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The antiinflammatory profile of (5H-dibenzo[a,d]-cyclohepten-5-ylidene)acetic acid (WY-41,770), an agent possessing weak prostaglandin synthetase inhibitory activity that is devoid of gastric side effects.

Wy-41,770 [(5H-dibenzo[a,d]cyclohepten-5-ylidene)acetic acid], a novel acrylic acid, was compared to indomethacin and aspirin in standard antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory, analgesic and antipyretic activity of Wy-41,770 (oral ED50S 50-170 mg/kg) was similar to aspirin; however, it was considerably more potent orally in adjuvant arthritis in the rat (ED50, 16 mg/kg) and urate-induced synovitis in the dog (ED50, 4.5 mg/kg). Wy-41,770 was a weak inhibitor of prostaglandin biosynthesis and did not inhibit either 5- or 15-lipoxygenase. Furthermore, the cellular migration characteristic of carrageenan pleurisy was not affected by Wy-41,770. Unlike a majority of NSAIDs, it produced no gastric irritation in rats after either acute or chronic oral administration over the range 400-800 mg/kg. The major mechanism of action of Wy-41,770 has yet to be identified but does not seem to involve interference of arachidonic acid metabolism.

Acetates↗

Implantable enzyme capsules for cancer chemotherapy from bakers' yeast cytosine deaminase immobilized on epoxy-acrylic resin and urethane prepolymer.

For trial use in the local chemotherapy of cancer by a combination of cytosine deaminase (EC 3.5.4.1) and 5-fluorocytosine (J. Biotechnol., (1985), 2, 13-21), 40 U of partially purified cytosine deaminase was obtained from 500 g of commercial compressed bakers' yeast. The enzyme, which is unstable, was immobilized to stabilize it by the use of commercial epoxy-acrylic beads (Eupergit C). The immobilized enzyme was made into enzyme capsules with cellulose tubing for dialysis to encapsulate it or urethane polymer to entrap it, which materials are biocompatible. The activity of the intact cellulose capsules thus made was 0.4% that of the immobilized enzyme inside. The enzyme capsules also were stable. Ten days after the cellulose capsules were implanted in rats, 25% of the starting activity remained. When the polyurethane capsules were tested in vitro for 9 mo for thermostability at 37 degrees C, the activity decreased rapidly (with a half-life of 28 d) during the first 4 mo, and then slowly (half-life, about 100 d) during the next 5 mo. A calculation to transform the biphasic decline into a sum of the exponential decline of two components of enzymic activities with different strengths and half-lives showed that the larger half-life was 5 mo.

Antineoplastic Agents↗

Microbiological study of lyophilized dairy kefir.

Preservation of the intrinsic inhibitory power of dairy kefir after lyophilization by testing several desiccation substrates and several regeneration media was studied. The tested cryoprotectors were ribitol, sodium glutamate and glycerol. After lyophilization, the pellets of kefir were regenerated in water or milk. Glycerol was the best cryoprotector because of its high efficiency and its low cost, white sodium glutamate was unsatisfactory.

Animals↗

Comparison of whole blood selenium values and erythrocyte glutathione peroxidase activities of normal individuals on supplementation with selenate, selenite, L-selenomethionine, and high selenium yeast.

The selenium levels and the glutathione peroxidase activity GSH-PX of whole blood and of erythrocytes, respectively, were determined in 139 normal Danes and related to sex and smoking habits. No differences were found in relation to sex apart from a higher GSH-PX activity of females when assayed with tertiary butyl hydroperoxide. Smokers showed significantly lower selenium values than non-smokers (p less than 0.05), but the two groups had identical GSH-PX activities. Individuals from the above-mentioned group were divided into four groups, receiving daily oral doses of 200 micrograms of selenium in the form of selenite, selenate, L-selenomethionine, and selenium as contained in yeast. Whole blood selenium values and the erythrocyte glutathione peroxidase activities were determined during three months of supplementation followed by a withdrawal period of four months. Both the inorganic selenium compounds and the organic derivatives gave rise to steady state levels of GSH-PX after one month of supplementation. However, the selenium levels in the groups receiving organic selenium showed a steady rise during the whole period, whereas those supplemented with inorganic selenium leveled off after a period of one to three months. The data for smokers and nonsmokers revealed identical results when organic selenium was supplemented. However, selenite gave rise to significantly higher selenium levels and GSH-PX activities in smokers than in non-smokers. Less significant (p less than 0.08) elevations of both parameters were also observed among the smokers in the selenate group. By taking both the selenium level and the GSH-PX activity into consideration, organic selenium (i.e., L-(+) selenomethionine) was judged to be more bioavailable than selenite and selenate.

Adult↗

Selenium chemoprevention of liver cancer in animals and possible human applications.

An inverse correlation between geographic distribution of liver cancer incidence and the selenium (Se) contents of whole blood and grains was observed in Qidong county, Jiangsu province, a high liver cancer area of the People's Republic of China. Animal experiments demonstrated that supplementation of Se reduced the incidence of liver cancer in rats exposed to aflatoxin B1. Se was also shown to inhibit the growth of transplanted tumors. A lower incidence of liver preneoplastic alterations and reduction of hepatitis B virus infection in ducks by Se-supplementation was observed, and three pilot studies for a Se-intervention trial on human liver cancer were carried out on the residents of Qidong county. A protective effect on the cellular DNA damage induced by aflatoxin B1 was observed in lympocytes from human with Se-supplements.

Aflatoxins↗

A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.

The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.

Adult↗

Seven cases of fungemia with Saccharomyces boulardii in critically ill patients.

Saccharomyces boulardii (Sb) is a particular strain of Saccharomyces cerevisiae (Sc). This viable yeast is used in intensive care adult patients, delivered in packets of 500 mg, for preventing diarrhea associated with antibiotics or enteral feeding at a regimen of 1-2 g/day. Between June 1996 and October 1998, seven cases of fungemia with Sb occurred in a 12-bed intensive care unit (ICU). All the patients concerned were severely ill patients, mechanically ventilated, treated by broad spectrum antibiotics with central venous catheter and were pretreated with Sb, except for one patient. In this study, Sb was identified by specific mycologic methods and confirmed the genomic identity between isolates of blood culture and yeasts from the treatment packets, contrary to a few other reports concerning Saccharomyces species published in international literature. The hypothesis discussed for explaining these cases of Sb fungemia are: (1) an intestinal translocation of Sb administered at a high dosage in severely ill patients, (2) a contamination of the central venous catheter, especially in the patient not pretreated with Sb and (3) a massive colonization of critically ill patients by the yeast as has been reported for Candida species. We note that cases of fungemia with Sc and Sb have become more and more frequent in the international literature during the last 10 years and we do not recommend administering Sb treatment in critically ill patients.

Aged↗

Hydrolysis of proteins with methanesulfonic acid for improved HPLC-ICP-MS determination of seleno-methionine in yeast and nuts.

In this work, the use of methanesulfonic acid for protein hydrolysis is proposed for evaluation of Se-methionine in yeast, Brazil nuts, and possibly other selenium-rich biological samples. The hydrolysis was carried out by heating the sample with 4 mol L(-1) acid at reflux for 8 h. Two chromatographic techniques (size-exclusion and ion-pairing) coupled with ICP-MS detection were used to compare the release of Se-methionine from proteins by enzymatic (proteinase K, protease XIV) and acid hydrolyses. A more efficient liberation of Se-methionine was observed by acid hydrolysis. For quantification, the sample extracts were introduced onto a C8 Alltima column, and the separation was achieved with a mobile phase containing 5 mmol L(-1) hexanesulfonic acid in citrate buffer (pH 4.5)/methanol (95:5). The results obtained by standard addition showed 816+/-17 micro g g(-1) and 36.2+/-1.5 micro g g(-1) of selenium in the form of Se-methionine in yeast and nuts, respectively (65% and 75% of total selenium).

Chromatography, High Pressure Liquid↗

Selenomethionine content of candidate reference materials.

Selenium has been identified as an antioxidant of importance in the diet. Accurate determination of its chemical forms depends on the availability of suitable reference materials (RMs). Two candidate reference materials for determination of selenomethionine (Semet) in food-related materials, a standard wheat gluten sample (NIST RM 8418 Wheat Gluten) and a commercial selenium enriched yeast, have been examined by use of a gas chromatography-isotope dilution mass spectrometry (IDMS) procedure, after treatment of the matrix with 0.1 mol L(-1) hydrochloric acid containing stannous chloride, addition of CNBr, and extraction with chloroform. This procedure results in cleavage of the CH3Se group to form volatile CH3SeCN. Addition of isotopically enriched 74Semet to an analytical sample enables estimation of the naturally occurring protein-bound 80Semet by IDMS without a protein-digestion process. We found that the Wheat Gluten RM contains a significant amount of Semet as a portion of its assigned value of 2.58 microg Se(total g(-1). Commercial selenium yeast tablets are labeled as containing an elevated level of "organic selenium", usually as Semet. The sample we investigated contained 210 microg Se(total) g(-1) sample as determined separately by IDMS, measuring elemental selenium after digestion. 73% of this total (153 +/- 21 microg Se(semet) g(-1); n = 23) was present as Semet. Thus, these two materials contain significant amounts of their total selenium content as Semet and would be good candidates for further study and characterization as reference materials for determining this important food component. The CNBr reaction used will also enable the determination of Se-(methyl)selenocysteine, the biological role of which is of recent interest. In addition to matrix RMs for Semet, it is important to have standard materials of the pure substance. We have examined a sample of a candidate standard material of selenomethionine being prepared by the USP. It was confirmed that this material is pure selenomethionine.

Cold Temperature↗

Saccharomyces cerevisiae fungemia in a neutropenic patient treated with Saccharomyces boulardii.

A case of Saccharomyces fungemia in an 8-month-old baby affected by acute myeloid leukemia while receiving intensive chemotherapy is reported. The patient was receiving prophylaxis treatment with Saccharomyces boulardii capsules (Codex) to prevent diarrhea, which is commonly associated with this type of chemotherapy. Fever spiked just the day after ending the chemotherapy course, and a strain of Saccharomyces cerevisiae was isolated from blood culture although the patient was also receiving antifungal prophylaxis with fluconazole. The patient recovered, though still neutropenic, with amphotericin-B and removal of the central venous catheter. The common biochemical characteristics make it difficult to differentiate between the strain of Saccharomyces cerevisiae and that of Saccharomyces boulardii with routine methods. In other cases, authors demonstrated an identity between the two strains with a more detailed analysis. These reports raise concern about the potential side effects of such biotherapeutic agents.

Antifungal Agents↗

Possible role of catheters in Saccharomyces boulardii fungemia.

Four cases of Saccharomyces boulardii fungemia, a very rare side effect of Saccharomyces boulardii therapy, are reported. The clinical impact of Saccharomyces boulardii infection appeared to be moderate. However, even though organ involvement was never demonstrated, septic shock with no other etiology was observed in one of our patients. All patients had an indwelling vascular catheter. Contamination of the air, environmental surfaces, and hands following the opening of a packet suggests that catheter contamination may have been a source of infection. To prevent catheter contamination it is recommended that packets or capsules of Saccharomyces boulardii be opened with gloves, outside the patient's room.

Adult↗

Subplantar yeast injection induces a non-naloxone reversible antinociception in spontaneously hypertensive rats.

Spontaneously hypertensive (SH), Wistar Kyoto (WKY) or Sprague-Dawley (SD) rats were tested for their responsiveness to noxious mechanical pressure before and after a subplantar yeast injection to the right rear paw. Prior to the yeast injection, hypertensive animals were less responsive to pain relative to normotensive animals, as seen in the significantly greater pre-yeast latencies of SH compared to WKY or SD rats. Subplantar yeast injection produced hyperreactivity in the inflamed paws of WKY or SD rats, with no effect on the contralateral non-injected paw. However, identical subplantar yeast injections to hypertensive animals produced a robust, long-lasting antinociceptive effect in both rear paws of SH rats. This effect was not reversed by naloxone (opiate antagonist), labetalol (beta-blocker/vasodilator antihypertensive), or hydralazine (peripheral vasodilator antihypertensive); the antinociception was not potentiated by thiorphan (enkephalinase inhibitor). However, the alpha 2-receptor antagonist yohimbine (0.1-5 mg/kg s.c.), produced a dose-related reversal of the yeast-induced antinociception in SH rats. These results suggest that the subplantar yeast injection is triggering descending noradrenergic pain inhibitory pathways in SH rats.

Animals↗