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Biomedical subjects

B Walther

Publications and source records attributed to B Walther.

At least 19 recordsLinked to original sources
PubMed1992

Aplasia of the retinal vessels combined with optic nerve hypoplasia, neonatal epileptic seizures, and lactic acidosis due to mitochondrial complex I deficiency.

A newborn male with mitochondrial complex I deficiency suffered from neonatal epileptic seizures, which later developed into infantile spasms. The infant was blind due to aplasia of the retinal vessels and hypoplasia of the optic nerve. There was congenital lactic acidosis, which persisted in later life. The boy was microcephalic and retarded. Muscular hypotonia later shifted to spasticity. Succinic acid was increased in urine. We assume that the aplasia of the retinal vessels is due to damage of the retinal ganglion cells caused by the mitochondrial disease in the first 3 to 4 months of pregnancy.

Acidosis, Lactic↗
PubMed1992

Nutrient intake and biochemical markers of nutritional status during long-term follow-up after total and partial gastrectomy.

Dietary intake and biochemical nutritional status was studied in patients who had undergone total gastrectomy (TG, n = 10) or partial gastrectomy (PG, n = 10) several years ago. The dietary intake of energy, macronutrients and micronutrients was very similar in the two groups and was also similar to the intake reported for healthy subjects in Sweden. The concentration of alpha-tocopherol in serum was subnormal in the TG group and that of carotene in both groups of patients, and the values were also significantly lower in the TG group than in the PG group. This was probably due to fat malabsorption, since dietary intake was found to be adequate. The proportions of n-6 and n-3 polyunsaturated fatty acids in serum phosphatidylcholine were not significantly different between the TG and PG groups. Iron deficiency was found in three patients in the TG group. Three patients (two TG, one PG) had elevated serum alkaline phosphatase and one patient (PG) had subnormal cobalamin concentration. For ascorbic acid, folate, calcium, phosphorus, magnesium, zinc, copper and selenium, the serum concentrations were normal or close to normal. Although the stores of some micronutrients seemed smaller after total gastrectomy, no major differences in nutritional status were found between the TG and PG groups. For the demonstration of decreased micronutrient stores during long-term follow-up after gastrectomy, an extended profile of biochemical markers of nutritional status is recommended.

Biomarkers↗
PubMed1991

Nutritional status after total and partial gastrectomy with Roux-en-Y reconstruction.

Dietary intake and nutritional status were studied in two groups of patients after total gastrectomy (n = 10) and after partial gastrectomy (n = 10). All patients were reconstructed with a Roux-en-Y loop. Investigations were carried out 4-17 years after the operation. Eight patients in the group undergoing total gastrectomy and four patients undergoing partial gastrectomy had gastric carcinoma and were without recurrent disease 5-15 years after the operation. A clinical dietician conducted an anthropometric evaluation. All patients underwent an upper gastrointestinal endoscopy, clinical examination, [14C]triolein breath test and a blood chemistry profile. The median weight loss from operation to investigation was 2.1 kg in the partial gastrectomy group and 6.7 kg in the total gastrectomy group (n.s.). After partial gastrectomy three patients had a subnormal body mass index (n.s.). This was not found in the total gastrectomy group. Energy intake was below that recommended in seven patients in the partial gastrectomy group (three of them had a subnormal body mass index) and in two in the total gastrectomy group (n.s.) [14C]triolein breath testing revealed fat malabsorption in three patients after partial gastrectomy and in five patients after total gastrectomy (n.s.).

Adult↗
PubMed1991

Structure-metabolism relationships in the hydrolysis of nicotinate esters by rat liver and brain subcellular fractions.

Rat liver and brain subcellular esterase activities toward nicotinic acid esters were studied, under varying conditions, such as pH, organic solvents, protein concentration, duration of incubation, and substrate concentration. Esterases in each subcellular fraction displayed activities that obey Michaelis-Menten kinetics, although subcellular fractions are heterogeneous. The Km values were of the same magnitude, and the Vmax values were lower in microsomes than in cytosol of the liver. Brain activities normalized to protein concentration, were much lower than liver activities, aromatic nicotinates being the best substrates in both tissues. Myelin and brain mitochondria of nerve-ending and neuroglial origin display esterase activity toward phenyl nicotinate. In contrast to brain esterases, liver esterases appear homogeneous, and esterase activities in both tissues react differently to changes in pH. Qualitative and quantitative structure-metabolism relationships are not suggestive of tissue-specific ester hydrolysis.

Animals↗
PubMed1990

Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline.

Previous work has suggested that cytisine and lobeline are of low potency in producing nicotine-like behavioural effects, despite having some nicotine-like peripheral effects and potently inhibiting the binding of tritiated nicotine to the brain of the rat. Rats were trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement. It was confirmed that cytisine had a nicotine-like discriminative effect, but it was much less potent than nicotine itself. Lobeline failed to produce a nicotine-like discriminative effect, even at doses that greatly reduced overall rates of responding. Neither drug attenuated discriminative responses to nicotine. The concentrations of drugs in plasma and brain were determined by HPLC in rats of the same sex, strain and age as those used in the behavioural experiments. The rank order of the ratios of concentrations in brain to plasma was lobeline greater than nicotine greater than cytisine, which was directly proportional to their lipophilicity determined by reversed-phase HPLC. Based on the concentrations in brain and known affinities for high-affinity nicotine binding sites, in vivo tests should show cytisine to be slightly more potent than nicotine and lobeline to have nicotine effects in the doses used. These predictions were not fulfilled and thus, the behavioural effects of cytisine and lobeline cannot be correlated with their effects at the binding site for tritiated nicotine. Since pharmacokinetic factors do not account for this discrepancy, a pharmacodynamic explanation will be necessary.

Alkaloids↗
PubMed1989

Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion.

Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used.

Acute Disease↗
PubMed1989

Fat malabsorption in patients before and after total gastrectomy, studied by the triolein breath test.

The feasibility of using the triolein breath test to demonstrate fat malabsorption was evaluated in a prospective study of patients before and after total gastrectomy and Roux-en-Y reconstruction. Two of 11 patients had subnormal fat absorption before the operation, but 1 and 6 months after the operation 9 of 11 patients had subnormal fat absorption. Peak expiratory 14CO2 (median (range] at the three investigations was 3.9%/h (2.1-5.9%/h), 2.1%/h (1.4-4.5%/h), and 2.0%/h (1.2-6.0%/h), respectively. Patients who underwent a Nissen fundoplication were used as controls. They had normal fat absorption both before and after operation. Serum amylase was not appreciably affected by total gastrectomy and was similar to control values. In contrast, serum albumin decreased 1 month after gastrectomy and recovered after 6 months. In control patients pre- and post-operative albumin concentrations did not differ and were comparable to preoperative albumin values in the total gastrectomy group. The lowered fat absorption may be explained by duodenal bypass with decreased pancreatic stimulation, and it may in part explain the weight loss in patients operated on with total gastrectomy.

Aged↗
PubMed1989

Reduction of secretion from a small-bowel fistula by somatostatin. Case report.

A 69-year-old man with intra-abdominal abscesses and small-bowel fistula after total gastrectomy received two 12-hour continuous i.v. infusions of somatostatin (250 micrograms/h) with a 24-hour interval. Secretion through the fistula decreased markedly during the infusion, with rebound rise after its discontinuation. The concentration of bilirubin in the secretion, but not that of amylase, also fell during somatostatin infusion.

Abdomen↗
PubMed1988

Characteristics of a proteinase from ovarian fluid of the lumpsucker (Cyclopterus lumpus L.).

1. A proteinase has been isolated from the ovarian fluid of the lumpsucker (Cyclopterus lumpus). 2. The enzyme was purified essentially to homogeneity by a one step purification procedure using anion-exchange chromatography. 3. The mol. wt of the denatured enzyme is approximately 20,000 as judged by SDS-polyacrylamide gel electrophoresis. 4. The enzyme is inhibited by serine-proteinase inhibitors and acts in the manner of a trypsin-type proteinase both with respect to specific peptide substrates and enzyme inhibitors. 5. The lumpsucker proteinase exhibits low general proteolytic activity but acts effectively on the specific chromogenic peptide substrates.

Animals↗
PubMed1988

The effects of pneumatic antishock garments in the treatment of critical abdominal injuries in rats.

Thirty rats were subjected to a standardized critical aortic injury and divided into six groups. In addition to controls, the animals were treated with a pneumatic antishock garment (PASG), massive intravenous or intra-aortic saline infusion, or PASG in combination with either massive intravenous or intra-aortic saline infusion. Twenty-six rats were subjected to a standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG, massive intravenous saline infusion, or PASG in combination with massive intravenous saline infusion. These animals were allowed to bleed for 5 minutes before the treatment was started. The treatment with PASG alone prolonged the median survival time significantly from 7 min in the control group to greater than 120 min in the PASG group in rats with an aortic injury and from 33 to greater than 120 min in rats with a hepatic injury. Intravenous infusion of saline did not prolong the median survival time. Intravenous infusion in combination with PASG did not have any positive effects on median survival time or median mean aortic pressure and failed to prolong the median survival time significantly in rats with a liver injury, as six out of eight animals developed a lethal pulmonary edema.

Abdominal Injuries↗
PubMed1987

Brain mitochondrial cytochrome P-450scc: spectral and catalytic properties.

The cytochrome P-450-dependent cholesterol side chain cleavage system of the brain has been studied using nonsynaptic mitochondria as the source of enzymatic activity. The system has been found to bind cholesterol and 11-deoxycorticosterone, producing type I difference spectra, whereas the binding of pregnenolone induced a reverse type I difference spectrum. Inhibitors of cytochrome P-450-linked monooxygenase activities produced type II spectra. The formation of labeled pregnenolone after incubation of brain mitochondria with [4-14C]cholesterol has been obtained, and this formation was inhibited by glutethimide, a specific inhibitor of cytochrome P-450scc. The functional significance of this enzymatic activity is discussed.

Aminoglutethimide↗
PubMed1987

Ethoxyresorufin O-deethylase activity in rat brain subcellular fractions.

Non-polar, lipid-soluble drugs or xenobiotics are able to cross the blood-brain barrier. The brain cytochrome P-450-dependent monooxygenases may oxidize these molecules to more polar and somewhat hazardous metabolites responsible for neurotoxicity. In order to characterize the cytochrome P-450 dependent aryl hydrocarbon hydroxylase activity in brain subcellular fractions, we used 7-ethoxyresorufin as a substrate, as its O-deethylation reflects specifically the activity of the cytochrome P-450 isoform which metabolizes and is induced by polycyclic aromatic hydrocarbons. The results reported here show that this enzymatic activity occurs in both microsomal and mitochondrial fractions, and that the induction after 3-methylcholanthrene treatment remains limited, thus preventing the formation of high levels of harmful metabolites.

Animals↗
PubMed1987

Effects of fundoplication on the antireflux mechanism.

Forty patients with a diagnosis of gastro-oesophageal reflux disease established by 24-h ambulatory pH monitoring were treated by a short 360 degrees fundoplication. Results of postoperative evaluation at 6 months were compared with those from 50 normal volunteers. The amount of gastro-oesophageal reflux at pH monitoring decreased significantly and was less than the reflux in the normal subjects. The pressure and the intra-abdominal length of the distal oesophageal high-pressure zone increased significantly. The pressure was similar to that in the normal subjects while a significantly longer intra-abdominal part of the high-pressure zone was created. The clinical results of the operation were evaluated in 38 patients by an independent gastro-enterologist, and were considered to be excellent in 22 patients, good in 13, fair in 2 and poor in 1 patient. The antireflux procedure provided good control of the gastro-oesophageal reflux in our patients by restoring the major components of the antireflux mechanism.

Adult↗
PubMed1987

Composition of the refluxed material determines the degree of reflux esophagitis in the dog.

To evaluate the influence of the composition of refluxed material in the pathogenesis of esophagitis, a dog model was used to allow esophageal reflux of gastric secretions, duodenal pancreaticobiliary secretions, and a combination of both. Control dogs had only an esophageal incision. Incompetence of the cardia was established in five other groups by transecting the distal sphincter and creating a hiatal hernia. Two groups received moderate or maximal histamine stimulation of gastric secretion. A gastrojejunostomy, pyloromyotomy, and duodenal closure distal to the papilla were added in the other three groups, creating duodenogastric reflux; two were stimulated with histamine and one had a truncal vagotomy and no histamine. Radiologic, manometric, and pH studies showed that incompetence of the cardia was obtained. The dogs were killed 4 wk postoperatively and evaluated for gross and microscopic evidence of esophagitis. Erosive esophagitis was found only in dogs with reflux of gastric juice following maximal acid stimulation. Microscopic reflux changes in esophageal mucosa were seen in all groups; again, changes were most pronounced in dogs with maximal gastric stimulation. The combination of duodenogastric reflux and moderate gastric stimulation produced more significant alterations in microscopic reflux criteria than did moderate gastric stimulation alone. Our conclusions are as follows: In a dog model of gastroesophageal reflux of various combinations of gastric and duodenal secretory components, erosive esophagitis occurred only with maximal gastric stimulation in the absence of duodenogastric reflux. All reflux combinations, however, produced some degree of microscopic changes, suggesting they could eventually cause gross changes with a lengthened experimental time span.

Animals↗
PubMed1987

The activity of 1-naphthol-UDP-glucuronosyltransferase in the brain.

Cerebral microsomes catalysed efficiently the glucuronidation of 1-naphthol, this formation of glucuronide being activated by treatment with Triton X-100 or digitonin. Activated microsomes from the brain of the rat conjugated 1-naphthol with an apparent Km of 95 microM and a Vmax of 5.47 nmol/hr mg protein at 30 degrees C. Microsomal uridine diphosphate (UDP)-glucuronosyltransferase activity in brain towards 1-naphthol was not significantly induced by pretreatment of animals with 3-methylcholanthrene or phenobarbital. These data suggest that UDP-glucuronosyltransferases in brain are different from the hepatic enzymes with regard to biochemical parameters and in response to inducers of drug metabolism. The hepatic UDP-glucuronosyltransferase deficiency in Gunn rats was also observed in the brain.

Animals↗
PubMed1987

Quantitative measurement of cerebral cytochrome P-450 by second derivative spectrophotometry.

Second order derivative spectrophotometry was used to improve the accuracy and reproducibility of cytochrome P-450 measurements in subcellular fractions obtained from the brain. This method allowed better resolution of the overlapping bands of cytochrome P-450 and other iron proteins, as well as a reduction of the effects of turbidity and non-specific components. Using this method, the cytochrome P-450 content of rat brain mitochondrial and microsomal fractions was measured to be 74.2 +/- 2.3 and 5.9 +/- 0.3 pmol/mg protein, respectively.

Animals↗