scholarly journals The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus

2005 ◽  
Vol 94 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Christopher A. Maloney ◽  
Christina Lilley ◽  
Morven Cruickshank ◽  
Caroline McKinnon ◽  
Susan M. Hay ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Kinase Inhibitors ◽  
Fetal Liver ◽  
Growth Arrest ◽  
Total Body Weight ◽  
Low Protein ◽  
Liver And Kidney ◽  
Steady State Levels ◽  
Total Body

During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet. In contrast, the ratio of fetal liver weight to total body weight is unchanged. To investigate the mechanisms underlying this disproportionate change in organ growth in the low-protein group, cell proliferation and differentiation have been assessed in the liver and kidney. The steady-state levels of mRNA for the growth-arrest and DNA-damage genegadd153/CHOP-10, CCAAT enhancer-binding proteins α and β were unaffected by maternal diet in both fetal liver and kidney. The mRNA for alpha-fetoprotein, albumin and hepatic glucokinase were unchanged in the liver, suggesting that maternal protein deficiency does not alter the state of differentiation. The steady-state levels of the mRNA coding for the cyclin-dependent protein kinase inhibitors (p15INK4a, p19INK4d, p21CIP1, p27KIP1and p57KIP2) were unchanged in the fetal livers but were significantly increased in the kidneys of fetuses from dams fed the low-protein diet. These results show that the asymmetrical growth of the kidney is associated with increases in mRNA for the Cip/Kip cyclin-dependent kinase inhibitors and that these may reflect specific lesions in organ development.

scholarly journals Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

2022 ◽  
Vol 25 ◽  
pp. 41-68
Author(s):  
Dion Brocks ◽  
Hamdah Al Nebaihi ◽  
Shamima Parvin ◽  
Amel Hamza
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Drug Clearance ◽  
Lean Body Weight ◽  
Adult Obesity ◽  
Metabolizing Enzymes ◽  
Comparative Pharmacokinetic ◽  
Liver And Kidney ◽  
Obese Subjects ◽  
Total Body

In many comparative trials examining the effects of adult obesity on pharmacokinetics of drugs, conclusions were made based on values that were either not adjusted to total body weight or adjusted to non-obese body mass (e.g., ideal or lean body weight). In many cases these values were higher in the obese subjects. We have reviewed the data from comparative human trials, and it is apparent that in examining clearance normalization to total body weight (as typically done in studies involving pediatric obese patients), the clearances are often reduced in the obese. We have also reviewed the results of experimental obese versus non-obese rodent models. Those studies have mostly found that the systemic exposures to the same dose per body weight are increased, with obesity-related decreases in clearance. Furthermore, the expression of a number of important drug metabolizing enzymes are reduced in the experimental obese state. There is also evidence that obesity causes increases in the measured mass of eliminating organs such as liver and kidney. Human clearance normalized to total body weight appears to better reflect the underlying changes reported in the expression of protein and functional activity of drug clearance mechanisms.  

scholarly journals Lean body weight versus total body weight to calculate the iodinated contrast media volume in abdominal CT: a randomised controlled trial

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Moreno Zanardo ◽  
Fabio Martino Doniselli ◽  
Anastassia Esseridou ◽  
Massimiliano Agrò ◽  
Nicol Antonina Rita Panarisi ◽  
...  
Keyword(s):  
Body Weight ◽  
Contrast Media ◽  
Controlled Trial ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Iodinated Contrast Media ◽  
Abdominal Ct ◽  
Iodinated Contrast ◽  
Significant Difference ◽  
Total Body

Abstract Objectives Iodinated contrast media (ICM) could be more appropriately dosed on patient lean body weight (LBW) than on total body weight (TBW). Methods After Ethics Committee approval, trial registration NCT03384979, patients aged ≥ 18 years scheduled for multiphasic abdominal CT were randomised for ICM dose to LBW group (0.63 gI/kg of LBW) or TBW group (0.44 gI/kg of TBW). Abdominal 64-row CT was performed using 120 kVp, 100–200 mAs, rotation time 0.5 s, pitch 1, Iopamidol (370 mgI/mL), and flow rate 3 mL/s. Levene, Mann–Whitney U, and χ2 tests were used. The primary endpoint was liver contrast enhancement (LCE). Results Of 335 enrolled patients, 17 were screening failures; 44 dropped out after randomisation; 274 patients were analysed (133 LBW group, 141 TBW group). The median age of LBW group (66 years) was slightly lower than that of TBW group (70 years). Although the median ICM-injected volume was comparable between groups, its variability was larger in the former (interquartile range 27 mL versus 21 mL, p = 0.01). The same was for unenhanced liver density (IQR 10 versus 7 HU) (p = 0.02). Median LCE was 40 (35–46) HU in the LBW group and 40 (35–44) HU in the TBW group, without significant difference for median (p = 0.41) and variability (p = 0.23). Suboptimal LCE (< 40 HU) was found in 64/133 (48%) patients in the LBW group and 69/141 (49%) in the TBW group, but no examination needed repeating. Conclusions The calculation of the ICM volume to be administered for abdominal CT based on the LBW does not imply a more consistent LCE.

Increases in adipose and total body weight, but not in lean body mass, associated with subcutaneous administration of Sonic hedgehog-Ig fusion protein to mice

2002 ◽  
Vol 57 (3) ◽  
pp. 107-114 ◽  
Author(s):  
Pauline L. Martin ◽  
Joan Lane ◽  
Louise Pouliot ◽  
Malcolm Gains ◽  
Rudolph Stejskal ◽  
...  
Keyword(s):  
Body Weight ◽  
Fusion Protein ◽  
Lean Body Mass ◽  
Body Mass ◽  
Sonic Hedgehog ◽  
Subcutaneous Administration ◽  
Total Body Weight ◽  
Total Body

Effects of the teratogenic folic acid antagonist, 9-methyl pteroylglutamic acid, on hydroxyproline levels in fetal rat limbs

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 289-294
Author(s):  
R. R. Schmidt ◽  
K. P. Chepenik ◽  
B. V. Paynton
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Total Body Weight ◽  
Pregnant Rats ◽  
Skeletal Malformations ◽  
Fetal Rat ◽  
Pteroylglutamic Acid ◽  
Limb Malformations ◽  
Total Body ◽  
Rate Of Accumulation

Pregnant rats were subjected to either a folic-acid-deficient regimen that produces multiple congenital skeletal malformations, or a control folic-acid-supplemented regimen. Fetal limbs were extirpated on days 16 and 18 of gestation, pooled from each litter, homogenized, and aliquots set aside for hydroxyproline, protein and DNA determinations. We found that (1) the amount of protein recovered per treated limb was approximately half that of controls on both days, (2) the amount of protein recovered per treated or controlday-18 limb was twice that of a day-16 limb, (3) treated limbs constituted the same percentage of total body weight as in controls on day 16, but a smaller percentage than in controls on day 18, and (4) the concentration of hydroxyproline (μg/mg protein) was significantly less for treated limbs than for controls on day 18 of gestation. We noted also that: (1) lowest hydroxyproline concentrations were found in limbs from treated fetuses with gross limb malformations, (2) intermediate concentrations were found in limbs of treated fetuses not exhibiting gross limb malformations, and (3) highest concentrations were found in control limbs. We suggest that the treatment resulted in (1) a decreased rate of accumulation of protein in limbs prior to day 16, but not from day 16 to day 18, (2) a decreased rate of accumulation of some non-protein component(s) in treated limbs from day 16 to day 18, and (3) an altered collagen metabolism.

scholarly journals Growth and body weight of free-range reindeer in western Alaska

Rangifer ◽  
2000 ◽  
Vol 20 (2-3) ◽  
pp. 221 ◽  
Author(s):  
Greg L. Finstad ◽  
Alexander K. Prichard
Keyword(s):  
Body Weight ◽  
Growth Rates ◽  
Total Body Weight ◽  
Growth Patterns ◽  
Spatial And Temporal Variation ◽  
Adult Males ◽  
Body Weights ◽  
Total Body ◽  
Reproductive Females ◽  
Average Body

Total body weight of 9749 reindeer calves and 4798 adult reindeer were measured from 1984 to 1999 on the Seward Peninsula, western Alaska, USA. Growth rates of male and female calves, and annual growth patterns of adults were determined. Male calves grew faster than female calves. Reproductive females were lighter than non-reproductive females during summer but there was no effect of reproduction on average body weights the following winter. Adult males age 3-5 were heavier during summer than winter. Castrated males weighed the same as uncastrated males in summer, but were significantly heavier in winter, and did not display the large annual fluctuations in weight typical of reproductive males and females. Growth rates were higher and body weights greater in this herd than many other cir-cumpolar reindeer populations. We suggest these kinds of physiological indices should be used to monitor the possible effects of spatial and temporal variation in population density and to evaluate changes in herding practices.

scholarly journals SUN-543 Real World Evidence of Successful Weight Management for the Obese Population: Complete Reversal of Obesity Related Metabolic Co-Morbidities and Weight Loss in Patients Attending a Multidisciplinary Weight Management Clinic in Australia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zoe Rock ◽  
Juliana Chen ◽  
Joanna Jaques ◽  
Bernard L Champion ◽  
Reginald V Lord ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Management ◽  
Exercise Physiology ◽  
Body Weight Loss ◽  
Total Body Weight ◽  
Management Interventions ◽  
Co Morbidity ◽  
Total Body ◽  
Total Body Weight Loss

Abstract Over 2.5 billion people worldwide are overweight or obese. Multidisciplinary weight management interventions have evolved to address the complexity of weight loss for those with one or more chronic diseases, and the trend of weight regain. The aim of these interventions is to encourage sustainable lifestyle changes, resulting in weight loss and weight maintenance and improvements in comorbidities. While some prospective clinical trials have demonstrated efficacy, results are often not reported by real life practices. The aim of this study was to evaluate the effectiveness of a Sydney based multidisciplinary weight management clinic with endocrinology, dietetics, exercise physiology, psychology, and bariatric surgical domains. All patients who attended the clinic for weight loss purposes between March 2017 and April 2019 were included (n=220). A retrospective chart review was conducted. Patient data on weight, BMI, waist circumference, body composition measurements, and selected blood test results and co-morbidities were analysed. All patient therapy included endocrinological input for co-morbidity identification and management, lifestyle intervention (dietetic and exercise physiology input) with optional adjunct pharmacotherapy or psychological counselling. Of the 220 cohort, 20 of the patients had sleeve gastrectomy. Patient retention in the clinic after the first consultation was 85% (n=186), a high rate within the weight management community. 59% of patients achieved a minimum of 5% total body weight loss, including 18% who achieved greater than 10% total body weight loss. Additionally, 31% of patients lost enough weight to decrease their BMI class by up to 2 or more classes. Of the gastric sleeve cohort average excess body weight loss was 32kg (21-56kg) enhanced by multidisciplinary care in the lead up to surgery. Across the cohort some patients completely reversed co-morbidities; including dyslipidaemia (n=1), hypertension (n=3), NAFLD (n=1), pre-diabetes (n=8) and type 2 diabetes (n=3), OSA (n=1). These results demonstrate that obesity is a chronic condition that can be successfully managed. We have demonstrated significant durable weight loss and improvement in metabolic co-morbidities with holistic coordinated care. Future directions include translating this model of care into standard practice in Australia and other countries where obesity to date not received the same coordinated approach as other chronic conditions.

Water Relationships of Aphis Fabae Scop. During Tethered Flight

1961 ◽  
Vol 38 (1) ◽  
pp. 175-180
Author(s):  
A. J. COCKBAIN
Keyword(s):  
Body Weight ◽  
Relative Humidity ◽  
Water Loss ◽  
Total Body Weight ◽  
Aphis Fabae ◽  
Limiting Factor ◽  
Saturation Deficit ◽  
Tethered Flight ◽  
C 23 ◽  
Total Body

1. Water content varies from 64 to 73% of the total body weight and 72-76% of the fatless body weight of 24 hr. old unflown alatae of Aphis fabae. 2. Water loss during flight may be attributed to evaporation and excretion. A mean of 0.07 mg. water is lost per aphid during a 6 hr. tethered fligh a 25-26° C. and 57-82% R.H., corresponding to c. 9% body weight; at least 66% of the loss (c. 1% body weight/hr.) is by evaporation. 3. Excretion during fligh is not affected by relative humidity differences over the range 41-75% at 25%26° C., but the relative amounts of water lost during prolonged flight are inversely related to relative humidity, because of the effect of humidity on evaporation. 4. Proportion of water in he body does no change significantly during tethered fligh. Mean percentage water to total body weight increases from c. 68-69% during 6 hr.; mean percentage water to fatless body weight decreases from c. 74 to 73%. 5. Water loss is evidently not a limiting factor to fligh in atmospheres of saturation deficit less than c. 23 mm. Hg.

Vancomycin Removal during High-Volume Peritoneal Dialysis in Acute Kidney Injury Patients

2019 ◽  
Vol 39 (2) ◽  
pp. 183-187 ◽  
Author(s):  
Daniela Ponce ◽  
Welder Zamoner ◽  
Fernanda Moreira Freitas ◽  
André Balbi ◽  
Linda Awdishu
Keyword(s):  
Acute Kidney Injury ◽  
Body Weight ◽  
Peritoneal Dialysis ◽  
Kidney Injury ◽  
High Volume ◽  
Total Body Weight ◽  
Empirical Treatment ◽  
Total Body

Studies on vancomycin pharmacokinetics in acute kidney injury (AKI) patients on high-volume peritoneal dialysis (HVPD) are lacking. We studied the pharmacokinetics of intravenous (IV) vancomycin in AKI patients treated by HVPD who received a prescribed single IV dose of vancomycin (15 - 20 mg/kg total body weight) to determine the extent of vancomycin removal and to establish vancomycin dosing guidelines for the empirical treatment of AKI patients receiving HVPD. The application of 18 mg/kg vancomycin every 48 - 72 hours in AKI patients undergoing HVPD was required to maintain therapeutic concentrations.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

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