Pharmacokinetics, tissue distribution, and excretion of FGF-21 following subcutaneous administration in rats

2018 ◽  
Vol 10 (7) ◽  
pp. 1061-1069 ◽  
Author(s):  
Yufei He ◽  
Yazhuo Li ◽  
Zihong Wei ◽  
Xingyan Zhang ◽  
Jing Gao ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Subcutaneous Administration

Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration

Life Sciences ◽  
1996 ◽  
Vol 58 (7) ◽  
pp. PL119-PL122 ◽  
Author(s):  
Lindsay B. Hough ◽  
Sandra M. Pearl ◽  
Stanley D. Glick
Keyword(s):  
Tissue Distribution ◽  
Subcutaneous Administration

scholarly journals Tissue distribution of emulsified γ-tocotrienol and its long-term biological effects after subcutaneous administration

2014 ◽  
Vol 13 (1) ◽  
pp. 66 ◽  
Author(s):  
Lili Deng ◽  
Ying Peng ◽  
Yu Wu ◽  
Meilin Yang ◽  
Yuedi Ding ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Biological Effects ◽  
Subcutaneous Administration

scholarly journals Vitamin K Tissue Distribution Is Modified by Large-Dose Warfarin and Menaquinone-4 Content of the Diet

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1800-1800
Author(s):  
Guylaine Ferland ◽  
Pierre Allaire ◽  
Bouchra Ouliass
Keyword(s):  
Adipose Tissue ◽  
Tissue Distribution ◽  
Large Dose ◽  
Subcutaneous Administration ◽  
Experimental Period ◽  
Group Differences ◽  
Funding Sources ◽  
Dose Warfarin ◽  
Male Wistar Rats ◽  
One Way Anova

Abstract Objectives Investigate the influence of large-dose warfarin (W) on tissue K1 and MK-4 distribution in rats fed a standard K1 diet, or enriched with MK4. Methods Male Wistar rats were fed a regular K1 (750 mcg K1/kg/diet; WK1) or enriched MK-4 (100 mg MK-4/kg/diet; WK1 + MK4) diet for 1 week after which they were administered 14 mg W/kg/day (in drinking water) and subcutaneous K1 (94 mg/kg, 3X/week; to maintain coagulation), for 12 weeks; diets were maintained throughout the experimental period. Respective diet controls (C and C + MK4) received subcutaneous saline and regular water. K1 and M-4 quinone and their epoxide forms (K1O and MK-4O) were assessed in serum, liver, heart, kidney, pancreas, adipose tissue and brain, by HPLC. Group differences were tested by one-way ANOVA, and by t-test for each K vitamer. Results In C group, K1 was the predominant K vitamer in serum, liver and heart, whereas MK-4 was found in relative higher concentrations in kidney, pancreas, brain, and adipose tissue. In MK-4 containing organs, W treatment was associated with significantly lower MK-4 concentration in pancreas, brain, and heart (P < 0.05) despite the local presence of K1, which suggests that W may block the production of MK-4 by UBIAD1. Compared to C group, K1 concentrations were significantly higher in all organs and serum in WK1 and WK1 + MK4 groups as a result of the subcutaneous administration. Interestingly, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), K1 concentrations in naturally K1 rich tissues (i.e., liver, heart and serum) were significantly increased when compared to those from the WK1 group (P < 0.05), suggesting that dietary MK-4 may play a role in modulating the uptake of K1 in these tissues. Except in liver, W administration (WK1 and WK1 + MK4) was associated with higher tissue concentrations of K1 and MK-4 epoxide when compared to C group (P < 0.05). Noteworthy, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), naturally rich MK-4 containing organs (i.e., kidney, pancreas, adipose tissue and brain) presented significantly higher concentration of MK-4 epoxide (relative to K1 epoxide), suggesting a preferential use of MK4 by these organs when available from the diet. Conclusions In conclusion, results from this study point to modulatory roles of W and dietary MK-4 on tissue distribution of K1 and MK-4 in what appears to be a tissue specific manner. Funding Sources CIHR.

scholarly journals High monocyte to lymphocyte ratio is associated with impaired protection after subcutaneous administration of BCG in a mouse model of tuberculosis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 296
Author(s):  
Andrea Zelmer ◽  
Lisa Stockdale ◽  
Satria A. Prabowo ◽  
Felipe Cia ◽  
Natasha Spink ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tissue Distribution ◽  
Inbred Mouse ◽  
Subcutaneous Administration ◽  
Mouse Strains ◽  
Human Populations ◽  
Early Assessment ◽  
Vaccine Candidates ◽  
Immunological Mechanisms ◽  
Tissue Homogenates

Background:The only available tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy. New vaccines are therefore urgently needed. Why BCG fails is incompletely understood, and the tools used for early assessment of new vaccine candidates do not account for BCG variability. Taking correlates of risk of TB disease observed in human studies and back-translating them into mice to create models of BCG variability should allow novel vaccine candidates to be tested early in animal models that are more representative of the human populations most at risk. Furthermore, this could help to elucidate the immunological mechanisms leading to BCG failure. We have chosen the monocyte to lymphocyte (ML) ratio as a correlate of risk of TB disease and have back-translated this into a mouse model.Methods: Four commercially available, inbred mouse strains were chosen. We investigated their baseline ML ratio by flow cytometry; extent of BCG-mediated protection from Mycobacterium tuberculosisinfection by experimental challenge; vaccine-induced interferon gamma (IFNγ) response by ELISPOT assay; and tissue distribution of BCG by plating tissue homogenates.Results:The ML ratio varied significantly between A/J, DBA/2, C57Bl/6 and 129S2 mice. A/J mice showed the highest BCG-mediated protection and lowest ML ratio, while 129S2 mice showed the lowest protection and higher ML ratio. We also found that A/J mice had a lower antigen specific IFNγ response than 129S2 mice. BCG tissue distribution appeared higher in A/J mice, although this was not statistically significant.Conclusions:These results suggest that the ML ratio has an impact on BCG-mediated protection in mice, in alignment with observations from clinical studies. A/J and 129S2 mice may therefore be useful models of BCG vaccine variability for early TB vaccine testing. We speculate that failure of BCG to protect from TB disease is linked to poor tissue distribution in a ML high immune environment.

scholarly journals High monocyte to lymphocyte ratio is associated with impaired protection after subcutaneous administration of BCG in a mouse model of tuberculosis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 296 ◽  
Author(s):  
Andrea Zelmer ◽  
Lisa Stockdale ◽  
Satria A. Prabowo ◽  
Felipe Cia ◽  
Natasha Spink ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tissue Distribution ◽  
Inbred Mouse ◽  
Subcutaneous Administration ◽  
Mouse Strains ◽  
Human Populations ◽  
Early Assessment ◽  
Vaccine Candidates ◽  
Immunological Mechanisms ◽  
Tissue Homogenates

Background: The only available tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy. New vaccines are therefore urgently needed. Why BCG fails is incompletely understood, and the tools used for early assessment of new vaccine candidates do not account for BCG variability. Taking correlates of risk of TB disease observed in human studies and back-translating them into mice to create models of BCG variability should allow novel vaccine candidates to be tested early in animal models that are more representative of the human populations most at risk. Furthermore, this could help to elucidate the immunological mechanisms leading to BCG failure. We have chosen the monocyte to lymphocyte (ML) ratio as a correlate of risk of TB disease and have back-translated this into a mouse model. Methods: Four commercially available, inbred mouse strains were chosen. We investigated their baseline ML ratio by flow cytometry; extent of BCG-mediated protection from Mtb infection by experimental challenge; vaccine-induced interferon gamma (IFNγ) response by ELISPOT assay; and tissue distribution of BCG by plating tissue homogenates. Results: The ML ratio varied significantly between A/J, DBA/2, C57Bl/6 and 129S2 mice. A/J mice showed the highest BCG-mediated protection and lowest ML ratio, while 129S2 mice showed the lowest protection and higher ML ratio. We also found that A/J mice had a lower antigen specific IFNγ response than 129S2 mice. BCG tissue distribution appeared higher in A/J mice, although this was not statistically significant. Conclusions: These results suggest that the ML ratio has an impact on BCG-mediated protection in mice, in alignment with observations from clinical studies. A/J and 129S2 mice may therefore be useful models of BCG vaccine variability for early TB vaccine testing. We speculate that failure of BCG to protect from TB disease is linked to poor tissue distribution in a ML high immune environment.

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