Effect of Saccharomyces cerevisiae UFMG A-905 in a murine model of food allergy

2020 ◽  
Vol 11 (3) ◽  
pp. 255-268
Author(s):  
V.C. Miranda ◽  
S.S. Santos ◽  
H.C. Assis ◽  
A.M.C. Faria ◽  
M.F. Quintanilha ◽  
...  

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.

Acta Naturae ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 125-128
Author(s):  
V. A. Palikov ◽  
S. S. Terekhov ◽  
Yu. A. Palikova ◽  
O. N. Khokhlova ◽  
V. A. Kazakov ◽  
...  

The development of antidotes to organophosphate poisons is an important aspect of modern pharmacology. Recombinant acetylcholinesterase and butyrylcholinesterase are effective DNA-encoded acceptors of organophosphate poisons and, in particular, pesticides. Here, we present the results of a study on the effectiveness of recombinant butyrylcholinesterase (BChE) in modeling organophosphate poisoning caused by oral administration of paraoxon at a dose of 2 mg / kg. The study showed a high activity of BChE as a protective agent for subchronic anticholinesterase poisoning in an in vivo model. The administration of BChE in a dose of 20 mg / kg allows one to avoid mortality, and also contributed to rapid recovery after model poisoning.


1999 ◽  
Vol 77 (11) ◽  
pp. 886-895 ◽  
Author(s):  
Gordon Bolger ◽  
Jean-Claude Vigeant ◽  
Francine Liard ◽  
Bruno Simoneau ◽  
Diane Thibeault ◽  
...  

The human renin infused rat model (HRIRM) was used as an in vivo small-animal model for evaluating the efficacy of a collection of inhibitors of human renin. The intravenous infusion of recombinant human renin (2.4 µg·kg-1·min-1) in the ganglion-blocked, nephrectomized rat produced a mean blood pressor response of 47 ± 3 mmHg (1 mmHg = 133.3 Pa), which was reduced by captopril, enalkiren, and losartan in a dose-dependent manner following oral administration, with ED50 values of 0.3 ± 0.1, 2.5 ± 0.9, and 5.2 ± 1.6 mg/kg, respectively. A series of peptidomimetic P2-P3 butanediamide renin inhibitors inhibited purified recombinant human renin in vitro in a concentration-dependent manner, with IC50 values ranging from 0.4 to 20 nM at pH 6.0, with a higher range of IC50 values (0.8-80 nM) observed at pH 7.4. Following i.v. administration of renin inhibitors, the pressor response to infused human renin in the HRIRM was inhibited in a dose-dependent manner, with ED50 values ranging from 4 to 600 µg/kg. The in vivo inhibition of human renin following i.v. administration in the rat correlated significantly better with the in vitro inhibition of human renin at pH 7.4 (r = 0.8) compared with pH 6.0 (r = 0.5). Oral administration of renin inhibitors also resulted in a dose-dependent inhibition of the pressor response to infused human renin, with ED50 values ranging from 0.4 to 6.0 mg/kg and the identification of six renin inhibitors with an oral potency of <1 mg/kg. The ED50 of renin inhibitors for inhibition of angiotensin I formation in vivo was highly correlated (r = 0.9) with the ED50 for inhibition of the pressor response. These results demonstrate the high potency, dose dependence, and availability following oral administration of the butanediamide series of renin inhibitors.Key words: renin-angiotensin system, recombinant human renin, rat, renin inhibitors.


Author(s):  
S.M. El Hassan ◽  
C.J. Newbold ◽  
R.J. Wallace

It has been suggested that the mechanism by which yeast cultures (YC), based on Saccharomyces cerevisiae, improve ruminant production is by stimulating rumen fibre digestion and microbial protein flow from the rumen. Both of these effects have in turn been related to the increases in bacterial growth in the rumen observed when YC is added to the diet. However, although it is has been shown that the effectiveness of YC in improving productivity is influenced by the composition of the diet fed (Williams and Newbold, 1990), little is known about how the ability of YC to stimulate bacterial numbers in the rumen is affected by diet composition.The effect of diet on the stimulation of bacterial numbers in the rumen by YC was investigated in the rumen simulation technique (Rusitec). Grass silage was prepared from a sward of perennial rye-grass, without the use of a preservative. Fresh grass was collected from the sward prior to ensilage and stored at -20°C. Grass (5.96 g dry matter (DM) /day) and grass silage (6.54 g DM/ day) were compared alone or supplemented with 500 mg / day YC (Yea-sacc, Alltech), in triplicate, in an experiment lasting 21 days.Four rumen cannulated sheep, allowed ad lib access to grass silage, were used to investigate further the effects of YC on bacterial numbers in the rumen in vivo. The effects of YC (4 g/ day) were investigated in a 2 × 2 factorial design with 28 day periods.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2209 ◽  
Author(s):  
Yuri Park ◽  
Min-Ho Park ◽  
Jin-Ju Byeon ◽  
Seok-Ho Shin ◽  
Byeong ill Lee ◽  
...  

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC–MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus™ simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus™ was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.


1998 ◽  
Vol 9 (2) ◽  
pp. 203-210 ◽  
Author(s):  
U Haberstroh ◽  
K Stilo ◽  
J Pocock ◽  
G Wolf ◽  
U Helmchen ◽  
...  

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.


Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3559-3566 ◽  
Author(s):  
C. Decourt ◽  
A. Rocca ◽  
F. Bridoux ◽  
F. Vrtovsnik ◽  
J.L. Preud’homme ◽  
...  

We have designed an in vivo model in which murine hybridoma cell clones producing human Ig light chains (LC) are administred to mice. Depending on which monoclonal LC is expressed, this model mimicks either cast myeloma nephropathy or the pathological condition defined as myeloma-associated Fanconi’s syndrome (FS) with LC crystallization. Morphological alterations of the kidney cells are thus obtained in mice. All studied LC are closely related human monoclonal VκI proteins, which differ by a limited number of substitutions within the variable region. In the case of an FS monoclonal LC, we show that limited changes introduced through site-directed mutagenesis in the variable domain may suppress formation of intracellular crystals within tubular cells. We also show that multiple peculiarities of the variable region are simultaneously needed to allow LC crystallization; this property thus likely results from a unique LC tridimensional conformation imposed by concomitant somatic mutations of a specific germinally encoded framework.


Parasitology ◽  
2019 ◽  
Vol 147 (3) ◽  
pp. 303-309 ◽  
Author(s):  
L. Nishi ◽  
P. L. Santana ◽  
F. F. Evangelista ◽  
L. F. Beletini ◽  
A. H. Souza ◽  
...  

AbstractThis study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI – non-infected, GII – infected, GIII – infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg−1 body weight day−1), GIV and GV – infected and treated with rosuvastatin 10 and 40 mg kg−1 body weight day−1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.


2021 ◽  
Author(s):  
Panagiotis Chatzistergos ◽  
Nachiappan Chockalingam

Abstract This proof-of-concept study demonstrates that repetitive loading to the pain threshold can safely recreate overloading-induced soft tissue damage and that localised tissue stiffening can be used as a marker for injury. This concept was demonstrated here for the soft tissue of the sole of the foot where it was found that repeated loading to the pain threshold led to long-lasting statistically significant stiffening in the areas where pressure was most intense. Loading at lower magnitudes did not have the same effect. This method can shed new light on the aetiology of overloading injury in the foot to improve the management of conditions such as diabetic foot ulceration and heel pain syndrome. At the same time, the presented concept can also enable the direct assessment of subject-specific thresholds for overloading in other soft tissues which are sensitive to pain, accessible for imaging and can be loaded in a clinically relevant manner.


2007 ◽  
Vol 73 (11) ◽  
pp. 3566-3574 ◽  
Author(s):  
G. Garrait ◽  
J. F. Jarrige ◽  
S. Blanquet ◽  
E. Beyssac ◽  
M. Alric

ABSTRACT An innovative “biodrug” concept, based on the oral administration of living recombinant microorganisms, has recently emerged for the prevention or treatment of various diseases. An engineered Saccharomyces cerevisiae strain expressing plant P450 73A1 (cinnamate-4-hydroxylase [CA4H] activity) was used, and its survival and ability to convert trans-cinnamic acid (CIN) into p-coumaric acid (COU) were investigated in vivo. In rats, the recombinant yeast was resistant to gastric and small intestinal secretions but was more sensitive to the conditions found in the large intestine. After oral administration of yeast and CIN, the CA4H activity was shown in vivo, with COU being found throughout the rat's digestive tract and in its urine. The bioconversion reaction occurred very fast, with most of the COU being produced within the first 5 min. The gastrointestinal sac technique demonstrated that the recombinant yeast was able to convert CIN into COU (conversion rate ranging from 2 to 5%) in all the organs of the rat's digestive tract: stomach, duodenum, jejunum, ileum, cecum, and colon. These results promise new opportunities for the development of drug delivery systems based on engineered yeasts catalyzing a bioconversion reaction directly in the digestive tract.


Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
Elizabeth N. Morgan ◽  
Edward M. Boyle ◽  
Wang Yun ◽  
John C. Kovacich ◽  
Timothy G. Canty ◽  
...  

Background —Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo. Methods and Results —The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean±SEM and compared by Student’s t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7±11% was necrotic in the animal treated with vehicle. In contrast, 20.9±7.0% was necrotic in the animals treated with PAF-AH ( P <0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion ( P <0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone. Conclusions —PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.


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