionine metabolism, which might be positively influenced by newly initiated antiretroviral combination therapy.

Adult↗
PubMed2001

Troglitazone and rosiglitazone inhibit the low density lipoprotein-induced vascular smooth muscle cell growth.

Troglitazone (TRO) and rosiglitazone (RSG) belong to the thiazolidinedione class (insulin-sensitizing agents) and exert many of their metabolic effects as peroxisome proliferator-activated receptor gamma (PPARgamma) ligands. In the present study we examined the effects of TRO and RSG on LDL-induced VSMC growth. Pretreatment of VSMC with 1 microM TRO or 0.1 microM RSG completely blocked the LDL-induced cell proliferation as measured by [3H]thymidine incorporation into DNA and by determination of the cell number. We then examined with Western blotting whether these growth suppressing effects are mediated through the mitogen-activated protein kinase (MAPK) pathway, a common signaling pathway activated by growth factors. TRO and RSG had no effect on the LDL-induced stimulation of the MAP kinases ERK1/2, p38 and SAP/JNK. We conclude that thiazolidinediones are potent inhibitors of LDL-induced VSMC growth acting downstream of the cytoplasmic activation of MAPK.

Animals↗
PubMed2001

Controlled balloon inflation reduces long-term restenosis after percutaneous transluminal coronary angioplasty.

PURPOSE: The trauma induced by balloon angioplasty has an impact on the outcome of coronary interventions, such as stent procedures. However, balloon inflation for PTCA is not yet standardized even though procedural and long-term outcomes might be affected. METHODS: During routine PTCA, a total of 454 patients [mean age, 60.9 +/- 9.0 years; 162 (35.7%) with 1-vessel disease; 159 (35%) with 2-vessel disease; 133 (29.3%) with 3-vessel disease] were allotted to computer-assisted dilatation (CAPS) with a pressure slope of 0.2 bar/s (CAPS 0.2; n = 149 patients), 1.0 bar/s (CAPS 1.0; n = 154 patients) or to standard inflation with a hand-driven pump (n = 151 patients). Angiographic follow-up rates after 4.1 +/- 3.2 months were 88.1% for the hand-driven pump, 94% for CAPS 0.2 and 87.7% for CAPS 1.0. RESULTS: Flow reducing (1.3-2.0%) and non-flow reducing (12.6-14.9%) dissections were equally distributed among all groups as were major adverse cardiac events (2.6-4.0%). The stent rate was 1.3% with the hand-driven pump, 0.7% with CAPS 0.2 and 1.3% with CAPS 1.0. Angiographic restenosis rate was 48.9% with the hand-driven pump, 44.3% with CAPS 0.2 and 32.6% with CAPS 1.0. (hand-driven pump versus CAPS 1.0, p < 0.007; CAPS 0.2 versus CAPS 1.0, p < 0.049). CONCLUSIONS: The pressure slope during balloon inflation in PTCA has a significant impact on restenosis. The impact on stent procedures has yet to be determined.

Adult↗
PubMed2000

Short-term stimulation of vascular smooth muscle cells with platelet-derived growth factor (PDGF)-BB and angiotensin II induces.

Growth factors such as the platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II) have been shown to induce vascular smooth muscle cell (VSMC) proliferation after long stimulation periods. Little is known though, about the effects of PDGF-BB and Ang II on VSMC proliferation after short stimulation periods. The purpose of our study was to examine whether a short term (3-60 min) stimulation of VSMC with PDGF-BB or Ang II is sufficient to induce cell proliferation. Incubation of VSMC with Ang II (100 nM) or PDGF-BB (50 ng/ml) caused a significant increase in [3H]thymidine incorporation starting after a 3-min stimulation, while the cell counts required 32 and 8 h of stimulation, respectively. Mitogen-activated protein kinase activation reached a maximum at 5-10 min of PDGF-BB or Ang II stimulation. This study demonstrates that the growth-promoting effects of PDGF-BB and Ang II are strongly dependent on the length of the stimulation period and that while prolonged stimulation periods (>8-32 h) result in VSMC proliferation, short ones (3-60 min) result only in [3H]thymidine incorporation without an increase in cell count, a fact of considerable pathophysiological significance, considering that the time kinetics of growth factors in the VSMC microenvironment have not as yet been clarified.

Angiotensin II↗
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↗