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Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 307 records · Page 17Linked to original sources
PubMed1991

Beneficial effects on serum lipids in noninsulin dependent diabetics by acarbose treatment.

Acarbose (Bay g 5421, Glucobay; CAS 56180-94-0) inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. It is therefore efficient as a first-line drug in the treatment of noninsulin-dependent diabetics (NIDDM) insufficiently treated with diet alone. Information is scarce whether under acarbose treatment the lipid metabolism can also be improved. Therefore the changes of triglycerides, cholesterol and HDL-cholesterol were analyzed in a randomized double-blind placebo-controlled trial. In brief, 94 NIDDM aged 43 to 70, after a pretreatment period of at least 3 months, were treated with 100 mg acarbose t.i.d. or placebo for 24 weeks. The patients were recruited after a 4-week screening phase with reinforcement of diet. The most impressive results of acarbose treatment were lowering of blood glucose and insulin, especially in the postprandial state, and of HbA1 (glycosylated hemoglobin). Results on lipids: The initial serum cholesterol levels showed a broad spectrum. Low concentrations remained unchanged under acarbose, while high concentrations (the upper tercile) decreased from 273 to 251 mg/dl. This effect was statistically significant compared to placebo. HDL-cholesterol levels increased continuously under acarbose and placebo as well thus indicating some study effect. Similarly, fasting triglycerides leveled down under acarbose and placebo. However, drastic differences appeared in postprandial triglycerides which were checked 1 and 5 h after a test meal given at entry and at finish of the study. The lowering by acarbose compared to placebo was highly significant for the 1 h postprandial concentrations. It is concluded that acarbose treatment can reduce elevated cholesterol concentrations and postprandial triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗
PubMed1991

Dietary fish and prostanoid formation in man.

Dietary mackerel causes the increase of timnodonic acid (eicosapentaenoic acid) in all platelet phospholipid classes, at the expense of arachidonic acid. Because of these fatty acid changes, the potency of platelets to produce cyclo oxygenase products from the 2-series is greatly reduced. However, upon mild platelet triggering, changes in TxB2 formation are hardly significant, strongly depend on dietary compliance and require a high fish intake. The reduced formation of 2-series prostanoids is only partly compensated for by the increased formation of timnodonic acid-derived products. Urinary PGI metabolites suggest that dietary fish is associated with the enhanced turnover of PGI3 without a concomitant reduction in PGI2 formation. Since the site of PGI formation is not known, and an effect of dietary fish on the prostanoid metabolic routes cannot be excluded, the physiological relevance of these results is uncertain.

Arachidonic Acid↗
PubMed1991

Tobacco-specific nitrosamines in commercial cigarettes: possibilities for reducing exposure.

Tobacco-specific nitrosamines (TSNA) are powerful carcinogens found in tobacco and tobacco smoke in relatively high concentrations. Tar delivery, which is generally accepted as an index for the carcinogenic potential of cigarette smoke, must be declared in most European countries. In this investigation of more than 170 types of commercial cigarettes from several European countries and the USA, no correlation was observed between tar delivery and mainstream smoke concentration of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). Therefore, although crucial, tar delivery alone is not a sufficient index for the carcinogenic potential of cigarette smoke. It is proposed that TSNA concentrations be determined for characterization of the carcinogenic potential of cigarettes with low and ultra-low tar yields and that these be declared by an additional and adequate parameter. The mainstream smoke concentrations of NNN and NNK are given by the amounts of preformed compounds in tobacco, which is dependent on the nitrate content of the tobacco and the tobacco type. A further important determinant of the exposure of smokers to TSNA is the total volume drawn through a cigarette while smoking, which is dependent on puff volume and puff frequency and which directly influences TSNA transfer. Smokers inhale higher volumes when smoking low-nicotine cigarettes, so that low NNN:nicotine and NNK:nicotine ratios result in decreased exposure to TSNA. Reduction of exposure to TSNA can be achieved by selecting tobaccos with low levels of preformed TSNA (low nitrate content, small amounts of burley tobaccos and stems) and by manufacturing cigarettes with low NNN:nicotine and NNK:nicotine ratios.

Carcinogens↗
PubMed1991

Surrogate motherhood: attachment, attitudes and social support.

In recent years, there has been a revival of interest in the procedure of using a surrogate mother to help infertile couples have a child. One of the issues brought into public awareness by the Baby M case, where the surrogate mother refused to give up the baby to the biological father, has been the nature of the attachment of the surrogate mother to the fetus. Thus far, research has not addressed this issue of attachment as well as it has considered other variables involved in the process of surrogacy. The current exploratory study focuses on differences between two groups of pregnant women - surrogate mothers and nonsurrogate mothers - in the degree and quality of attachment, attitudes toward pregnancy, and social support. An understanding of what pregnancy signifies for surrogate mothers is developed, based on objective measures and informal interviews with surrogate and nonsurrogate mothers. The implications of the various phenomena associated with surrogate motherhood are also considered.

Adult↗
PubMed1990

Subcutaneously applied magnesium protects reliably against quinolinate-induced N-methyl-D-aspartate (NMDA)-mediated neurodegeneration and convulsions in rats: are there therapeutical implications.

Quinolinate (QUIN), an agonist of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, was used to model glutamate-induced primary or secondary brain damage. Rats intracerebroventricularly injected with QUIN (1 mumol in 2 microliters) showed convulsive reactions and heavy neurodegeneration in the hippocampal formation. MgSO4 (1 M solution injected subcutaneously; 0.6 or 0.3 g/kg) was found to protect completely against QUIN neurotoxicity if administered simultaneously or 1 h after exposure to QUIN. Preliminarily, LD50 for MgSO4 was estimated approximately at 1.2 g/kg. The application of magnesium is discussed to be a potentially powerful therapeutic principle in case of brain injury and convulsive disorders.

Animals↗
PubMed1990

The purification and amino acid sequence of the lethal neurotoxin Tx1 from the venom of the Brazilian 'armed' spider Phoneutria nigriventer.

A lethal neurotoxic polypeptide of Mr 8 kDa was purified from the venom of the South American 'armed' or wandering spider Phoneutria nigriventer by centrifugation, gel filtration on Superose 12, and reverse phase FPLC on columns of Pharmacia PepRPC and ProRPC. The purified neurotoxin Tx1 had an LD50 of 0.05 mg/kg in mice following intracerebroventricular injection. The complete amino acid sequence of the neurotoxin was determined by automated Edman degradation of the native and S-carboxymethylated protein in pulsed liquid and dual phase sequencers, and by the manual DABITC/PITC double coupling method applied to fragments obtained after digestions with the S. aureus V8 protease and trypsin. The neurotoxin Tx1 consists of a single chain of 77 amino acid residues, which contains a high proportion of cysteine. The primary structure showed no homology to other identified spider toxins.

Amino Acid Sequence↗
PubMed1990

[Micturition pattern in men 60-70 years of age. A study done on an urban population].

A total of 1,065 men aged 60-70 years replied to a questionnaire about their micturition patterns. At the time of the study, 81 men had already been treated operatively for prostatic hypertrophy and 29 men were submitted to operation at a later date. The remaining 955 men remained untreated until March 1987. Approximately 1/3 of the untreated men accepted the symptoms of pollakisuria, after-drip and weak flow. The men who had been treated previously showed the same frequency of symptoms as the untreated men but the frequency of symptoms was considerably increased in men requiring treatment. After-drip is not a specific symptom of prostatism.

Aged↗
PubMed1990

Intact parathyroid hormone in primary hyperparathyroidism.

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.

Adenoma↗
PubMed1990

Tobacco-specific nitrosamines in Canadian cigarettes.

Twenty-five brands of Canadian commercial cigarettes were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and in mainstream smoke as well as for nitrate in tobacco. Preformed N'-nitrosonor-nicotine (NNN) in the tobacco ranged from 265 ng to 979 ng/cigarette, preformed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranged from 465 ng to 878 ng/cigarette. The mainstream smoke concentration for NNN was between 5 ng and 39 ng/cigarette and for NNK between 5 ng and 97 Ng/cigarette. The nitrate levels were between 0.3 mg and 3.4 mg/cigarette. The NNK levels in tobacco and in mainstream smoke were higher than the NNN levels, which is typical for Virginia-type cigarettes. Based upon the average mainstream smoke concentration of the three most popular Canadian cigarette brands, an average TSNA delivery for 20 cigarettes of 0.7 micrograms NNN and 1.7 micrograms NNK can be calculated, which is less than the average for West German cigarettes. The results of this investigation demonstrate that there seems to be a good correlation between the TSNA and tar deliveries in mainstream smoke. However, no correlation between the level of preformed TSNA in tobacco and the tar delivery in mainstream smoke could be observed. It is demonstrated that the good correlation between the tar and TSNA deliveries in mainstream smoke can only be attributed to the unusual good correlation between the tar delivery and the ventilation ratio. For the cigarettes investigated, which seemed to be Virginia-type cigarettes, with few exceptions, the ventilation ratio had a much higher influence on the mainstream smoke concentration than the level of preformed TSNA in tobacco.

Canada↗
PubMed1990

Influence of dietary fish on eicosanoid metabolism in man.

Two groups of 40 volunteers were given a dietary supplement consisting of 135 g of mackerel or meat (control) paste per day for 6 weeks. Compliance was about 80% in both groups and the daily intake of 20:5(n-3) and 22:6(n-3) from the mackerel supplement was about 1.3 and 2.3 g, respectively. In collagen-activated platelet rich plasma, the potency of blood platelet to produce HHT from arachidonic acid (AA) clearly reduced in the mackerel group, whereas the formation of HHTE from timnodonic acid (TA) increased slightly. Changes in the formation of HHT and HHTE, measured by HPLC, correlated significantly with those of TxB2 and TxB3, respectively, measured by GC/MS. Changes in the formation of the lipoxygenase products HETE (ex AA) and HEPE (ex TA) were qualitatively similar to that seen for the cyclo-oxygenase products, but quantitatively the responses were smaller. Formation of ir TxB2 in clotting blood significantly reduced in the mackerel group. In collagen-activated, citrated whole blood, TxB2 formation tended to be reduced in the mackerel-supplemented volunteers. Mackerel consumption was associated with the formation of considerable amounts of PGI3, as judged from the appearance of 2,3-dinor-delta 17-6-keto-PGF1 alpha in urine. The amount of the major metabolite of PGI2, 2,3-dinor-6-keto-PGF1 alpha was not reduced, or even increased. The daily amount of tetranor prostaglandin metabolites in the urine did not change significantly, which indicates that mackerel supplementation did not alter the formation of prostaglandins E and F.

Arachidonic Acid↗
PubMed1990

Incorporation of a subacute test with zebra fish into a hierarchical system for evaluating the effect of toxicants in the aquatic environment.

Single-species laboratory tests were used to assess the acute toxicity of halogenated phenolic compounds. No single test system was most sensitive to all of the compounds examined, substantial variations in the sensitivity of the various organisms were noted, and there was no correlation between the toxicities assayed with different test systems. The zebra fish (Brachydanio rerio) embryo/larvae system was used to examine subacute effects using two of the compounds, and a protocol was developed with 6 weeks preexposure to the toxicant. Preexposure decreased the lowest observable effect concentration by a factor of about 4, and the effect was completely reversible during a 6-week postexposure period in the absence of the toxicant. An enclosed system for carrying out the zebra fish embryo/larvae test was developed and evaluated with three neutral volatile compounds: the median survival time and the frequency of occurrence of deformation were examined as end points. The effect of pH on toxicity was evaluated in buffered media for four of the test systems: toxicity increased markedly at the lower pH values, and it could be shown that the ionized forms of the phenols were not the only contributors to toxicity. It is proposed that the zebra fish system incorporating preexposure could be incorporated into a hierarchical system using a range of organisms for assessing acute toxicity in single species under laboratory conditions and multicomponent systems simulating natural ecosystems.

Animals↗
PubMed1990

The retarded electrophoretic migration of p56lck induced by vanadate in lymphoma cells correlates with modified kinase activity.

p56lck is a src related lymphocyte specific tyrosine protein kinase which undergoes specific changes during T-cell activation, particularly the appearance of slow migrating forms. To analyze these forms, LSTRA cells were treated with vanadate. This resulted in increased phosphorylation of p56lck with the appearance of slow migrating forms. Renaturation of the p56lck bands after gel migration showed that vanadate mostly increased the activity of the lower band of p56lck. The upper bands had a reduced specific activity. In addition, the upper bands from vanadate treated cells displayed additional phosphorylated sites.

Animals↗
PubMed1990

Investigations on the origin of tobacco-specific nitrosamines in mainstream smoke of cigarettes.

The origin of tobacco-specific nitrosamines (TSNA) in mainstream smoke and the possible contribution of synthesis during the smoking procedure was investigated. Addition of the nitrosamine precursors nitrate and nicotine to the tobacco prior to smoking did not change the mainstream smoke concentrations of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), whereas the mainstream smoke concentration of N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) increased after spiking the cigarettes with nitrate. Data for TSNA in tobacco and in mainstream smoke and for nitrate in tobacco of commercial cigarettes of the West German market, taken from previous investigations, were used to calculate the mainstream smoke/tobacco ratios for NNN and NNK. These ratios were corrected for ventilation and cigarette length. It is shown that the ratios are constant and neither depend on the nicotine level nor on the nitrate level of the tobacco except for NNK in the nitrate rich dark tobacco type cigarettes. For nonfilter cigarettes the transfer rates of NNN and NNK which had been corrected for ventilation and cigarette length amounted to 23 or 34% respectively. For filter cigarettes a transfer rate of 13% for NNN and 23% for NNK was calculated. Furthermore it is shown that the mainstream smoke/tobacco ratios for NNN and NNK are constant over the whole length of the cigarettes except for NNK in dark tobacco type cigarettes. The results of this investigation indicate that pyrosynthesis of NNN does not occur and that it is very unlikely for NNK at least for lower nitrate levels. Thus with few exceptions the TSNA burden of smokers is predominantly influenced by the amount of preformed NNN and NNK in tobacco.

Carcinogens↗
PubMed1990

Catabolism of leukotriene B5 in humans.

Human neutrophils, enriched by dietary supplementation with eicosapentaenoic acid, form leukotriene (LT)B5 in addition to LTB4 upon stimulation. LTB5 is one order of magnitude less biologically active than the potent chemokinetic and chemoattractant LTB4. Catabolites of LTB5 have not yet been characterized in vitro and ex vivo. It is unknown whether catabolism of LTB5 interferes with catabolism of LTB4. This report describes catabolism of LTB5 to 20-OH-LTB5, which in turn is catabolized to 20-COOH-LTB5. The structures of the two catabolites were established by UV-absorbance, behavior on reverse-phase high-performance liquid chromatography, enzymatic analysis of human neutrophils, and gas chromatography-mass spectrometry. In vitro, formation of LTB4 was delayed and formation of its catabolites was depressed by exogenous eicosapentaenoic acid. By supplementing the diet of six volunteers with 5 g eicosapentaenoic acid/day for 7 days, eicosapentaenoic acid quadrupled in neutrophil phospholipid fatty acids. Consequently, LTB5, 20-OH-LTB5, and 20-COOH-LTB5 were detected ex vivo. In contrast to the findings in vitro, however, levels of LTB4, 20-OH-LTB4, and 20-COOH-LTB4 were unaltered by the dietary intervention. Thus, in vitro, but not ex vivo, addition of eicosapentaenoic acid, and subsequent formation of LTB5, impeded catabolism of proinflammatory LTB4.

Chromatography, Gas↗
PubMed1990

Alpha-adrenoceptor mediated facilitation of acetylcholine release in the rat perfused heart.

Rat hearts were isolated with the vagus nerves intact and perfused, and the neuronal acetylcholine stores were pulse labeled with [14C]choline. The overflow of [14C]choline/acetylcholine evoked by extrinsic vagus nerve stimulation (3 Hz and 720 pulses or 10 Hz and 1200 pulses) was determined by liquid scintillation spectrometry and used as a measure for acetylcholine release. The postjunctional changes in atrial contraction and beating frequency were also recorded. Compared to controls, oxymetazoline and xylometazoline [but not clonidine, (3,4-dihydroxyphenyl-amino)-2-imidazoline), methoxamine and norepinephrine] enhanced the evoked overflow of 14C-activity in a concentration-dependent manner without changing the ratio between choline and acetylcholine determined by paper chromatography. Norepinephrine (10 mumol/l) inhibited the evoked overflow in the presence of propranolol plus yohimbine. The oxyme-tazoline-induced increase in evoked overflow was unaffected by rauwolscine (1 mumol/l), idazoxan (0.3 and 5 mumol/l), and yohimbine (0.3 and 5 mumol/l), but significantly reduced by phentolamine (5 mumol/l), prazosin (0.03 mumol/l), the (-)-enantiomer of WB 4101 (0.1 mumol/l) and SK&F 104078 (3 mumol/l). The overflow of 14C-activity evoked by field stimulation was increased by oxymetazoline the absence and presence of hemicholinium-3. The results are compatible with an alpha-1 adrenoceptor-mediated facilitation of exocytotic acetylcholine release from the rat heart in vitro. The increase in evoked neurotransmitter overflow, however, was not accompanied by an increase in postjunctional heart responses to vagus stimulation due to nonselective blocking properties of the facilitating agonists.

Acetylcholine↗