Increase in total blood leukocyte count following intranasal administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with cyclophosphamide-induced leukopenia

We investigated the effects of intranasal (i.n.) administration of recombinant human granulocyte colony-stimulating factors (rhG-CSF) on the total count of leukocytes in peripheral blood (total blood leukocyte count) of rabbits with leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was administered intravenously, the total blood leukocyte count decreased to levels below 5000/microliters approximately 4 d after the initiation of CPA multiple dosing. The decreased level of the total blood leukocyte count was maintained throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA-treated rabbits via i.n. administration of aqueous preparations containing rhG-CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte count increased from levels below 5000/microliters to the normal physiological level following i.n. administration of rhG-CSF preparation and reduced the period of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was more effective in increasing the total blood leukocyte count. It is suggested that i.n. administration of rhG-CSF is promising for reducing the risk of cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.     

Rice Protein Isolates Produced by the Two Different Methods Lower Serum Cholesterol Concentration in Rats Compared with Casein

Highly purified rice protein isolates (RPI) were prepared by an alkaline extraction–acid precipitation method (E-RPI) and by an α-amylase treatment to remove starch (T-RPI). Biological values of these RPI were significantly lower than that of casein. Serum cholesterol concentrations were compared among groups of rats fed (per kg diet) 200, 300 or 400 g E-RPI, 400 g T-RPI, 250 or 400 g casein kg⁻¹ or 400 g soya bean protein isolate (SPI). With all the diets containing 400 g protein kg⁻¹ diet, growth rates of rats were the same. At this level, E-RPI, T-RPI and SPI diets produced significantly lower serum cholesterol concentrations than the casein diet. Faecal bile acid plus neutral steroid excre-tion was significantly higher in rats fed the 400 g kg⁻¹ T-RPI or 400 g kg⁻¹ SPIdiets compared with rats fed the 400 g kg⁻¹ casein diet. On the other hand, the 400 g kg⁻¹ E-RPI diet did not increase steroid excretion. Plasma cholesterol concentrations in rats fed diets with amino acid mixtures simulating SPI and E-RPI were also significantly lower than that of rats fed the diet with an amino acid mixture simulating casein even though the faecal excretions of total bile acids were the same amongst groups. These results support the view that RPI are hypocholesterolaemic relative to casein and at least the hypocholesterolaemic effects of E-RPI would be independent of interruption of the enterohepatic circulation of endogenous steroids.     

Resistant proteins alter cecal short-chain fatty acid profiles in rats fed high amylose cornstarch

The objective of this study was to examine the physiologic importance of undigested protein on cecal fermentation in rats fed a low (LAS) and high (HAS) amylose cornstarch. In Experiment 1, rats were fed diets containing LAS (655 g/kg diet) with one of four protein sources: casein, rice (RP), potato (PP) or soybean protein (SP) at 250 g/kg diet for 15 d. Apparent digestibilities of casein, RP, SP and PP were 96, 94, 93 and 92%, respectively. In rats fed the LAS diet with casein, acetate, propionate and succinate were the major cecal organic acids. The succinate pools in rats fed RP or SP were significantly lower than in those fed casein, whereas butyrate did not differ. Butyrate was significantly higher in rats fed PP, but succinate was the same as in rats fed casein. In Experiment 2, rats were fed diets containing HAS (200 g/kg diet) with one of the four protein sources at 250 g/kg diet for 10 d. HAS was substituted for the same amount of LAS. In rats fed the HAS diet, succinate was the major acid in rats fed casein; in rats fed RP or PP, however, the pools of this acid were significantly lower than in those fed casein, whereas butyrate was significantly higher in rats fed RP or PP. Fecal starch excretion was significantly lower in rats fed RP or PP than in those fed casein. In Experiment 3, rats were fed the casein-HAS diet with graded levels of PP (0, 10, 30, 50, 100 and 250 g/kg diet) for 14 d. The PP was substituted for the same amount of casein. Cecal butyrate was low in rats fed up to 100 g of PP/kg diet and then rose with 250 g of PP/kg diet. In Experiment 4, ileorectostomized rats were used and fed the same diets described in Experiment 3 for 9 d. The ileal starch/nitrogen ratio declined with increasing dietary PP, due solely to greater nitrogen excretion, whereas starch excretion was unaffected. In Experiment 5, rats were fed the casein-HAS diet with or without 60 g of artificial resistant protein/kg diet for 10 d. The resistant protein (apparent digestibility, 63%) was substituted for the same amount of casein. Rats fed the casein-HAS diet with resistant protein had significantly greater cecal butyrate and lower succinate than those fed the casein-HAS diet. These data show that large bowel fermentation of starch is altered by dietary protein. They support the hypothesis that nondigested protein, namely, resistant protein, may control fermentation efficiency as well as the fermentation profile of HAS, possibly as a result of a change in microflora through the change in the ratio of starch to nitrogen in the cecum.     

Profiles of ion beams and plasma parameters on a multi-frequencies microwaves large bore electron cyclotron resonance ion source with permanent magnets

In order to contribute to various applications of plasma and beams based on an electron cyclotron resonance, a new concept on magnetic field with all magnets on plasma production and confinement has been proposed with enhanced efficiency for broad and dense ion beam. The magnetic field configuration consists of a pair of comb-shaped magnet surrounding plasma chamber cylindrically. Resonance zones corresponding for 2.45 GHz and 11-13 GHz frequencies are positioned at spatially different positions. We launch simultaneously multiplex frequencies microwaves operated individually, try to control profiles of the plasma parameters and the extracted ion beams, and to measure them in detail.     

Improvement of efficiency and temperature control of induction heating vapor source on electron cyclotron resonance ion source

An electron cyclotron resonance ion source (ECRIS) is used to generate multicharged ions for many kinds of the fields. We have developed an evaporator by using induction heating method that can generate pure vapor from solid state materials in ECRIS. We develop the new matching and protecting circuit by which we can precisely control the temperature of the induction heating evaporator. We can control the temperature within ±15?°C around 1400?°C under the operation pressure about 10(-4) Pa. We are able to use this evaporator for experiment of synthesizing process to need pure vapor under enough low pressure, e.g., experiment of generation of endohedral Fe-fullerene at the ECRIS.     

Growth is compromised in rats fed ozone-treated casein

Modified casein containing few phenylalanine residues and no other aromatic amino acid residues was obtained by ozonolysis of casein. Although 68% of phenylalanine was decomposed by ozonolysis of casein, ozonolysis caused alterations beyond the destruction of aromatic amino acid residues. Nearly the same degree of decomposition of amino acid residues was observed in casein ozonated after predigestion by pepsin. Rats were fed diets containing 8% casein supplemented with methionine and aspartic acid (8C-AA), 8% ozonated casein supplemented with methionine and free amino acids lost by ozonolysis (8OC-AA), 8% casein ozonated after predigestion by pepsin supplemented with methionine and free amino acids lost during preparation (8POC-AA) or 7.6% amino acid mixture. The growth of rats fed the 8OC-AA diet was significantly lower than that of those fed 8C-AA or 7.6AA diets. The growth of rats fed the 8POC-AA diet was comparable to growth of those fed 8OC-AA. The biological values of the 8OC-AA and 8POC-AA were comparable to that of 8C-AA, but true digestibility of 8OC-AA was significantly lower than that of 8C-AA. True digestibility 8POC-AA was significantly improved relative to 8OC-AA, but the growth of rats fed 8POC-AA was not improved relative to that of those fed 8OC-AA. Kidney and cecum weights of rats fed 8OC-AA and 8POC-AA were significantly heavier than those of the 8C-AA-fed group, although histopathological examination of kidneys showed no deterioration compared to that of the 8C-AA-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)     

A rice protein isolate alters 7,12-dimethylbenz[alpha]anthracene-induced mammary tumor development in female rats

The effects of a rice protein isolate (RPI) on 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary tumor progression were investigated in female Sprague-Dawley rats. At 6 weeks of age, rats were fed a casein, RPI or soybean protein isolate (SPI) diet, respectively. After 1 week, DMBA was administered orally at the dose of 30 mg/kg body weight. The mean tumor number per tumor-bearing rat at autopsy was significantly lower only in rats fed RPI than in those fed casein. Palpable tumors at the mid point of the experiment were significantly lower in rats fed RPI and SPI than in those fed casein. Serum estradiol-17 beta concentrations were lower in rats fed the SPI (but not in those fed RPI) than in those fed casein. In a further experiment, no differences were found in hepatic microsomal DMBA-arylhydrocarbon hydroxylase activity after 7 days of feeding the respective diets. These results suggest that RPI exerts its inhibitory effect on DMBA-induced mammary tumorigenesis irrespective of changes in circulating estrogens or modulation of hepatic DMBA metabolism.     

The degree of polymerization of inulin-like fructans affects cecal mucin and immunoglobulin A in rats

ABSTRACT:  Cecal amounts of mucin and immunoglobulin A (IgA) were examined through the cecal fermentation pattern in Wistar (WS) or Sprague–Dawley (SD) rats fed inulin-type fructans differing in their degree of polymerization (DP). The animals were fed a control diet or a diet containing one of the fructans with an average DP of 4, 8, 16, or 23, at 60 g/kg diet for 10 d. Cecal fermentation products substantially differed between WS and SD rats fed DP8 fructan, with short-chain fatty acids (SCFAs) as the major organic acids in the former but lactate predominating in the latter. Cecal fermentability of fructans in both strains generally decreased with increasing DP of fructans, and this was especially manifest in reduction of the amounts of lactate in DP16 and 23. In WS rats, cecal mucin and IgA were greater in all fructan groups than in the control group. In SD rats, cecal mucin was greater only in the DP8, 16, and 23 groups as compared to the control group, while IgA was greater in the DP4 and 8 groups. In both strains, cecal mucin correlated with the sum of cecal SCFAs, but not with lactate, succinate, or total organic acids. In contrast, only cecal lactate correlated with cecal IgA in both strains. The present study shows that the different fermentation patterns of fructans affect cecal mucin and IgA; mucin is likely to respond to cecal SCFA production, whereas IgA increases when fermentation occurs rapidly and lactate is a major fermentation product.     

Binding characteristics of KNI-272 to plasma proteins, a new potent tripeptide HIV protease inhibitor

The binding characteristics of KNI-272, a potent and selective human immunodeficiency virus (HIV) protease inhibitor, were evaluated in rat and human plasma, and in solutions of human alpha 1-acid glycoprotein (AAG) and human serum albumin (HSA). The unbound fractions (Fu) of KNI-272 were 12.13 and 2.24% in rat and human plasma, respectively, at the drug concentration of 1.0 microgram mL-1. Although KNI-272 binds to both AAG and HSA, the Fu of KNI-272 in AAG solution was 1.83%, and only one-quarter of that in HSA solution (Fu = 6.78%). Binding displacing agents, such as disopyramide, warfarin, diazepam, and digitoxin, were used to determine the binding site of KNI-272 on these plasma proteins. The Fu of KNI-272 in AAG solution increased 14-fold when disopyramide was added to the AAG solution. In addition, warfarin, diazepam, and digitoxin were added to HSA solution as representative drugs bound to distinct binding sites on HSA, namely sites I, II, and III, respectively. The Fu values of KNI-272 in HSA solution significantly increased when warfarin and diazepam were added. In particular, with the addition of warfarin to HSA solution, the Fu of KNI-272 increased to 16%. The modified Scatchard plots of KNI-272 binding to AAG and HSA both showed biphasic curves, and the KNI-272 binding sites at low concentration range on AAG and HSA disappeared with the addition of disopyramide and warfarin, respectively. Therefore, it is considered that KNI-272 binds to the identical site as disopyramide on AAG and site I on HSA in the low KNI-272 concentration range. By comparing the KNI-272 binding parameters obtained in human plasma and these protein solutions, we can assume that KNI-272 binding at low concentration in human plasma is mainly concerned with the binding on AAG. As KNI-272 concentration in plasma increases, HSA becomes concerned with KNI-272 binding.