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Biomedical subjects

E Graf

Publications and source records attributed to E Graf.

At least 19 recordsLinked to original sources

Effects of delayed administration of octreotide in acute experimental pancreatitis.

Multiple therapeutic modalities studied for acute pancreatitis often show a poor correlation between results obtained in experimental studies and results of clinical trials. One of the main reasons for this discrepancy is that in most experimental studies the drugs were administered immediately after induction of pancreatitis, whereas in the clinical setting there is almost always a delay between the onset of the disease and initiation of the treatment. We studied the effects of a delayed treatment with octreotide, the synthetic analogue of the hormone somatostatin, on acute experimental pancreatitis in rats. The disease was induced by intraparenchymal injections of 0.5 ml 5% sodium taurocholate, and octreotide (10 mg/kg/day s.c.) was started either 4 or 12 hr later. Subcutaneous saline injections were used in controls. One-half of the animals of each study group was sacrificed after 36 hr, and the following parameters were examined: pancreatic weight, plasma pH, serum calcium and amylase, and histopathological damage. The same parameters, as well as survival, were assessed after 20 days in the remaining rats. Neither intrapancreatic saline injections, nor octreotide administration without the induction of pancreatitis, caused any biochemical or histological alterations. Hypocalcemia and acidosis in pancreatitis-induced rats were improved by octreotide, but, as expected, it had no effect on amylase levels. Octreotide ameliorated pancreatic edema, intestinal dilatation, and the histopathological injury score 36 hr after induction of pancreatitis. Mortality was 40% in control animals, and only 20% in rats treated with octreotide. Overall, octreotide had beneficial effects in acute experimental pancreatitis, and was more effective when started earlier. These results indicate that octreotide may have a role in the management of acute pancreatitis.

Acute Disease

Suppression of colonic cancer by dietary phytic acid.

Large differences exist between human populations in the frequency of colonic cancer. Epidemiological evidence indicates that these differences are strongly influenced by country of residence, and a negative correlation has been found between the fiber content of the diet and frequency of colonic cancer. This has prompted the hypothesis that high-fiber diets are in some way protective. However, reanalysis of the dietary data provides equally strong support for the hypothesis that the protective element may be phytic acid (inositol hexaphosphate). This heat- and acid-stable substance is present in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid forms chelates with various metals and suppresses damaging iron-catalyzed redox reactions. Inasmuch as colonic bacteria have been shown to produce oxygen radicals in appreciable amounts, dietary phytic acid might suppress oxidant damage to intestinal epithelium and neighboring cells. Indeed, rapidly accumulating data from animal models indicate that dietary supplementation with phytic acid may provide substantial protection against experimentally induced colonic cancer. Should further investigations yield additional support for this hypothesis, purposeful amplification of dietary phytic acid content would represent a simple method for reducing the risk of colonic carcinogenesis.

Colonic Neoplasms

Antioxidant potential of ferulic acid.

Ferulic acid is a ubiquitous plant constituent that arises from the metabolism of phenylalanine and tyrosine. It occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical which accounts for its potent antioxidant potential. UV absorption by ferulic acid catalyzes stable phenoxy radical formation and thereby potentiates its ability to terminate free radical chain reactions. By virtue of effectively scavenging deleterious radicals and suppressing radiation-induced oxidative reactions, ferulic acid may serve an important antioxidant function in preserving physiological integrity of cells exposed to both air and impinging UV radiation. Similar photoprotection is afforded to skin by ferulic acid dissolved in cosmetic lotions. Its addition to foods inhibits lipid peroxidation and subsequent oxidative spoilage. By the same mechanism ferulic acid may protect against various inflammatory diseases. A number of other industrial applications are based on the antioxidant potential of ferulic acid.

Animals

Prevalence of diabetes mellitus in Ethiopian immigrants.

The prevalence of diabetes mellitus among 445 new immigrant Ethiopian Jews was studied immediately after their arrival to Israel, and found to be 0.4%. This low prevalence could be attributed to their long trek accompanied by severe malnutrition which caused death to the old, weak and sick, leaving a selectively young and healthy population group.

Adolescent

Antioxidant functions of phytic acid.

Phytic acid is a natural plant antioxidant constituting 1-5% of most cereals, nuts, legumes, oil seeds, pollen and spores. By virtue of forming a unique iron chelate it suppresses iron-catalyzed oxidative reactions and may serve a potent antioxidant function in the preservation of seeds. By the same mechanism dietary phytic acid may lower the incidence of colonic cancer and protect against other inflammatory bowel diseases. Its addition to foods inhibits lipid peroxidation and concomitant oxidative spoilage, such as discoloration, putrefaction, and syneresis. A multitude of other industrial applications are based on the antioxidant function of phytic acid.

Animals

Methodology for a better evaluation of the relation between mechanical strength of solids and polymorphic form.

In order to evaluate the role played by polymorphism in the mechanical strength of solid dosage forms (e.g. compressed tablets) and minimize the influence of other factors (such as compaction force, porosity, particle size, and possibly crystal habit), a melted disc technology was developed. With this technique, tablet-shaped discs of zero porosity were prepared by melting powder and subsequent crystallization in the desired modifications. Taking phenobarbitone as a model drug, different methods were used to get discs of forms I, II and III and the amorphous form. Mechanical properties of the discs were assessed, primarily through their bending strength. The Vickers hardness number was also determined for some specimen discs and monocrystals. Results showed that the amorphous form and form III of phenobarbitone gave the toughest discs and would therefore the most suitable materials to manufacture coherent tablets. Moreover, the various preparation methods used resulted in discs of different internal structures. Both crystal size and crystal habit significantly affected the physical properties of the tested materials.

Chemistry, Pharmaceutical

Antiserotonergic inhibition of calcitonin-induced increase of beta-endorphin, ACTH, and cortisol secretion.

In a previous study we observed that calcitonin increases beta-endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor). Fourteen healthy subjects, aged 30-60 years were investigated. All the subjects received 100 IU Salmon calcitonin Sandoz i.v. at 8 a.m. (time 0). Plasma beta-endorphin, ACTH and cortisol were estimated every 30 min from -30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at -30 min and calcitonin i.v. at time 0. beta-endorphin, ACTH and cortisol levels (Mean +/- SEM) rose significantly after calcitonin (peak value at 30-90 min) from 5.2 +/- 0.7 to 15.1 +/- 2.6 pmol/l; from 43.0 +/- 2.7 to 70.7 +/- 4.1 pg/ml and from 10.6 +/- 1.5 to 19.6 +/- 2.1 micrograms/100 ml respectively (p less than 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time -30 did not alter the response of beta-endorphin, ACTH and cortisol to calcitonin (infused at time 0). Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin. We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.

Adrenocorticotropic Hormone

Rosmarinic acid: a new inhibitor of complement C3-convertase with anti-inflammatory activity.

Rosmarinic acid (RA) is a naturally occurring compound, isolated from Rosmarinus officinalis or Melissa officinalis which inhibits the in vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea pig serum. In further experiments this reduced immunohaemolysis was found to be due to inhibition of the C3-convertase of the classical complement pathway. The threshold concentration for inhibition of C3-convertase was 10(-6) mol/l. RA with an optimal inhibitory concentration between 5 and 10 mumol/l., resulting in about 70% inhibition of haemolysis. However, higher concentrations of RA were less effective at inhibiting C3-convertase. The inhibition may not be specific for C3-convertase, since another serine protease, elastase, was also weakly inhibited by RA in vitro. RA also exhibited inhibitory activity in three in vivo models in which complement activation plays a role. Thus, RA (0.316-3.16 mg/kg i.m.) reduced paw oedema induced by cobra venom factor (CVF) in the rat, and at 1-100 mg/kg p.o. inhibited passive cutaneous anaphylaxis in the rat. In addition, at 10 mg/kg i.m. RA impaired in vivo activation by heat-killed Corynebacterium parvum (i.p.) of mouse macrophages, as measured by the decreased capacity of the activated macrophages to undergo the oxidative burst. RA (0.1-10 mg/kg i.m.) did not inhibit t-butyl hydroperoxide-induced paw oedema in the rat, indicating selectivity for complement-dependent processes.

Animals

Nitrogen-to-protein conversion factors in animal feed and fecal samples.

Nitrogen-to-protein conversion factors were calculated for diets and fecal samples from three animal species fed low- or high-fiber diets. The conversion factors based on protein contents determined by amino acid analyses were calculated from total N (Kjeldahl analyses) and recovered amino acid plus NH3-N (amino acid analyses). Conversion factors based on protein contents determined by a fluorescamine assay for amino acids were also calculated from total Kjeldahl-N. The conversion factors based on Kjeldahl-N averaged 5.3 +/- .7 for the diets and 4.0 +/- .5 for the feces in the six animal and diet comparisons when calculated from anhydrous amino acid formula weights. The greatest deviations from the traditional 6.25 conversion factor occurred in the fecal samples of ruminant animals fed a corn-alfalfa meal diet at a maintenance level of intake. In contrast, conversion factors based on amino acid plus NH3-N were quite stable. These factors averaged 5.7 +/- .1 for feeds and 5.5 +/- .1 for feces when calculated from anhydrous amino acid residue weights.

Amino Acids

Phytic acid. A natural antioxidant.

The catalysis by iron of radical formation and subsequent oxidative damage has been well documented. Although many iron-chelating agents potentiate reactive oxygen formation and lipid peroxidation, phytic acid (abundant in edible legumes, cereals, and seeds) forms an iron chelate which greatly accelerates Fe2+-mediated oxygen reduction yet blocks iron-driven hydroxyl radical generation and suppresses lipid peroxidation. Furthermore, high concentrations of phytic acid prevent browning and putrefaction of various fruits and vegetables by inhibiting polyphenol oxidase. These observations indicate an important antioxidant function for phytate in seeds during dormancy and suggest that phytate may be a substitute for presently employed preservatives, many of which pose potential health hazards.

Adenosine Diphosphate