scholarly journals Bugs and drugs: a systems biology approach to characterising the effect of moxidectin on the horse’s faecal microbiome

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
S. P. Daniels ◽  
J. Leng ◽  
J. R. Swann ◽  
C. J. Proudman
Keyword(s):  
Gut Microbiota ◽  
Treated Group ◽  
Anthelmintic Treatment ◽  
Metabolic Profiles ◽  
Faecal Microbiota ◽  
Treatment Groups ◽  
Fermentation Kinetics ◽  
And Control

Abstract Background Anthelmintic treatment is a risk factor for intestinal disease in the horse, known as colic. However the mechanisms involved in the onset of disease post anthelmintic treatment are unknown. The interaction between anthelmintic drugs and the gut microbiota may be associated with this observed increase in risk of colic. Little is known about the interaction between gut microbiota and anthelmintics and how treatment may alter microbiome function. The objectives of this study were: To characterise (1) faecal microbiota, (2) feed fermentation kinetics in vitro and (3) metabolic profiles following moxidectin administration to horses with very low (0 epg) adult strongyle burdens. Hypothesis: Moxidectin will not alter (1) faecal microbiota, (2) feed fermentation in vitro, or, (3) host metabolome. Results Moxidectin increased the relative abundance of Deferribacter spp. and Spirochaetes spp. observed after 160 h in moxidectin treated horses. Reduced in vitro fibre fermentation was observed 16 h following moxidectin administration in vivo (P = 0.001), along with lower pH in the in vitro fermentations from the moxidectin treated group. Metabolic profiles from urine samples did not differ between the treatment groups. However metabolic profiles from in vitro fermentations differed between moxidectin and control groups 16 h after treatment (R2 = 0.69, Q2Y = 0.48), and within the moxidectin group between 16 h and 160 h post moxidectin treatment (R2 = 0.79, Q2Y = 0.77). Metabolic profiles from in vitro fermentations and fermentation kinetics both indicated altered carbohydrate metabolism following in vivo treatment with moxidectin. Conclusions These data suggest that in horses with low parasite burdens moxidectin had a small but measurable effect on both the community structure and the function of the gut microbiome.

A Novel Interleukin-IL-6 (IL-6) Dependent Syngeneic Multiple Myeloma (MM) Model in SCID Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4891-4891
Author(s):  
Mohamed H. Zaki ◽  
Zhao Zhou ◽  
Francis L. McCabe ◽  
Hillary J. Millar ◽  
Christine McCauley ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Volume ◽  
Plasma Cells ◽  
Treated Group ◽  
Scid Mice ◽  
Tumor Bearing ◽  
The Mean ◽  
And Control

Abstract IL-6 is a multifunctional cytokine that is implicated in the pathophysiology of several malignant diseases including MM, an incurable malignant plasma cell disorder. IL-6 is known to enhance proliferation, differentiation and survival of malignant plasma cells in MM through an autocrine and/or a paracrine mechanism that involves the inhibition of apoptosis of the malignant cells, induction of resistance to chemotherapy and contribution to angiogenesis. Moreover, elevated levels of IL-6 in serum of patients with MM correlate with disease activity, unfavorable prognosis and refractoriness to standard therapy. Blocking IL-6 has been postulated to be an effective therapy (Klein et al, 1995) and several studies have investigated the effect of blocking IL-6 on MM cells and cell lines both in vitro and in vivo. However, the lack of a reliable IL-6 dependent MM model has hindered these efforts. Recently, mouse plasmacytomas were described as appropriate models to study the biology of human MM (Iankov et al., Immunobiology2004; 208(5)). The current study describes a new in vivo IL-6 dependent mouse plasmacytoma model in SCID mice. Mice were inoculated subcutaneously with 1 x 106 7TD1 cells, an IL-6 dependent mouse hybridoma/plasmacytoma cell line. Three days after tumor inoculation, mice were treated 2x/week i.p. with either PBS or 25 mg/kg of anti-mouse IL-6 (R & D systems, Clone MP520F3) or control mAb. Thirteen days after tumor implantation the mean tumor volume in the control mAb group and PBS group was 3204 +/− 360 SEM mm3, n = 10; and 2430 +/− 189 SEM mm3, n = 10, respectively. The mean tumor volume in the anti-IL-6 treated group was 635 +/− 149 SEM mm3, n = 10. Serum was tested by ELISA for levels of IL-6 and IgM (a mAb that is produced by 7TD1 cell line). IL-6 serum level was undetectable in naïve non-tumor bearing SCID mice. The IL-6 levels in the PBS treated group and control mAb group were 121 +/− 32 pg/ml and 125 +/− 14 pg/ml, respectively. IL-6 levels in animals treated with rat-anti- mouse IL-6 were not detected due to interference of the mAb with the ELISA. Serum IgM levels in optical density (OD) were 0.02 +/− 0.005 in the naïve non-tumor bearing animals, 0.80 +/− 0.02 in the PBS group, 0.77 +/− 0.03, in the control mAb group, and 0.19 +/− 0.17 in the rat anti-mouse IL-6 group. In conclusion the current study showed that 7TD1cells could be grown in SCID mice. Serum levels of both IgM and IL-6 were significantly elevated in the PBS and control mAb treated tumor-bearing animals. There was a significant reduction in the IgM levels in the rat anti-mouse IL-6 treated group (P <0.0001), a positive correlation between final tumor weight and serum IgM level (P < 0.0001, r2 = 0.782) and a 74% inhibition of tumor growth relative to either control mAb or vehicle control (P <0.0001). Taken together the current study introduces a new IL-6 dependant mouse plasmacytoma model that can be used to study the biology of MM and to test the efficacy of IL-6 blocking agents in vivo.

scholarly journals Preliminary screening of the possible protective effect of Moroccan propolis against chromium-induced nephrotoxicity in animal model

2020 ◽  
Vol 13 (7) ◽  
pp. 1327-1333
Author(s):  
Soukaina El-Guendouz ◽  
Soumia Zizi ◽  
Youssef Elamine ◽  
Badiaa Lyoussi
Keyword(s):  
Animal Model ◽  
Protective Effect ◽  
Creatinine Clearance ◽  
Potassium Dichromate ◽  
Treated Group ◽  
Control Groups ◽  
Before And After ◽  
And Control

Background and Aim: Hexavalent chromium (Cr (VI)) compounds have been shown to induce nephrotoxicity associated with oxidative stress in humans and animals. The aim of the present study was to investigate the nephroprotective effect of bee propolis, as highly antioxidant natural product, in vivo using an animal model. Materials and Methods: First of all, total phenol and flavonoid contents of propolis sample were estimated in vitro. Afterward, to study the protective effect of propolis on renal damages caused by an injection of a single dose of potassium dichromate (15 mg/kg b.wt), 24 male Wister rats were divided into test and control groups. Propolis treatment was performed by oral gavage of 100 mg/kg b.wt/day, while the control groups received water instead. The 24 h urine was collected and blood samples were withdrawn before and after each treatment for further analysis. Results: Propolis revealed to be rich in polyphenols and flavonoids. Chromate provoked a nephrotoxic effect expressed by a drastic decrease in glomerular filtration assessed by creatinine clearance. However, the administration of propolis attenuated the renal damages induced by the chromate. This attenuation can be seen by the increase of creatinine clearance when comparing propolis treated group to the non-treated group. Conclusion: Propolis showed a protective potential against chromate-induced nephrotoxicity through the amelioration of chromate's toxic effects. It might be concluded that propolis could be effective as chemoprotectant in the management of potassium dichromate-induced nephrotoxicity.

Effects of different sources and levels of tannins on live performance and antioxidant response of Ossimi lambs

2020 ◽  
Vol 158 (4) ◽  
pp. 339-348
Author(s):  
Tamer M. M. Hassan ◽  
Omar A. Ahmed-Farid ◽  
Fathy A. I. Abdel-Fattah
Keyword(s):  
Control Diet ◽  
Protein Digestibility ◽  
Antioxidant Response ◽  
Live Performance ◽  
Treatment Groups ◽  
Stress Markers ◽  
Mango Leaves ◽  
And Control

AbstractPomegranate peels (PP) and mango leaves (ML) were analysed for nutrients and tannin contents. In an in vitro test, ten diets were prepared; six contained 2, 4 and 6% of PP or ML, three diets supplemented with mixed levels of PP and ML (1 + 1%, 2 + 2% and 3 + 3%) and control diet free of them. Gas was measured after 3, 6, 12, 24, 48 and 72 h of incubation. Methane and rumen parameters were estimated. In an in vivo experiment, 40 Ossimi lambs were divided into four groups; the first was control, other groups (T1, T2 and T3) fed diets containing 6% PP, 6% ML or mix levels (3% PP + 3%ML), respectively, for 2 months. Results showed that PP and ML were rich in tannins. In the in vitro test, a maximum reduction in gas, methane and NH3-N was in 6% PP, 6% ML and mixed levels (3% PP + 3% ML). In the in vivo experiment, there were no differences in growth and digestibility of DM and nutrients between treatment groups. Only a lowered DM intake and protein digestibility in lambs fed 6% PP. Gas and methane emission was decreased significantly in lambs fed 6% PP, compared to other groups. TVFAs and NH3-N were decreased for treatment groups. Also, all treatments did not show any pathological changes in liver function or on oxidative stress markers. In conclusion, PP and ML can be used in sheep diets at inclusion levels of 6% and mixture without detrimental effects on general health of Ossimi lambs.

scholarly journals Birth of lambs of a pre-determined sex after in vitro production of embryos using frozen–thawed sex-sorted and re-frozen–thawed ram spermatozoa

Reproduction ◽  
2004 ◽  
Vol 127 (5) ◽  
pp. 557-568 ◽  
Author(s):  
F K Hollinshead ◽  
G Evans ◽  
K M Evans ◽  
S L Catt ◽  
W M C Maxwell ◽  
...  
Keyword(s):  
High Speed ◽  
Gradient Centrifugation ◽  
In Vitro Production ◽  
Blastocyst Development ◽  
Embryo Survival ◽  
Treatment Groups ◽  
Sperm Migration ◽  
And Control

The characteristics and functional capacity of ram spermatozoa frozen–thawed prior to and after flow cytometric sorting was assessed after incubation (37 °C; 6 h),in vitrofertilisation (IVF), and transfer of fresh and vitrifiedin vitroproduced embryos. Frozen-thawed spermatozoa from two rams were allocated to four treatment groups: (i) non-sorted (Control); (ii) sorted (FS); (iii) sorted then re-frozen (FSF) and (iv) re-frozen control (FCF). Frozen-thawed samples were separated into X- and Y-chromosome bearing spermatozoa using a high-speed sperm sorter after density gradient centrifugation (X: 88 ± 1.5% and Y: 87 ± 1.1% purity). After 6 h incubation (37 °C), the percentage of motile spermatozoa was higher (P< 0.001) for FS (84 ± 2.0%) compared with all other treatments (Control: 36 ± 3.3%, FSF: 28 ± 3.1%, FCF: 20 ± 2.0%). In a sperm migration test greater numbers of FS spermatozoa penetrated 5 mm into the artificial cervical mucus compared with spermatozoa from all other treatments (152 ± 39.4 vs 31 ± 9.2 spermatozoa respectively;P< 0.05). Fertilisation and cleavage rates were higher (P< 0.05) forin vitromatured oocytes inseminated with Control compared with FSF spermatozoa. However, the Day 7 blastocyst development rate was higher for oocytes inseminated with FSF (62.2%) than FS and Control spermatozoa (52.7 and 50.0%;P< 0.05). The number of ewes pregnant (Day 60), lambing and thein vivoembryo survival rate was greater (P< 0.01) after the transfer of fresh embryos rather than vitrified embryos derived from X- and Y-spermatozoa (67.6, 64.7 and 41.2% vs 29.6, 25.9 and 14.8% respectively). Twenty-six of the 30 (86.7%) lambs derived from sex-sorted spermatozoa were of the correct sex. These results demonstrate that frozen–thawed ram spermatozoa can be sex-sorted for immediate or future use after re-cryopreservation and, in conjunction with IVF and embryo transfer, can be used to efficiently produce offspring of pre-determined sex.

Apelin-13 deteriorates hypertension in rats after damage of the vascular endothelium by ADMA

2013 ◽  
Vol 91 (9) ◽  
pp. 708-714 ◽  
Author(s):  
Xue Han ◽  
Dong-Liang Zhang ◽  
Dao-Xin Yin ◽  
Qi-Dong Zhang ◽  
Wen-Hu Liu
Keyword(s):  
Endothelial Dysfunction ◽  
Treated Group ◽  
Control Group ◽  
Transmission Electron ◽  
Before And After ◽  
Pass Through ◽  
Mlc Phosphorylation ◽  
And Control

Asymmetric dimethylarginine (ADMA) is a risk factor for endothelial dysfunction. The polypeptide apelin has biphasic effects on blood vessels in vivo and in vitro. We investigated the effect of apelin-13 on ADMA-damaged vessels. Rats were divided among ADMA-treated and control groups, which were treated with ADMA (10 mg·(kg body mass)−1·day−1) or saline, respectively, for 4 weeks. Systolic blood pressure (SBP) was measured before and after the injection of apelin-13. The ultrastructure of endothelial cells in caudal arteries was examined using transmission electron microscopy. The reactivities of isolated caudal artery rings were observed after exposure to apelin-13, and myosin light chain (MLC) phosphorylation was assessed by immunohistochemistry in rings treated with or without apelin-13. ADMA induced hypertension and endothelial dysfunction. After injection of apelin-13, SBP declined in the control group but was elevated in the ADMA-treated group. In vitro, apelin-13 caused relaxation in rings in the control group, but it contracted rings in the ADMA-treated group. Apelin-13 promoted MLC phosphorylation in vascular smooth muscle cells (VSMCs) in the ADMA group. These results indicate that apelin-13 might pass through ADMA-damaged endothelium and act on VSMCs to increase MLC phosphorylation, thus contributing to vasoconstriction and exacerbating hypertension.

Plant polyphenols alter a pathway of energy metabolism by inhibiting fecal Bacteroidetes and Firmicutes in vitro

2016 ◽  
Vol 7 (3) ◽  
pp. 1501-1507 ◽  
Author(s):  
Bin Xue ◽  
Jinli Xie ◽  
Jiachen Huang ◽  
Long Chen ◽  
Lijuan Gao ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Gut Microbiota ◽  
Microbiota Composition ◽  
Faecal Microbiota ◽  
Plant Polyphenols ◽  
Gut Microbiota Composition

This study investigated the effect of plant polyphenols on faecal microbiota metabolizing oligosaccharides. The results show that plant polyphenols can change the pathway of degrading FOS or even energy metabolism in vivo by altering gut microbiota composition.

scholarly journals HumanClostridium difficileinfection: inhibition of NHE3 and microbiota profile

2015 ◽  
Vol 308 (6) ◽  
pp. G497-G509 ◽  
Author(s):  
Melinda A. Engevik ◽  
Kristen A. Engevik ◽  
Mary Beth Yacyshyn ◽  
Jiang Wang ◽  
Daniel J. Hassett ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Financial Burden ◽  
Toxin B ◽  
Intestinal Environment ◽  
Mrna And Protein Expression ◽  
Stool Microbiota ◽  
Hospital Acquired ◽  
And Control

Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na+/H+exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na+and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na+and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile.

Evaluation of the Effect of Epilobium angustifolium Aqueous Extract on LNCaP Cell Proliferation in In Vitro and In Vivo Models

Planta Medica ◽  
2017 ◽  
Vol 83 (14/15) ◽  
pp. 1159-1168 ◽  
Author(s):  
Jakub Piwowarski ◽  
Barbara Bobrowska-Korczak ◽  
Iwona Stanisławska ◽  
Wojciech Bielecki ◽  
Robert Wrzesien ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Aqueous Extract ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Lncap Cells ◽  
In Vivo Models ◽  
Epilobium Angustifolium ◽  
Oenothein B

Abstract Epilobium sp. are commonly used in traditional medicine in the treatment of early stages of benign prostatic hyperplasia and inflammation. It is suggested that a dominating constituent, oenothein B, is responsible for the extracts therapeutic effects. Several bioactivities were established for extracts and oenothein B in various in vitro models, but due to the questionable bioavailability of this dimeric macrocyclic ellagitannin, their significance in the in vivo effects remains unresolved. We have thus focused our attention on a complex comparative investigation of the in vitro and in vivo activities of phytochemically characterized Epilobium angustifolium aqueous extract and oenothein B on prostate cancer cells proliferation.Incubation of different cell lines with E. angustifolium aqueous extract resulted in a significant reduction of proliferation of PZ-HPV-7 and LNCaP cells, which was partly associated with antiandrogenic activity. These effects were fully congruent with oenothein B, examined in parallel. Oral supplementation of rats implanted with LNCaP cells with E. angustifolium aqueous extract 50–200 mg/kg b. w. resulted in a reduction of the occurrence of prostatic adenoma up to 13 %. Oenothein B was not detected in the urine and feces of the E. angustifolium aqueous extract-treated group, however, conjugates of nasutins gut microbiota metabolites of ellagitannins were detected in the urine, while in human volunteers supplemented with Epilobium tea, only urolithin conjugates were present.Despite observing significant and consistent effects in vitro and in vivo, we were unable to point out unequivocally the factors contributing to the observed E. angustifolium aqueous extract activity, facing the problems of an unknown metabolic fate of oenothein B and interspecies differences in E. angustifolium aqueous extract gut microbiota metabolism.

scholarly journals 1368. Assessment of the In Vivo Efficacy of Human-Simulated Epithelial Lining Fluid (ELF) Exposure of Meropenem/Nacubactam (MEM/NAC) Combination Against β-Lactamase-Producing Enterobacteriaceae in Neutropenic Lung Infection Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S419-S419 ◽  
Author(s):  
Tomefa E Asempa ◽  
Ana Motos ◽  
Kamilia Abdelraouf ◽  
Caterina Bissantz ◽  
Claudia Zampaloni ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Lung Infection ◽  
Infection Model ◽  
Bacterial Reduction ◽  
Treatment Groups ◽  
Class D ◽  
Dual Action ◽  
And Control

Abstract Background NAC is a novel dual action β-lactamase inhibitor with in vitro activity against class A, class C, and some class D β-lactamases and antibacterial activity against Enterobactaeriaceae. NAC is being developed as a combination therapy with MEM for the treatment of serious Gram-negative bacterial infections. This study evaluated the efficacy of the human-simulated ELF exposure of MEM/NAC, compared with those of MEM or NAC alone against β-lactamase-producing Enterobacteriaceae isolates in the neutropenic murine lung infection model. Methods Eight clinical MEM-resistant Enterobacteriaceae isolates harboring various β-lactamases (IMI, KPC, OXA, TEM, SHV, and AmpC) were utilized in the study. MEM and MEM:NAC (1:1) combination MICs were determined in triplicate via broth microdilution. ICR mice were rendered transiently neutropenic, and lungs were inoculated with 50 µL bacterial suspensions of 107 CFU/mL. Regimens in mice that simulated the human ELF exposures following doses of MEM 2g q8h and NAC 2g q8h (1.5 hours infusions) as monotherapies and in combination were established. Treatment mice received MEM human-simulated regimen (HSR), NAC HSR, or MEM/NAC HSR and control mice were vehicle-dosed. Treatment was started 2 hours after inoculation and continued for 24 hours. Efficacy was assessed as the change in log10CFU/lung at 24 hours compared with 0 hours controls. Results MEM and MEM/NAC MICs were 8–512 and 0.5–8 mg/L, respectively. The average log10CFU/lung at 0 hours across all isolates was 6.26 ± 0.26. Relative to 0 hours control, the mean bacterial growth at 24 hours in the untreated control mice, MEM HSR, and NAC HSR treatment groups were 2.93 ± 0.29, 2.72 ± 0.42, and 1.75 ± 0.80 log10CFU/lung, respectively. MEM/NAC HSR resulted in up to 2-log bacterial reduction in isolates with MEM/NAC MIC ≤4 mg/L. Conclusion MEM/NAC human-simulated ELF exposure produced enhanced efficacy against MEM-resistant β-lactamase-producing Enterobacteriaceae isolates with MEM/NAC MIC ≤4 mg/L. These data support a potential role for MEM/NAC for treatment of lung infections due to β-lactamase-producing Enterobacteriaceae and warrant further studies. This project has been funded in part under HHS BARDA Contract HHSO100201600038C. Disclosures C. Bissantz, F Hoffmann La Roche Ltd.: Employee, Salary. C. Zampaloni, F. Hoffmann-La Roche Ltd.: Employee, Salary. D. P. Nicolau, Hoffmann-La Roche Ltd.: Grant Investigator, Grant recipient.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

Sign in / Sign up

Export Citation Format

Share Document