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D O Stichtenoth

Publications and source records attributed to D O Stichtenoth.

At least 19 recordsLinked to original sources
PubMed2006

Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease.

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58+/-8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), alpha-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 micromol/L; P<0.001) and significantly increased TEAC values (+39.3 microM; P<0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P=0.001) and placebo (-9.2U/L; P<0.001). At baseline, significant correlations were found only between ADMA and SDMA (r=0.281; P=0.002), L-arginine/ADMA and SDMA (r=-0.294; P<0.001), L-arginine/ADMA and oxLDL (r=-0.281; P=0.016), and L-arginine/ADMA and age (r=-0.231; P=0.010). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk.

Adult↗
PubMed2006

Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.

BACKGROUND: According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes. METHODS: A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day. RESULTS: The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed. CONCLUSIONS: The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.

Aged↗
PubMed2004

The second generation of COX-2 inhibitors: clinical pharmacological point of view.

Valdecoxib, parecoxib, etoricoxib and lumiracoxib represent the second generation of selective COX-2 inhibitors. In comparison to the first generation, they show an at least equivalent efficacy in the treatment of pain and inflammation. However, the postulated gain of safety is yet difficult to determine and seems to be, if any, small.

Arthritis↗
PubMed2002

Knowledge on drug dosages of ward physicians.

OBJECTIVE: Dosing errors are a common source for preventable adverse drug events. This study evaluated the knowledge of German hospital physicians with respect to the daily dosage of frequently used drugs. METHODS: A questionnaire survey was carried out among 168 ward physicians from three university and four municipal hospital departments of internal medicine asking for the daily dosage of 17 frequently used drugs. RESULTS: One hundred twenty-seven of 168 physicians returned a completed questionnaire, a response rate of 75.6%. Only 50% of the dose estimates were within the therapeutic range. Even in cases of frequent prescription 7% of the stated doses were overdosed and 15% were underdosed. CONCLUSIONS: The results of this survey suggest that adverse drug events and the lack of therapeutic effect due to dosing errors could be prevented by an improved knowledge of daily dosages.

Clinical Competence↗
PubMed2002

Comparison of different activity parameters in atopic dermatitis: correlation with clinical scores.

BACKGROUND: Several laboratory markers have been described to correlate positively with disease activity of atopic dermatitis (AD). These include soluble adhesion molecules and eosinophil granular proteins. Although the correlation of these parameters with the severity and extent of skin involvement has been repeatedly studied in the past, no systematic investigation has been performed over a lengthy period of time. In addition, no subjective disease parameters recorded by the patient have been included in studies dealing with disease activity. OBJECTIVES: To assess the validity of different objective and subjective parameters [soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), eosinophil cationic protein (ECP), urinary nitrate excretion (reflecting endogenous nitric oxide formation) and the patients' impressions of pruritus, sleeplessness and skin status] as markers of AD disease activity. METHODS: Twenty patients were examined for 1 year and their skin status was evaluated by an established score (SCORAD). sE-selectin, sVCAM-1 and ECP were analysed by commercial test kits. Urinary nitrate concentration was measured by gas chromatography-mass spectrometry. The subjective parameters, pruritus, sleeplessness and impression of skin status, were recorded by the patients on a visual analogue scale. RESULTS: In this long-term trial, only sE-selectin and the subjective parameters showed a statistically significant correlation with the SCORAD score. CONCLUSIONS: Our data indicate that basic clinical scoring remains a most effective and relevant method of recording skin disease activity in AD.

Adolescent↗
PubMed2002

Elevated nitric oxide levels in patients with chronic liver disease and cirrhosis correlate with disease stage and parameters of hyperdynamic circulation.

Chronic liver diseases are accompanied by changes in splanchnic and systemic circulation. These changes are characterised by a reduction in peripheral vascular resistance and an increased cardiac output at rest. An increased release of nitric oxide (NO) has been proposed to play a role in the pathogenesis of vasodilatation and vascular hypocontractility. This study was designed to determine the nitric oxide metabolism measured as circulating nitrate levels in serum/urine in patients with chronic liver disease and cirrhosis. The nitrate concentrations were significantly increased in advanced degrees in cirrhosis Child B and C, and normal or even reduced in patients with chronic active hepatitis and early cirrhosis. In our study the connections between the extent of portal hypertension and nitrate levels were evident. The presence of ascites as well as the the progression of oesophageal varices were associated with higher circulating nitrate levels. The connection between increased nitric oxide production and the haemodynamic sequelae of portal hypertension is also apparent in the significant correlation between plasma renin and serum nitrate levels. Circulating nitrate levels also correlated to the serum interleukin-6 levels. This study demonstrated that the increased nitric oxide metabolism is associated with the haemodynamic alterations induced by portal hypertension.

Ascites↗
PubMed2001

Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells.

The selective induction of PGE(2) synthesis in inflammation suggests that a PGE synthase may be linked to an inducible pathway for PG synthesis. We examined the expression of the recently cloned inducible microsomal PGE synthase (mPGES) in synoviocytes from patients with rheumatoid arthritis, its modulation by cytokines and dexamethasone, and its linkage to the inducible cyclooxygenase-2. Northern blot analysis showed that IL-1beta or TNF-alpha treatment induces mPGES mRNA from very low levels at baseline to maximum levels at 24 h. IL-1beta-induced mPGES mRNA was inhibited by dexamethasone in a dose-dependent fashion. Western blot analysis demonstrated that mPGES protein was induced by IL-1beta, and maximum expression was sustained for up to 72 h. There was a coordinated up-regulation of cyclooxygenase-2 protein, although peak expression was earlier. Differential Western blot analysis of the microsomal and the cytosolic fractions revealed that the induced expression of mPGES protein was limited to the microsomal fraction. The detected mPGES protein was catalytically functional as indicated by a 3-fold increase of PGES activity in synoviocytes following treatment with IL-1beta; this increased synthase activity was limited to the microsomal fraction. In summary, these data demonstrate an induction of mPGES in rheumatoid synoviocytes by proinflammatory cytokines. This novel pathway may be a target for therapeutic intervention for patients with arthritis.

Arthritis, Rheumatoid↗
PubMed2001

S-Transnitrosylation of albumin in human plasma and blood in vitro and in vivo in the rat.

S-Nitrosoalbumin (SNOALB) is the most abundant physiological circulating nitric oxide (NO) carrier regulating NO-dependent biological actions in humans. The mechanisms of its formation and biological actions are still incompletely understood. Nitrosation by authentic NO and S-transnitrosylation of the single sulfhydryl group located at Cys-34 of human albumin by the physiological S-nitroso compounds S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO) are two possible mechanisms. On a quantitative basis, we investigated by gas chromatography-mass spectrometry the contribution of these two mechanisms to SNOALB formation in human plasma and blood in vitro. GSNO and SNOC (0-100 microM) rapidly and efficiently (recovery=35%) S-transnitrosylated albumin to form SNOALB. NO (100 microM) S-nitrosated albumin to SNOALB at a considerably lower extent (recovery=5%). The putative NO-donating drugs glyceryl trinitrate and sodium nitroprusside (each 100 microM) failed completely in S-nitrosating albumin. Bubbling NO into human plasma and blood resulted in formation of SNOALB that inhibited ADP-induced platelet aggregation. Infusion of GS(15)NO in the rat resulted in formation of S(15)NOALB, [(15)N]nitrate and [(15)N]nitrite. Our results suggest that S-transnitrosylation of albumin by SNOC and GSNO could be a more favored mechanism for the formation of SNOALB in the circulation in vivo than S-nitrosation of albumin by NO itself.

Adenosine Diphosphate↗
PubMed2001

Blood donors on medication. Are deferral periods necessary?

OBJECTIVES: Drugs and their metabolites in transfused blood components may cause effects in the recipient. If the treated disorder is not to be regarded as an exclusion criterion from blood donation, donors on medication should be deferred for a period consistent with the drug's pharmacokinetics. GENERAL PRINCIPLES AND METHODS: Peak plasma drug concentrations of 3% or less of the therapeutic concentration were regarded to be safe for the recipient of a blood product. For teratogenic drugs a much lower safety level of less than 0.000001% has been proposed. For the calculation of deferral periods, both the type of blood component to be prepared and the drug's pharmacokinetics for a given formulation were considered. SUGGESTED WAITING PERIODS: For drugs with known teratogenic risks, we suggest a deferral period of 28 plasma-elimination half-lives. For non-teratogenic drugs, a simple, conservative approach could be based on waiting for five plasma-elimination half-lives, thus reaching the required 3% safety level already in any donor. If, however, the type of blood component to be prepared is also considered, a more differentiated approach appears to be appropriate: for blood components containing 50 ml or less plasma from a single donor, donor medication may be disregarded because of the high dilution in the recipient's plasma volume, whereas for blood components with higher plasma contents (250 ml on average) from a single donor on medication the 3% safety level will be achieved by observing the deferral period of five plasma-elimination half-lives mentioned. A guideline for 191 drugs and drug classes has been elaborated accordingly.

Abnormalities, Drug-Induced↗
PubMed2001

Drug expenditure in hospitals: what do German ward physicians know?

AIMS: Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS: A questionnaire survey was carried out among 168 ward physicians from university and municipal hospital departments of internal medicine. RESULTS: One hundred and twenty-seven physicians returned a completed questionnaire, a response rate of 75.6%. On average the physicians successfully identified both low cost and expensive drugs. The prices of inexpensive and moderately expensive drugs were generally overestimated whereas those for the expensive and highly expensive drugs were underestimated in 35% and 68% of respondents, respectively. CONCLUSIONS: The results of this survey of German hospital physicians suggest that a more economically efficient use of drugs could be achieved by an improved knowledge of daily therapeutic costs.

Drug Costs↗
PubMed2001

Effects of intravenous oxygen on prostacyclin and thromboxane formation in patients with peripheral occlusive arterial disease.

Oxygen infusion is used in complementary medicine for treatment of peripheral occlusive arterial disease. The mechanism of action is unknown. Thus, we determined the effects of oxygen infusion on prostacyclin, thromboxane and nitric oxide synthesis. Twelve patients with peripheral occlusive arterial disease received oxygen 40 ml/d intravenously for 3 weeks. Study parameters, analyzed by gas chromatography-mass spectrometry on day 1, 3, 10, 16, 21: 2,3-dinor-6-oxo-PGF(1alpha), colour invisible 2,3-dinor-TXB2 and nitrate in one-hour-urine before and after oxygen infusion, reflecting prostacyclin, thromboxane and nitric oxide synthesis. Urinary 8-iso-PGF2alpha, indicating oxidative stress, was assessed in one patient. Urinary 2,3-dinor-6-oxo-PGF1alpha rose from baseline more than 4-fold after oxygen infusion. In contrast, urinary 2,3-dinor-TXB2 excretion remained unchanged. Oxygen infusion had no effect on urinary nitrate excretion. Urinary 8-iso-PGF(2alpha) was not influenced by oxygen infusion with and without diclofenac pretreatment. Our data demonstrate a shift of the prostacyclin/thromboxane ratio toward prostacyclin by oxygen infusion. Thus, a mechanism of action is provided and clinical trials with intravenous oxygen find a rational basis.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

COX-2 and the kidneys.

The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prosta noid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAID-typical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in "physiologic" constitutive COX-1 and "inflammatory" inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephro genesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.

Animals↗
PubMed1999

Measurement of S-nitrosoalbumin by gas chromatography-mass spectrometry. II. Quantitative determination of S-nitrosoalbumin in human plasma using S-[15N]nitrosoalbumin as internal standard.

A gas chromatographic-mass spectrometric method for the quantitative determination of S-nitrosoalbumin (SNALB) in human plasma is described. The method is based on selective extraction of SNALB and its 15N-labeled SNALB analog (S15NALB) used as internal standard on HiTrapBlue Sepharose affinity columns, Hg2+ -catalysed conversion of the S-nitroso groups to nitrite and [15N]nitrite, respectively, followed by their derivatization to the pentafluorobenzyl derivatives and quantification by GC-MS. Mean recovery of SNALB and S15NALB from plasma was 45%. Mean precision and accuracy within the range 0-10 microM was 95% and 99%, respectively. The limit of quantitation was determined as 100 nM at a precision of 93.8% and an accuracy of 94.8%. Considerable improvement of method sensitivity is possible by eliminating nitrite present in the elution buffer. The limit of detection was 0.2 nM corresponding to 67 amol of S15NALB. In 0.4-ml aliquots of plasma samples from healthy humans, endogenous SNALB was determined at concentrations of 181+/-150 nM (mean +/- SD, n = 23). External addition of SNALB to these plasma samples at 2 microM and 5 microM serving as quality control samples resulted in quantitative recovery of SNALB. Our results show that SNALB occurs in human plasma at concentrations at least one-order of magnitude smaller than those reported in the literature from measurements using chemiluminescence.

Calibration↗
PubMed1998

[New non-steroidal anti-rheumatic drugs: selective inhibitors of inducible cyclooxygenase].

UNLABELLED: MODE OF ACTION OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: Non-steroidal anti-inflammatory drugs (NSAID) exert their major therapeutic and adverse effects by inhibition of prostanoid synthesis. Also the interactions with antihypertensive drugs and lithium are caused by this mechanism of action. Cyclooxygenation is a key enzymatic step in the synthesis of prostanoids. 1990 2 isoforms of the enzyme cyclooxygenase have been identified: Prostanoids synthesized by the constitutive cyclooxygenase (COX-1) are involved in physiological homeostasis. In contrast, the inducible cyclooxygenase (COX-2) produces large amounts of prostanoids, mainly contributing to the pathophysiological process of inflammation. COX-2 SELECTIVE NSAID: The discovery of the cyclooxgenase-isoenzymes ushered in a new generation of NSAID: A drug with selectivity for COX-2 would inhibit proinflammatory prostanoid synthesis while sparing physiologic prostanoid synthesis. Thus, a selective COX-2 inhibitor should be anti-inflammatory with less or no gastrointestinal or other NSAID-typical adverse effects. The experiences with currently used NSAID, which show an increasing incidence of side effects as COX-1 inhibition increases, and studies with the COX-2 selective NSAID salsalate and meloxicam, which have less adverse effects than nonselective COX inhibitors in equivalent antiphlogistic dosage, prove the concept of selective COX-2 inhibition to avoid the NSAID typical side effects. Newly developed drugs with a very high selectivity for COX-2 are now tested in clinical trials. CONCLUSION: So far the results suggest, that selective and highly selective COX-2 inhibitors have significantly fewer gastrointestinal and renal adverse effects and do not inhibit platelet aggregation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Analysis of cysteine and N-acetylcysteine in human plasma by high-performance liquid chromatography at the basal state and after oral administration of N-acetylcysteine.

A high-performance liquid chromatographic method for the determination of free reduced cysteine and N-acetylcysteine in human plasma at the basal state and after oral administration of N-acetylcysteine is described. The method is based on acid-catalysed conversion of plasma thiols to the corresponding S-nitroso derivatives by excess of nitrite and their subsequent cation-pairing RP-HPLC with detection at 333 nm. Recovery rates of cysteine and N-acetylcysteine added to human plasma were 94.6 and 99.6%, respectively. Inter- and intra-day precision were below 6%. In healthy humans (n = 5), free reduced cysteine was determined to be (mean+/-S.E.) 10.0+/-0.96 microM. No N-acetylcysteine was detected in plasma of these subjects above the limit of detection (e.g. 170 nM). The method was successfully applied to a pharmacokinetic study on orally administered N-acetylcysteine to healthy volunteers.

Acetylcysteine↗
PubMed1998

Anesthesiology.

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Anti-Inflammatory Agents, Non-Steroidal↗