Inhaled cationic amphiphilic drug-induced pulmonary phospholipidosis in rats and dogs: time-course and dose–response of biomarkers of exposure and effect

Toxicology ◽  
2005 ◽  
Vol 207 (1) ◽  
pp. 59-72 ◽  
Author(s):  
Jürgen Pauluhn
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Drug Induced ◽  
Biomarkers Of Exposure ◽  
Amphiphilic Drug

Time course of insulin resistance associated with feeding dogs a high-fat diet

1997 ◽  
Vol 272 (1) ◽  
pp. E147-E154 ◽  
Author(s):  
A. P. Rocchini ◽  
P. Marker ◽  
T. Cervenka
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Glucose Uptake ◽  
Dose Response ◽  
High Fat Diet ◽  
Time Course ◽  
Rapid Development ◽  
Diet Group ◽  
Whole Body ◽  
High Fat

The current study evaluated both the time course of insulin resistance associated with feeding dogs a high-fat diet and the relationship between the development of insulin resistance and the increase in blood pressure that also occurs. Twelve adult mongrel dogs were chronically instrumented and randomly assigned to either a control diet group (n = 4) or a high-fat diet group (n = 8). Insulin resistance was assessed by a weekly, single-dose (2 mU.kg-1.min-1) euglycemic-hyperinsulinemic clamp on all dogs. Feeding dogs a high-fat diet was associated with a 3.7 +/- 0.5 kg increase in body weight, a 20 +/- 4 mmHg increase in mean blood pressure, a reduction in insulin-mediated glucose uptake [(in mumol-kg-1.min-1) decreasing from 72 +/- 6 before to 49 +/- 7 at 1 wk, 29 +/- 3 at 3 wk, and 30 +/- 2 at 6 wk of the high-fat diet, P < 0.01]. and a reduced insulin-mediated increase in cardiac output. In eight dogs (4 high fat and 4 control), the dose-response relationship of insulin-induced glucose uptake also was studied. The whole body glucose uptake dose-response curve was shifted to the right, and the rate of maximal whole body glucose uptake was significantly decreased (P < 0.001). Finally, we observed a direct relationship between the high-fat diet-induced weekly increase in mean arterial pressure and the degree to which insulin resistance developed. In summary, the current study documents that feeding dogs a high-fat diet causes the rapid development of insulin resistance that is the result of both a reduced sensitivity and a reduced responsiveness to insulin.

scholarly journals Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Elizabeth W Hunsaker ◽  
Chen-Hsin Albert Yu ◽  
Katherine J Franz
Keyword(s):  
Candida Albicans ◽  
Time Course ◽  
Transcriptional Response ◽  
Metal Homeostasis ◽  
Metal Availability ◽  
Drug Induced ◽  
Transcriptomic Response ◽  
Opportunistic Fungal Pathogen ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal homeostasis, we sought to address how the availability of copper in particular impacts the response of the opportunistic fungal pathogen Candida albicans to treatment with the antifungal drug fluconazole. The present study reports whole transcriptome analysis via time-course RNA-seq of C. albicans cells exposed to fluconazole with and without 10 µM supplemental CuSO4 added to the growth medium. The results show widespread impacts of small changes in Cu availability on the transcriptional response of C. albicans to fluconazole. Of the 2359 genes that were differentially expressed under conditions of cotreatment, 50% were found to be driven uniquely by exposure to both Cu and fluconazole. The breadth of metabolic processes that were affected by cotreatment illuminates a fundamental intersectionality between Cu metabolism and fungal response to drug stress. More generally, these results show that seemingly minor fluctuations in Cu availability are sufficient to shift cells’ transcriptional response to drug stress. Ultimately, the findings may inform the development of new strategies that capitalize on drug-induced vulnerabilities in metal homeostasis pathways.

rhIGF-I Enhances Functional Recovery from Sciatic Crush Time-Course and Dose-Response Study

1993 ◽  
Vol 692 (1 The Role of I) ◽  
pp. 314-316 ◽  
Author(s):  
PATRICIA C. CONTRERAS ◽  
CATHY STEFFLER ◽  
JEFFRY L. VAUGHT
Keyword(s):  
Functional Recovery ◽  
Dose Response ◽  
Time Course ◽  
Dose Response Study

scholarly journals Rat uterine microbiochemistry: metabolic enzyme activities stimulated by 17-beta-estradiol are localized in epithelial cells.

1987 ◽  
Vol 35 (6) ◽  
pp. 657-662 ◽  
Author(s):  
J P Holt ◽  
E Rhe
Keyword(s):  
Enzyme Activity ◽  
Smooth Muscle ◽  
Epithelial Cells ◽  
Dose Response ◽  
Enzyme Activities ◽  
Time Course ◽  
Citrate Synthase ◽  
Ovariectomized Rats ◽  
Similar Response ◽  
Estradiol Treatment

Lactate dehydrogenase (LDH; EC 1.1.1.27), citrate synthase (CS; EC 4.1.3.7), and beta-hydroxyacyl-CoA-dehydrogenase (beta-OH-acyl-CoA-DH; EC 1.1.1.35) activities were determined in each of the three major cell types of rat uterus, i.e., epithelial, stromal, and smooth muscle, using quantitative microanalytical techniques. Adult ovariectomized rats were treated with 17-beta-estradiol to determine the time course and dose response (0.025-50 micrograms/300-g rat) effect of estrogen on enzyme activity of each type of uterine cell. The use of "oil well" and enzyme-cycling microtechniques to determine the time course and the dose responses of enzyme activity changes required microassays involving 1595 microdissected single cell specimens. Estradiol treatment increased epithelial LDH, CS and beta-OH-acyl-CoA-DH activity but had no effect on these enzymes in the stroma or in smooth muscle cells. The estradiol-stimulated peak enzyme activities on Day 4 in the intervention group are compared with those in the ovariectomized rat controls as follows: LDH, 44.5 +/- 3.5 vs 22.3 +/- 3.9; CS, 3.5 +/- 0.2 vs 1.5 +/- 0.6; beta-OH-acyl-CoA-H, 3.5 +/- 0.32 vs 2.2 +/- 0.2 (mean +/- standard deviation; mol/kg/hr). Stromal cell activities (LDH, 7.4 +/- 1.0; CS, 1.2 +/- 0.2; beta-OH-acyl-CoA-DH, 0.9 +/- 0.1) were significantly lower than epithelial cell levels and were similar to smooth muscle levels. Therefore, even in the ovariectomized animal epithelial cells have markedly higher metabolic activity compared with adjacent cells. The enzyme activities are expressed as moles of substrate reacting per kilogram of dry weight per hour. All three enzymes exhibited a 17-beta-estradiol-induced dose response between 0.025-0.15 micrograms/300-g rat. The three enzymes studied all had similar response patterns to estrogen. The effect of estradiol was restricted to epithelial cells, with enzyme activities increasing to maximal levels after approximately 96 hr of hormone treatment. This study therefore not only confirms the specific and differential metabolic responses of uterine cells to estradiol treatment, but clearly demonstrates that marked metabolic differences exist between epithelial cells and stromal or smooth muscle uterine cells.

scholarly journals Validation study on urinary biomarkers of exposure for aflatoxin B1, ochratoxin A, fumonisin B1, deoxynivalenol and zearalenone in piglets

2013 ◽  
Vol 6 (3) ◽  
pp. 299-308 ◽  
Author(s):  
S. Gambacorta ◽  
H. Solfrizzo ◽  
A. Visconti ◽  
S. Powers ◽  
A.M. Cossalter ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Dose Response ◽  
Fumonisin B1 ◽  
Correlation Coefficients ◽  
Urinary Biomarkers ◽  
Post Dose ◽  
Toxigenic Fungi ◽  
Biomarkers Of Exposure ◽  
Commission Recommendation ◽  
Aflatoxin B

The multi-biomarker approach was used to validate urinary biomarkers in piglets administered boluses contaminated with mixtures of deoxynivalenol (DON), aflatoxin B1 (AFB1), fumonisin B1 (FB1), zearalenone (ZEA) and ochratoxin A (OTA) at different concentrations. Boluses contaminated with mycotoxins were prepared by slurrying and freezedrying feed material fortified with culture extracts of selected toxigenic fungi. Piglets were individually placed in metabolic cages to collect urine before gavage and 24 h post dose. Urine samples were hydrolysed with β-glucuronidase and analysed by a multi-biomarker LC-MS/MS method developed and validated to identify and measure biomarkers of FB1, OTA, DON, ZEA and AFB1. Urinary levels of FB1, OTA, DON + de-epoxy-deoxynivalenol, ZEA + alphazearalenol and aflatoxin M1 were selected as biomarkers of FB1, OTA, DON, ZEA and AFB1, respectively. Mean percentages of dietary mycotoxins excreted as biomarkers in 24 h post dose urine were 36.8% for ZEA, 28.5% for DON, 2.6% FB1, 2.6% for OTA and 2.5% for AFB1. A good correlation was observed between the amount of mycotoxins ingested and the amount of relevant biomarkers excreted in 24 h post dose urine. Linear dose-response correlation coefficients ranged between 0.68 and 0.78 for the tested couples of mycotoxin/biomarker. The good sensitivity of the LC-MS/MS method and the good dose-response correlations observed in this study permitted to validate the selected mycotoxin biomarkers in piglets at dietary levels close to the maximum permitted levels reported in Commission Directive 2003/100/EC for AFB1 and the guidance values reported in Commission Recommendation 2006/576/EC for DON, ZEA, OTA and FB1.

scholarly journals Gene selection and clustering for time-course and dose-response microarray experiments using order-restricted inference

2003 ◽  
Vol 19 (7) ◽  
pp. 834-841 ◽  
Author(s):  
S. D. Peddada ◽  
E. K. Lobenhofer ◽  
L. Li ◽  
C. A. Afshari ◽  
C. R. Weinberg ◽  
...  
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Gene Selection ◽  
Order Restricted Inference ◽  
Microarray Experiments ◽  
Order Restricted

Tolerance to self-administration of cocaine in rats: time course and dose-response determination using a multi-dose method

1993 ◽  
Vol 32 (3) ◽  
pp. 247-256 ◽  
Author(s):  
M.W. Emmett-Oglesby ◽  
R.L. Peltier ◽  
R.Y. Depoortere ◽  
C.L. Pickering ◽  
M.L. Hooper ◽  
...  
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Self Administration ◽  
Dose Method ◽  
Response Determination

scholarly journals Initial Inoculum and the Severity of COVID-19: A Mathematical Modeling Study of the Dose-Response of SARS-CoV-2 Infections

Epidemiologia ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 5-15
Author(s):  
Baylor Fain ◽  
Hana M. Dobrovolny
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Severe Disease ◽  
Equation Model ◽  
Viral Titer ◽  
Response Curves ◽  
Agent Based ◽  
Initial Inoculum ◽  
Peak Viral Load ◽  
Titer Curve

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes a variety of responses in those who contract the virus, ranging from asymptomatic infections to acute respiratory failure and death. While there are likely multiple mechanisms triggering severe disease, one potential cause of severe disease is the size of the initial inoculum. For other respiratory diseases, larger initial doses lead to more severe outcomes. We investigate whether there is a similar link for SARS-CoV-2 infections using the combination of an agent-based model (ABM) and a partial differential equation model (PDM). We use the model to examine the viral time course for different sizes of initial inocula, generating dose-response curves for peak viral load, time of viral peak, viral growth rate, infection duration, and area under the viral titer curve. We find that large initial inocula lead to short infections, but with higher viral titer peaks; and that smaller initial inocula lower the viral titer peak, but make the infection last longer.

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