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Biomedical subjects

H Holm

Publications and source records attributed to H Holm.

At least 37 records · Page 2Linked to original sources

High and low inhibitor soybean meals affect human duodenal proteinase activity differently: in vivo comparison with bovine serum albumin.

The objective of this study was to investigate the effects of high and low inhibitor soybean meals on the duodenal enzyme activities and on the possible regulatory role of gastrointestinal hormones in the pancreatic response. After an overnight fast, 11 healthy volunteers received an intraduodenal infusion of saline for 60 min. This was followed by infusion of either of three test meals: extract of raw soybeans (RS), a low inhibitor soy protein isolate (SPI) or bovine serum albumin (BSA), 10 g/h for 60 min. Then saline was again given intraduodenally for 30 min. Gastric juice was collected continuously and duodenal juice and peripheral blood samples were collected every 10 min. Duodenal chymotryptic activity was severely inhibited by RS, whereas SPI and BSA increased the chymotryptic activity. Tryptic activity showed a transient reduction (55%) during RS infusion, whereas BSA and in particular SPI increased the tryptic activity. No change was seen in amylase activity. The lack of total inhibition of tryptic activity has been studied further and is the subject of the accompanying paper. The peripheral plasma levels of cholecystokinin (CCK) increased significantly during BSA but not during SPI or RS infusions. Thus, CCK levels were not increased by the inhibition of the proteolytic activity by RS in duodenal juice.

Adult↗

High and low inhibitor soybean meals affect human duodenal proteinase activity differently: in vitro comparison of proteinase inhibition.

The purpose of the study was to investigate the in vitro inhibition of the proteolytic activity in samples of duodenal juice obtained during instillation of raw soybeans in humans. The results suggested the presence of an inhibitor-resistant trypsin. Practically no inhibition was obtained with phenylmethylsulfonyl fluoride, aprotinin, human alpha 1-antitrypsin or lima bean trypsin inhibitor. Specificity against synthetic substrates was different from that obtained in the absence of raw soybeans. Duodenal aspirates containing this new trypsin activity were able to further inhibit tryptic and chymotryptic activity of basal aspirates from the duodenum, demonstrating surplus amounts of inhibitors in the duodenal juice. Further incubation of trypsin-inhibitor complexes at 37 degrees C, in the presence of surplus uninhibited (trypsin and chymotrypsin) duodenal juice, restored tryptic activity. This activity was not inhibitor-resistant. The results obtained for trypsin activity based on esterase assays were confirmed by a proteolytic assay. It is concluded that the increase in tryptic activity in human duodenal juice during raw soybean infusion is due to a previously unidentified inhibitor-resistant trypsin and not due to inactivation of the inhibitors in raw soybeans.

Adult↗

Effect of acute potassium depletion and thiazide treatment on blood glucose in the normal rat.

The effect of potassium depletion and a thiazide diuretic on glucose metabolism was investigated in male rats. Potassium depletion was induced by potassium-deficient diet and ion-exchange resin by stomach tube for 5 days. Plasma and muscle potassium was reduced by 30% (P less than 0.001), and fasting blood glucose concentration was elevated by 20% (P greater than 0.025) by potassium depletion. Hydroflumethiazide 10 mg/kg given orally once daily for 8 days produced no further alteration in any parameter. We conclude that acute potassium depletion in the rat may increase fasting blood glucose concentration, whereas addition of short-term thiazide treatment does not seem to potentiate this effect.

Animals↗

Net protein utilization determined by rat bioassay of a protein hydrolysate and a diet for children with phenylketonuria.

In a previous study (Kindt et al. 1983, 1984) it was assumed that a protein hydrolysate, devoid of phenylalanine, together with intact protein as given to children with phenylketonuria (PKU), was equivalent to egg or milk protein. One group of children was given this 'PKU protein' in amounts corresponding to the Joint FAO/WHO ad hoc Expert Committee (1973) recommendations. The results indicated that the Joint FAO/WHO ad hoc Expert Committee (1973) recommended levels of protein intake were marginal. The purpose of the present study was to evaluate whether the quality of the protein hydrolysate, together with intact protein ('PKU protein'), is equivalent to egg or milk protein. This was done using a rat bioassay. Four protein sources were used: (1) egg protein, (2) protein hydrolysate, (3) protein hydrolysate diluted with non-essential amino acids, (4) protein hydrolysate mixed with food proteins ('PKU protein'), comparable with the diet previously used (Kindt et al. 1983, 1984). The results indicated that the 'PKU protein' was of very high quality: net protein utilization (NPU) greater than 90. The protein hydrolysate alone and the protein hydrolysate diluted with non-essential amino acids gave a NPU greater than 80. The conclusion drawn from the present study is that the 'PKU protein', as used in the treatment of children with PKU, is equivalent to egg or milk protein. This supported the view that the Joint FAO/WHO ad hoc Expert Committee (1973) recommended levels of intake were marginal.

Animals↗

Metabolism of ochratoxin B and its possible effects upon the metabolism and toxicity of ochratoxin A in rats.

A metabolic product was formed from ochratoxin B by rat liver microsomal fractions in the presence of NADPH. It was isolated from the incubation mixture by extraction, thin-layer chromatography, high-pressure liquid chromatography, and crystallization. On the basis of mass and nuclear magnetic resonance spectroscopy, the structure is suggested to be 4-hydroxyochratoxin B. The Km for the formation of 4-hydroxyochratoxin B was determined, and the hydroxylation of ochratoxin A was not altered by the presence of ochratoxin B. Rats were given ochratoxin A or B, or a mixture of both intraperitoneally. The ratios of the three metabolites, ochratoxin A, (4R)-4-hydroxyochratoxin A, and ochratoxin alpha, excreted in the urine did not change in the presence of ochratoxin B. Ochratoxin B was metabolized to 4-hydroxyochratoxin B and ochratoxin beta, but in a different ratio than for the ochratoxin A metabolites. When given intraperitoneally, ochratoxin beta was excreted within 24 h. In rats treated with ochratoxin A alone, the food intake was reduced by 50%, and histologically severe lesions, degeneration, and necrosis were observed in the proximal tubules. When ochratoxin A and B given in combination, the animals were clinically unaffected and histologically there was only slight damage of proximal tubules. These observations indicate that ochratoxin B considerably reduces the toxic effects of ochratoxin A.

Animals↗

Tailoring of the diet for the individual in maple syrup urine disease: long-term home dietary treatment of an adult patient with MSUD by monitoring of daily intake with a personal computer. A case report.

The clinical appearance of maple syrup urine disease (MSUD) is due to reduced activity of the enzyme branched-chain alpha keto acid decarboxylase (alpha-BCKA-decarboxylase), thereby affecting the metabolism of the branched-chain amino acids (BCAA), leucine (Leu), isoleucine (Ile) and valine (Val). The aim of the therapeutic regime in MSUD is to keep the concentration of toxic metabolites within individual tolerance limits. The case of a 46-year-old female patient is reported. Energy expenditure was calculated by recording activities and indirect calorimetry. Nitrogen requirement and tolerance level of BCAA were estimated during parenteral nutrition with stepwise increasing supply of amino acids. A diet was designed within these limits, and a computer program was made to assist the patient in keeping her diet within the estimated limits.

Amino Acids, Branched-Chain↗

Pancreatic proteinases from man, trout, rat, pig, cow, chicken, mink and fox. Enzyme activities and inhibition by soybean and lima bean proteinase inhibitors.

1. The specific activities of the trypsins and chymotrypsins, measured with synthetic substrates, varied within one order of magnitude. 2. The trout trypsin and chymotrypsin were 5-15 times as efficient in hydrolyzing casein as the remaining animals. 3. The inhibition of total caseinolytic activity in extracts of pancreatic tissue by SBTI and inhibitors in crude extracts of raw soybeans varied ten-fold. 4. The animals may be ranked as follows according to the sensitivity of the caseinolytic activity to SBTI; trout greater than fox, chicken, greater than pig greater than rat, cow greater than mink greater than man.

Animals↗

Lack of hyperglycemic effect of chlorothiazide in normal rats fed diets with different carbohydrate content.

The effect of chlorothiazide (CT) on blood glucose and liver glycogen was investigated in rats fed either a standard, a carbohydrate-rich, or a carbohydrate-poor diet. CT did not alter blood glucose concentration or liver glycogen content in rats fed the carbohydrate-rich diet. After 5 days on the carbohydrate-poor diet, an oral glucose load produced significantly smaller rate constant for glucose disappearance from blood and significantly greater area below the glucose concentration--time curve than after a standard diet, but CT did not further alter these parameters. Nor did oral CT for 19 days alter glucose tolerance. In conclusion, CT in single dose or short term studies does not seem to alter glucose metabolism in the normal male rat.

Animals↗

Metabolism of ochratoxin A by rats.

Albino rats were given ochratoxin A (6.6 mg/kg body weight) intraperitoneally or per os. Independent of route administration, 6% of a given dose was excreted as the toxin, 1 to 1.5% as (4R)-4-hydroxyochratoxin A, and 25 to 27% as ochratoxin alpha in the urine. The metabolite (4S)-4-hydroxyochratoxin A, which is formed by rat liver microsomes in the presence of NADPH, was not detected. Only traces of ochratoxins A and alpha were found in feces. Identical experiments were carried out with brown rats, since the Km value for the formation of the 4S epimer was considerably lower when brown rat microsomes were used. About the same ratios of metabolites and metabolite recoveries as those found for albino rats were found for brown rats. Brown rats were also given the two hydroxylated metabolites and ochratoxin alpha (0.66 mg/kg body weight) intraperitoneally. The three compounds were excreted in the urine; within 48 h, 90% recovery of ochratoxin alpha and 54 and 35%, respectively, of the 4R and 4S isomers were observed.

Animals↗

Soybean proteinase inhibitors and human proteolytic enzymes: selective inactivation of inhibitors by treatment with human gastric juice.

The stability of soybean proteinase inhibitors to 0.1 M HCl and to human gastric juice was investigated. Purified Kunitz soybean inhibitor (SBTI), purified Lima bean inhibitor (LBI), and crude, aqueous extract (1:5 w/v) of three varieties of soybeans were incubated for 24 hours at 37 degrees. The SBTI, the LBI, and the soybean extracts were mixed with gastric juice or 0.1 M HCl in amounts corresponding to 4.0 g SBTI, 2.4 g LBI, and 130 g soybean meal per liter. The trypsin and chymotrypsin inhibitor activities of the incubation mixtures were measured after 0.0, 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours of incubation. Human pancreatic juice was used as enzyme source. SBTI was rapidly inactivated by the incubation with gastric juice. LBI was hardly affected by the incubation. The trypsin and chymotrypsin inhibitor activities of the soybean extracts were reduced to 60-70%, indicating that SBTI contributed 1/3 of the inhibitor activity of these varieties. Thus, the compact, rigid inhibitors, such as the Bowman-Birk, were responsible for the remainder. The latter group of inhibitors, when ingested with the soybeans, will not be inactivated by passage through the stomach. They probably reach the duodenum in an active form.

Chymotrypsin↗

Treatment prevalence in psychiatric outpatient care in Finland. A comparative study of two areas.

Psychiatric outpatients are surveyed in two separate areas, one (the city of Turku) with clearly above-average provision of mental-health services and the other (predominantly rural Eastern Satakunta) with services corresponding to the average for the country as a whole. The results show that in Turku 3.25% and in Eastern Satakunta 1.98% of the population aged 15 years or more had visited an outpatient treatment unit during the 4-month observation period. Compared with Eastern Satakunta, the patients in turku were relatively more often young persons, men (nearly as often as women), persons in the higher social classes and patients with psychiatric disorders other then psychosis. Treatment received by the patients in Turku was more intensive and included more psychotherapeutic elements. Particularly family-type and group-type therapies were more common in Turku than in Eastern satakunta. The results are considered from the viewpoint for both epidermiologic research and health care policy.

Adolescent↗