Sake yeast induces the sleep-promoting effects under the stress-induced acute insomnia in mice.

Sleep deprivation induces adverse effects on the health, productivity, and performance. The individuals who could not get enough sleep temporarily experience the symptoms of an induced acute insomnia. This study investigated the efficacy of sake yeast in treatment of acute insomnia in mice. The results of this study showed that sake yeast induced a significant dose-dependent wake reduction, a rapid eye movement (REM) and a non-REM (NREM) sleep enhancement during the first 6 h after the oral administration of sake yeast with locomotor activity and core body temperature decreases under the stressful environment in a new cage. In fact, the wake amounts at 3 h and 6 h were significantly reduced after the oral administration of sake yeast compared with the vehicle. The NREM sleep amounts at 3 h and 6 h significantly increased after the administration of sake yeast compared with the vehicle. The REM amount at 6 h significantly increased after the administration of sake yeast compared with the vehicle, but not at 3 h. The previous study suggested that the sleep-promoting effects of sake yeast could be referred from the activating effect of adenosine A2A receptor (A2AR). In summary, the sake yeast is an A2AR agonist and may induce sleep due to its stress-reducing and anti-anxiety properties. Further verification of the involvement of adenosine in the pathophysiology of insomnia is needed.

Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves.

The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin ß-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial.

BACKGROUND: Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis. METHODS/DESIGN: The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. INCLUSION CRITERIA: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. EXCLUSION CRITERIA: previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 µg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 µg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events. DISCUSSION: In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02013479.

Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial.

Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 µg/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.

The influence of selenium-enriched milk proteins and selenium yeast on plasma selenium levels and rectal selenoprotein gene expression in human subjects.

Certain forms of dietary Se may have advantages for improving human Se status and regulating the risk for disease, such as cancers, including colorectal cancer (CRC). The present study compared the effects of a Se-enriched milk protein (dairy-Se) with a Se-rich yeast (yeast-Se) on plasma Se levels and rectal selenoprotein gene expression since we reasoned that if these genes were not regulated, there was little potential for regulating the risk for CRC in this organ. A total of twenty-three healthy volunteers with plasma Se in the lower half of the population range were supplemented with dairy-Se (150 µg/d) or yeast-Se (150 µg/d) for 6 weeks, followed by 6 weeks of washout period. Blood was sampled every 2 weeks, and rectal biopsies were obtained before and after Se supplementation and after the washout period. Plasma Se levels and glutathione peroxidase (GPx) activity, and rectal mRNA of selenoprotein P (SeP), cytosolic GPx-1 (GPx-1), gastrointestinal GPx-2 (GPx-2) and thioredoxin reductase-1 (TrxR-1) were measured. Plasma Se levels increased rapidly in both Se groups (P < 0·001); plasma GPx activity was not significantly changed. Rectal SeP mRNA increased at 6 weeks compared with baseline in both Se groups (P < 0·05); only dairy-Se resulted in a sustained elevation of SeP after the washout period (P < 0·05). Rectal GPx-1 and GPx-2 mRNA were higher with dairy-Se (P < 0·05) than with yeast-Se at 6 weeks. In conclusion, three rectal selenoprotein mRNA were differentially regulated by dairy-Se and yeast-Se. Changes in rectal selenoproteins are not predicted by changes in plasma Se; dairy-Se effectively regulates the expression of several rectal selenoproteins of relevance to the risk for CRC.

[Biotherapeutic use of yeasts--importance of probiotic products]. / Aplicatiile bioterapeutice ale drojdiilor--importanta produselor probiotice.

Besides their important biotechnological and industrial applications, yeasts have been used during the last years, in obtaining probiotic products, along with lactic acid bacteria and various enzymes. Our study deals with some aspects regarding the use of yeasts as animal and human probiotics, and their possible mechanisms of action. Also, we present information on probiotic products synthesized by international and national companies. Finally, there are described future prospective of research concerning the applications of recombinant yeast strains as basis for obtaining new bio-drugs. In conclusion, the data comprised in this paper, presents an interesting argument for using yeasts as biotherapeutic agents, an alternative to conventional treatments.

Yeast therapy for the treatment of breast cancer: a nude mice model study.

BACKGROUND: Studies have demonstrated that phagocytosis of yeast induces apoptosis in human breast cancer (BC) cells in vitro. Here, the in vivo apoptotic activity of the S. cerevisiae against human BC (MCF-7) bearing nude mice was investigated. MATERIALS AND METHODS: MCF-7 cells were injected into nude mice. Mice were then injected intratumorally with yeast on a weekly basis for 45 days. Tumors were excised and analyzed for phagocytosis/apoptosis via histopathological staining, electron microscopy (EM), and flow cytometry. RESULTS: The results demonstrate the ability of MCF-7 cells to phagocytize yeast and the effectiveness of yeast in triggering apoptosis in MCF-7 cells in vivo. Histological sections of yeast-treated tumors show extensive tumor apoptosis/fibrosis. EM studies clearly show apoptotic MCF-7 cells with nuclear margination and fragmentation. Flow cytometry confirmed this result. No noticeable adverse side-effects from the yeast treatment were observed. CONCLUSION: S. cerevisiae is a promising anti-cancer agent that induces significant levels of apoptosis in malignant cells in vivo. However, yeast therapy for the treatment of breast cancer has yet to pass controlled clinical trials.

Saccharomyces boulardii and infection due to Giardia lamblia.

Therapy with metronidazole is the recommended option in giardiasis. However, some clinical trial reports suggest the appearance of drug resistance to explain therapeutic failure. Several investigations have been carried out on the effect of probiotic microorganisms for preventing or treating gastrointestinal diseases, but little is known about their efficacy against protozoal infections. The principal objective of our study was to evaluate the efficacy of Saccharomyces boulardii against Giardia lamblia infections. A double-blind, placebo-controlled study was carried out on adult patients with giardiasis. Group 1 (30 patients) included metronidazole 750 mg 3 times daily along with S. boulardii capsules (250 mg b.i.d. orally) for 10 d while group 2 (35 patients) was treated with metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d. Patients were re-examined at 2 and 4 weeks after treatment, and stool examinations were performed. At week 2, G. lamblia cysts were detected in 6 cases (17.1%) of group 2 and none in group 1. At the end of the fourth week, presence of the cysts continued in the same 6 cases in group 2 (control group). These findings indicated that S. boulardii may be effective in treating giardiasis when combined with metronidazole therapy.

Saccharomyces cerevisiae fungemia in a head and neck cancer patient: a case report and review of the literature.

We report the case of a 65-year old male who developed Saccharomyces cerevisiae fungemia after completing a course of concomitant chemotherapy and radiation therapy for head and neck carcinoma. He had grade IV oral mucositis, and received Saccharomyces boulardii (Perenterol) orally as treatment for aseptic diarrhoea just before the onset of fungemia. We discuss the epidemiology and pathology of Saccharomyces cerevisiae in the cancer patient population.

Effects of combined selenium and vitamin E administration on DNA in Walker tumor bearing Wistar rat exposed to cytostatic acute treatment.

Previous studies have showed that organic Se and Vitamin E have a significant protective effect when administered in combination with cytostatics. This paper reports the investigation on effects of mixed administration Orgasel 50 and Vitamin E in Wistar rat with experimentally induced Walker tumor under acute cytostatic treatment, with emphasis on two aspects: a) the influence of antioxidants upon liver unscheduled DNA biosynthesis under cytostatic (Lomustin) acute aggression; and b) the potential improvement of cytostatic effects by antioxidants treatment in tumor. Two lots of animals were used: lot 1 - Orgasel 50 and Vitamin E administered 7 days before the initiation of tumor induction and lot 2 - the antioxidants were concomitantly administered with tumor cell inoculation. The Walker tumor (an epithelial carcinoma) cells were subcutaneously injected (5 x 10(6) cells/0.5 ml in isotonic saline solution); the first tumor nodules appeared in 4 days; the tumor has reached the appropriate dimensions in 12 days. The unscheduled DNA biosynthesis caused by Lomustin in rat liver as well as the replicative DNA biosynthesis taking place in Walker tumor cells were assessed radioisotopically by measuring the uptake of 3H-Thymidine (200 microCi / 100 g.b.w.). Our observations regarding the role of antioxidant treatment suggest: 1) a benefic effect on DNA alkylant-induced lesions, expressed by a decrease in the level of 3H-Thymidine uptake in liver and, 2) an increase of the inhibitory activity of cytostatic on DNA replication biosynthesis in tumor cells, suggested by lower 3H-Thymidine incorporation in tumor cells. The most significant results were showed in both analyzed tissues, when the Orgasel 50 + Vitamin E administration begins at the same time with the tumor cell inoculation. These findings clearly show the organic Se salts and Vitamin E constitute a valuable adjuvant in anticancer medication, increasing the interest for the application of these antioxidants in cancer therapy and prevention.

Influence of selenium-enriched yeast supplementation on biomarkers of oxidative damage and hormone status in healthy adult males: a clinical pilot study.

The mechanisms responsible for the protective role of selenium against the development of prostate cancer remain to be determined (L. C. Clark et al., J. Am. Med. Assoc., 276: 1957-1963, 1996). In the present study, we tested the hypothesis that selenium supplementation reduces oxidative stress. A secondary aim was to determine whether selenium-induced changes in testosterone (T) metabolism may also be involved. To this end, we conducted a double-blind, randomized, placebo-controlled trial of 247 micro g selenium/day administered p.o. in the form of Se-enriched yeast. Study subjects were 36 healthy adult males, 11 blacks and 25 whites, 19-43 years of age. Supplementation occurred over the first 9 months, after which all subjects were placed on placebo for an additional 3 months. Blood and urine were collected at baseline and after 3, 9, and 12 months. In the selenium group, plasma selenium levels were 2-fold higher than baseline values after 3 and 9 months and returned to 136% of baseline after 12 months (P < 0.0001), whereas in the placebo group, levels were unchanged. A 32% increase in blood glutathione (GSH) levels was observed after 9 months in the selenium group only (P < 0.05). This change coincided with a 26% decrease in protein-bound GSH (bGSH) and a 44% decrease in bGSH:GSH ratios (P < 0.05). The changes in GSH and bGSH were highly correlated with changes in plasma selenium concentrations and may reflect a decrease in oxidative stress. No changes were observed in either group for plasma T, dihydrotestosterone (DHT) or DHT:T ratios, suggesting that selenium had no effect on the alpha-reductase involved in the conversion of T to DHT. A small but significant decrease in prostate-specific antigen levels was observed after 3 and 9 months (P < 0.001), and this difference disappeared after 12 months. Future trials will test the above hypothesis in prostate cancer patients and in subjects at high risk for prostate cancer.

[Effect of dietary selenium and germanium on the precancerous lesion in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine].

N-Methyl-N'-nitrosoguanidine (MNNG) was administered (100 mg/L) in drinking water in 100 Wistar rats for 24 weeks to induce the precancerous lesion in glandular stomach. 77 rats with the precancerous lesion in glandular stomach were divided into 3 groups randomly at the 25 thweek. Yeast selenium (Yse, 4 mg/L) and carboxyethyl germanium sesquioxide (Ge-132, 600 mg/L) in drinking water were administered respectively in the corresponding treatment groups: 100 ml/MNNG in drinking water was administered in the treatment group, and 100 ml/MNN in drinking water was administered in the treatment group and control group for another 5 weeks. The experiment ended at the end of the 37th week. The results showed that the incidence of glandular stomach cancer in the Yse group was significantly lower than that in the control group; the infiltrating depth of glandular stomach cancer in the Yse group and the Ge-132 group was remarkably shallower than that in the control group. These findings suggest that Yse and Ge-132 have some preventive effect on the precancerous lesion in rat glandular stomach induced by MNNG.

A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease.

OBJECTIVE--To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile-associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). DESIGN--A double-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. SETTING--National referral study of ambulatory or hospitalized patients from three main study coordinating centers. PATIENTS--A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. INTERVENTION--Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. MAIN OUTCOME MEASURE--Recurrence of active CDD. RESULTS--A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P = .04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P = .86). There were no serious adverse reactions associated with S boulardii. CONCLUSIONS--The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD.

[The effect of different types of immunocorrective therapy on the clinical course of chronic myeloleukemia]. / Vliianie razlichnykh vidov immunokorrigiruiushchei terapii na klinicheskoe techenie khronicheskogo mieloleikoza.

Influence of various patterns of immunocorrective therapy on clinical course of chronic myeloleukemia (CML) was studied. It was shown that combinations of drugs with different pharmacological effects provide more than 5-fold decrease in incidence of infection-related complications and promote rapid recovery from infections during antibacterial treatment.

[Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer].

Two populations with high risk primary liver cancer (PLC), one of 226 cases with HBsAg carriers and another of 3849 first-relatives in the pedigree with high incidence of PLC, were randomly divided into the supplementing selenium group (selenium yeast 200 g Se1Tab/day) and the control group (common yeast 1 Tab/day), and were followed-up for four years and two years respectively. In the population with HBsAg carriers, no liver cancer occurred in the supplementing selenium group; where as the liver cancer incidence rate was 1573.03/10(5) in the control group. Among the first relatives. The liver cancer incidence rate in the supplementing selenium group was 219.37/10(5); and 553.15/10(5) in the control group. The results showed that the incidence of PLC in the supplementing selenium group was significantly lower than in the control group. This study indicates that selenium has distinct anti-PLC effect.

[The characteristics of the humoral interaction of lymphocytes with neutrophilic granulocytes of the peripheral blood in patients with chronic lympholeukemia under the influence of Proper-Myl]. / Osobennosti gumoral'nogo vzaimodeistviia limfotsitov s neitrofil'nymi granulotsitami perifericheskoi krovi u bol'nykh khronicheskim limfoleikozom pod vliianiem proper-mila.

A study of 32 patients with chronic lympholeucosis (CL) revealed a reduction of the number of phagocytosing neutrophil granulocytes and a reduction of production of humoral mediators by lymphocytes that stimulated the phagocytic function of granulocytes. It is shown that treatment by usually used cytostatic agents did not essentially effect the investigated values. Inclusion of proper-myl in the treatment course of patients with chronic lympholeucosis furthered increase of the number of phagocytosing neutrophil granulocytes and an increased production of humoral mediator stimulating the phagocytic activity of granulocytes.

[Effect of proper-myl on humoral interactions between activated lymphocytes and neutrophils in patients with myeloproliferative diseases]. / Vliianie proper-mila na kharakter gumoral'nogo vzaimodeistviia aktivirovannykh limfotsitov i neitrofilov krovi u bol'nykh mieloproliferativnymi zabolevaniiami.

The lymphokine synthesizing function of peripheral blood lymphocytes (PBL) was studied in 22 patients with chronic myeloid leukemia (CML), 28 patients with subleukemic myelosis (SLM) and 15 healthy persons. The index of the neutrophil stimulation (INS) in CML (1.73 +/- 0.068) and SLM (1.458 +/- 0.004) was statistically significantly lower than that in the healthy persons (2.6 +/- 0.07). The use of proper-myl in the complex therapy markedly increased the ability of PBL to produce the factor stimulating phagocytic activity of neutrophils (INS 1.94 +/- 0.04 and 1.832 +/- 0.092). On the basis of the findings it was recommended to use proper-myl for prevention and treatment of infectious complications.

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.