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Biomedical subjects

H Ulrich

Publications and source records attributed to H Ulrich.

At least 37 records · Page 2Linked to original sources

The lipoic acid analogue 1,2-diselenolane-3-pentanoic acid protects human low density lipoprotein against oxidative modification mediated by copper ion.

1,2-Diselenolane-3-pentanoic acid, in which the sulfur atoms of alpha-lipoic acid are replaced with selenium, displayed markedly different antioxidant properties when compared to alpha-lipoic acid. 1,2-Diselenolane-3-pentanoic acid was unable to inhibit protein oxidative modification of human low density lipoprotein (LDL) and bovine serum albumin induced by copper ion or hydroxyl radical, whereas alpha-lipoic acid showed significant protection. However, 1,2-diselenolane-3-pentanoic acid was able to inhibit the formation of lipid peroxidation products in LDL after oxidation by copper, while alpha-lipoic acid did not. Hence the diselenium compound exerts its effects in a lipophilic environment whilst lipoic acid exerts its effects in a hydrophilic environment. These differences in antioxidant activities of the two compounds may be explained, at least in part, by their differing partition coefficients.

Antioxidants↗

Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie.

OBJECTIVE: To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability (HRV). RESEARCH DESIGN AND METHODS: In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coefficient of variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.5 Hz) bands. In addition, cardiovascular autonomic symptoms were assessed. RESULTS: Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA1 levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (-37.6 to 77.1) [median (minimum-maximum)] in the group given ALA and decreased by -0.1 ms (-19.2 to 32.8) in the placebo group (P < 0.05 for ALA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm2 (-0. 09 to 0.62) in ALA, whereas it declined by -0.01 bpm2 (-0.48 to 1.86) in placebo (P < 0.05 for ALA vs. placebo). Furthermore, there was a trend toward a favorable effect of ALA versus placebo for the CV and HF band power spectrum (P = 0.097 and P = 0.094 for ALA vs. placebo). The changes in cardiovascular autonomic symptoms did not differ significantly between the groups during the period studied. No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.

Autonomic Nervous System Diseases↗

Head-activator induced mitosis of NH15-CA2 cells requires calcium influx and hyperpolarization.

In NH15-CA2 cells head activator (HA) stimulates cell proliferation by acting in the G2/M transition. Cells in mitosis were analyzed by flow cytometry 2-4 h after HA application. HA in a dose-dependent manner stimulated mitosis. Mitosis was prevented by preincubation of cells with pertussis toxin identifying the HA receptor as being Gi-protein coupled. As second effect of HA, an increase in intracellular calcium concentration was observed. This increase in calcium concentration was abolished by inhibiting calcium influx from the extracellular space into NH15-CA2 cells either by chelating extracellular calcium with EGTA or by blocking calcium channels. The increase in intracellular calcium concentration led to an activation of calcium-dependent potassium channels. The higher potassium conductance resulted in hyperpolarization of NH15-CA2 cells. Blocking calcium channels with nickel chloride or potassium channels with tetraethylammonium chloride inhibited the effect of HA on cell proliferation. HA-induced mitosis was inhibited by charybdotoxin and apamin, but not by alpha-dendrotoxin confirming the notion that Ca(2+)-dependent potassium channels are involved in mediating the effect of HA on cell division.

Animals↗

Parenteral use of medium-chain triglycerides: a reappraisal.

Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic superiority.

Animals↗

Dose/response curves of lipoic acid R-and S-forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow.

Micromolar concentrations of lipoic acid racemate added to a working rat heart during hypoxia have been previously found to improve aortic flow during subsequent reoxygenation. Since the R-form represents the naturally occurring form of lipoic acid, and the S-form does not reveal a positive influence on ATP synthesis in isolated mitoplasts, a dose/response curve of both enantiomers has been performed in working rat hearts. After the end of perfusion mitochondria were isolated and further analysed. At a concentration of 0.05-0.1 mumol of the R-enantiomer, aortic flow rises precipitously during reoxygenation, reaching over 70% of normoxic values compared to 50% of the controls. By contrast, with the S-enantiomer a value of about 60% is attained at 1 mumol, only. Accordingly, ATPase activity in mitochondria isolated from rat hearts previously treated with 0.05-0.1 mumol of the R- or S-enantiomer was significantly decreased or increased respectively. Consequently, whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity, measured with diphenylhexatriene, revealed a trend towards increase with the R- and decrease with the S-enantiomer. The total amount of thiol added at 0.1 mumol concentration is consistent with a value of 2 nmol/mg mitochondrial protein. This value has previously been found to be connected with -SH groups which add oligomycin-sensitivity to the ATPase complex. It is suggested that oligomycin-sensitive mitochondrial -SH groups contribute to the overall efficiency of low concentrations of lipoic acid R-enantiomer to enhance aortic flow.

Adenosine Triphosphatases↗

Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency.

alpha-Lipoic acid, an essential cofactor in mitochondrial dehydrogenases, has recently been shown to be a potent antioxidant in vitro, as well as being capable of regenerating vitamin E in vitro. In this study, using a new animal model for rapid vitamin E deficiency in adult animals and a new technique for tissue extraction of oxidized and reduced alpha-lipoic acid, we examined the antioxidant action of alpha-lipoic acid in vivo. Vitamin E-deficient adult hairless mice displayed obvious symptoms of deficiency within five weeks, but if the diet was supplemented with alpha-lipoic acid the animals were completely protected. At five weeks on a vitamin E-deficient diet animals exhibited similar decreases in tissue vitamin E levels, whether supplemented or unsupplemented with alpha-lipoic acid: vitamin E levels in liver, kidney, heart, and skin decreased 70 to 85%; levels in brain decreased only 25%. These data show that there was no effect of alpha-lipoic acid supplementation on vitamin E tissue concentrations, arguing against a role for alpha-lipoic acid in regenerating vitamin E in vivo.

Animals↗

Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in non-obese diabetic mice.

In an animal model of type I diabetes, the non-obese diabetic (NOD) mouse, the influence of the antioxidant lipoic acid (LA) on the development of diabetes was investigated. Acceleration of diabetes development with cyclophosphamide (CY) resulted in 60% diabetic animals with severely infiltrated islets within 1-3 weeks. Daily administration of lipoic acid for 20 or 30 days around cyclophosphamide treatment suppressed the incidence of diabetes to 30% (P < 0.05) and 33%, respectively. Semiquantitative analysis of islet infiltration showed a reduction of severe intraislet infiltration and an increase in the percentage of islets with mild per-insular and periductular infiltrates (from 8.4 to 29.6 and 25.9%, respectively, P < 0.01) after lipoic acid treatment. These results show that the protective effect of lipoic acid on diabetes development correlates with partial suppression of islet inflammation. The anti-inflammatory action of lipoic acid may be due to its ability to scavenge oxygen radicals and to suppress nitric oxide production.

Animals↗

Purification and characterization of the head-activator receptor from a multi-headed mutant of Chlorohydra viridissima.

In hydra the neuropeptide head activator (HA) is responsible for head-specific growth and differentiation processes. The effects of HA are mediated by high and low affinity receptors on hydra cells. In the current study HA receptors from a multi-headed mutant of Chlorohydra viridissima were solubilized from the membrane fraction using 1% Triton X-100 and 2.5 M urea. Scatchard analysis showed that the solubilized receptor had a Kd of 1.55 x 10(-9) M, indicating the low affinity subtype of the HA receptor. The solubilized receptor was purified by DMAE chromatography and subsequent affinity chromatography to homogeneity. SDS-PAGE revealed a single protein band with a molecular mass of 96 +/- 4 kDa. The native receptor eluted during gel filtration as a 113 kDa protein, and focussed with an isoelectric point of 4.8.

Animals↗

An optical three-dimensional technique for topographical descriptions of surgical implants.

The purpose of this study was to develop a noncontacting optical method for the topographical description of surfaces. The method is suitable for all types of surgical implants, including threaded ones. The TopScan 3D system employs a scanning spot and a stationary object at a relatively large working distance to enable proper object alignment, and the depth discrimination property of confocal laser scanning microscopy forms the basis of its surface profiling ability. Scanning is achieved by precision movement of the microscope objective along three orthogonal axes (X, Y, Z). Three-dimensional surface topographical maps are produced by performing a series of parallel XZ scans in Y steps. Eighty seven screw-shaped titanium implants were divided into five groups each with a different surface roughness. The five groups were obtained by varying the size of the blasting particles and by leaving one group 'as-machined'. By using the TopScan 3D approach, we were able to calculate different kinds of surface roughness parameters and to produce visual images from the groups. As expected, the surfaces blasted with large particles showed higher values for the surface parameters than those blasted with smaller particles; the latter had higher values than the 'as-machined' screws.

Bone Screws↗

A perimetric nerve fiber bundle map.

The so-called 'nerve fiber bundle defects' in the visual field are considered as being the functional equivalent of retinal nerve fiber bundle damage. This study examines the course and the position of scotoma borders in 159 visual fields with complete nerve fiber bundle defects using high resolution test point patterns. The scotoma border lines were averaged geometrically. The result is presented in the form of mean vectors. This functional map of nerve fiber lines shows a close correspondence to the anatomical course of the retinal nerve fibers. To make the result suitable for topographical analysis of visual fields, 21 areas ('Perimetric Nerve Fiber Bundles') are defined. Certain arbitrary assumptions were necessary because data were to scanty in some nasal regions. Also, the lines had to be fitted into a rectangular grid to be transferable to standard perimetric patterns. Topographical analysis on the basis of these areas may be useful for the evaluation of visual fields, particularly those of glaucoma.

Glaucoma↗

Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels.

The influence of alpha-lipoic acid (LA, thioctic acid, CAS 62-46-4) on thyroid hormone metabolism and serum lipid-, protein- and glucose levels was investigated. In the first setup of experiments administration of LA together with thyroxine (T4) for 9 days suppressed the T4 induced increase of T3 generation by 56%. This suppression was similar to that affected by 6-propylthiouracil (54%). LA or T4 alone did not affect the cholesterol level, but together they led to a reduction. LA decreased the triglyceride level by 45%; the decrease induced by T4 or LA plus T4 was not significant. Total protein and albumin levels decreased by LA plus T4 treatment when compared to the LA control. The slight increase in glucose level by LA or T4 alone was not observed when they were administered together. In the second setup of experiments the administration of T4 for 22 days increased the serum T3 level 3-fold. When LA was combined with T4 and the treatment continued, the T3 production decreased by 22%. T4 reduced cholesterol level by 30%, and LA plus T4 further reduced it by 47%. The triglycerides were not affected. A moderate decrease in total protein was observed after treatment with T4 plus LA; T4 and LA plus T4 decreased the albumin level. The decrease in serum glucose by T4 recovers by LA treatment. These results demonstrate that LA interferes with the production of T3 from T4 when it is co-administered with T4. The elevated level of T3, after T4 administration, is reduced by treatment with LA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Comparative study of 2 dosage forms of liquid dimethicone for ultrasound premedication].

A double-blind study was carried out to compare the effects of a premedication with 4 x 500 mg dimethylpolysiloxane (DPS)/24 hours and with 2 x 500 mg/12 hours before abdominal ultrasonography. The investigations covered 13 abdominal regions in specified planes. The incidence of the unobscured presentation of the selected organs and organ sections per patient served as a basis for a sonography index. This index was 67%, without significant difference between the two groups. We believe that the optimal conditions for sonography are given when the patient is fasting and two 500 mg doses of DPS are administered, one in the evening before and one in the morning at the day of investigation.

Abdomen, Acute↗

Thioctic acid induces dose-dependent sprouting of neurites in cultured rat neuroblastoma cells.

Quantitative computer-assisted evaluation of thioctic acid-induced sprouting in Neuro-2a cells reveals a clear dose dependence with respect to several parameters of sprouting. At first predominantly the length of main sprouts per cell (neurites from cell soma to first branching) and the number of branchings per cell are increased. With the higher dosages, the length of branches per cell rises considerably, too. In contrast, the degree of branching (mean length of neurites per branching) seems to be independent of the concentration of thioctic acid. The capacity of thioctic acid to induce sprouting is discussed in terms of the involvement of SH groups and with regard to regeneration phenomena as they may occur in diabetogenic neuropathy.

Animals↗

The visual field in advanced glaucoma.

For analysis of the morphology of the visual field in advanced glaucoma, we tested 62 eyes of 54 late stage glaucoma patients using program 10-2 on the Humphrey Field Analyzer. The fields, which were already reduced to a small central isle, had mostly typical, asymmetric borders with their largest extend to the temporal lower quadrant and their smallest extend to the upper nasal quadrant. An upper nasal step was very frequent. The boundaries are equivalent to the retinal nerve fiber lines. Actually, the glaucomatous isle is a 'centro-coecal isle', representing a remnant of intact maculo-papillary nerve fiber bundles. A test with a 2 degrees spacing like the Humphrey program 10-2 proved to be useful for routine perimetry in these cases.

Adolescent↗

[Premedication for abdominal sonography--comparison of the efficacy of 2 dimethicone preparations].

Two commercially available preparations of dimethycon with different galenic properties (Paractol flüssig, Sab simplex) were tested for their usefulness as a premedication for abdominal sonography. According to the recommendations of the manufacturers each of 20 patients was pretreated with four different galenic preparations of the two substances that were administered in a randomly assigned sequence. 13 abdominal regions of interest were investigated for visualisation of organs and gas interposition. Both groups of drugs clearly improved the quality of imaging of the abdominal vessels and the epigastric structures, but Paractol proved to have significantly better effects. This is possibly due to a higher dosage of dimethycon in Paractol.

Abdomen↗

Citrulline synthesis--a tool for investigation of the mitochondrial energy metabolism.

The conditions under which citrulline synthesis can be used to stimulate mitochondrial energy metabolism were investigated in isolated rat liver mitochondria. At 25 degrees C, with glutamate as substrate, a lag phase of citrulline formation was observed, which was neither detectable in the presence of succinate nor at 38 degrees C with both substrates. After a high-protein diet, a stationary synthesis was seen from the beginning of incubation for both substrates at either temperature. The high-protein diet was applied to reach maximal citrulline synthesis. Citrulline production was found to be enhanced twice to three times as early as after one to two days. Citrulline formation and associated oxygen uptake vs. temperature were checked in the range from 10 degrees C to 42 degrees C. A linear relationship was noted between temperature and reaction rates in the Arrhenius plot, and the share of citrulline synthesis in the total energy transformation increased with rising temperature. Citrulline synthesis was adopted in experiments to determine the equilibrium state of the adenine nucleotide translocator at 38 degrees C. Just as at 25 degrees C, the translocator operated under disequilibrium conditions at body temperature, too, and the loss of free energy was--3.2 kJ X mol-1.

Animals↗