Possible Mechanism by Which the Carbapenem Antibiotic Panipenem Decreases the Concentration of Valproic Acid in Plasma in Rats

ABSTRACT There is evidence indicating that the carbapenem antibiotic panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy. The mechanism for panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation. The effect of panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined. VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma panipenem concentration of 4 μg/ml, which had been achieved by a constant infusion rate. Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA. However, panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation. The secondary increase in plasma diclofenac concentration observed in the absence of panipenem was diminished in the presence of panipenem. These findings suggest that panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a panipenem-induced decrease in the numbers of enteric bacteria.

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Temperature-Induced Changes in Metabolism and Body Weight of Cattle (Bos taurus)

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y75-129 ◽

1975 ◽

Vol 53 (5) ◽

pp. 947-953 ◽

Cited By ~ 24

Author(s):

B. A. Young

Keyword(s):

Body Weight ◽

Prolonged Exposure ◽

Metabolic Response ◽

Bos Taurus ◽

Plasma Concentrations ◽

Beef Cows ◽

Weight Changes ◽

Daily Food ◽

Concomitant Reduction ◽

Induced Changes

The metabolic and body weight changes in two non-pregnant beef cows were studied during prolonged exposure to warm (20 ± 3 °C, relative humidity 50–70%) and cold (−10 ± 2 or −25 ± 4 °C) temperatures. Other factors including daily food intake were held constant throughout each 8-week exposure. During cold exposures, metabolic rate, blood hematocrit, and plasma concentrations of glucose and free fatty acid were elevated and respiratory frequencies and skin temperatures decreased. Resting metabolic rates measured at 20 °C, i.e., without the direct influence of cold, were 83.4–95.3 litres O2 per hour when the cows were cold acclimated, at either −10 or −25 °C, and 30–40% greater than when the cows were warm acclimated. The resting metabolic response and the concomitant reduction in intensity of shivering is indicative of metabolic acclimation to cold in these animals of greater than 500 kg body weight.As well as the expected changes in body weight with changes in energy metabolism there were losses in weight (13–24 kg) during the first 3 days of each cold exposure. Weight gains occurred when the cold stress was abruptly removed. These short term weight changes were associated with changes in water intake and apparent shifts in body fluid content.

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INFLUENCE OF METYRAPONE ON PLASMA CONCENTRATIONS OF TESTOSTERONE AND ANDROSTENEDIONE IN MAN

Acta Endocrinologica ◽

10.1530/acta.0.0680576 ◽

1971 ◽

Vol 68 (3) ◽

pp. 576-584 ◽

Cited By ~ 5

Author(s):

K. O. Nilsson ◽

B. Hökfelt

Keyword(s):

Body Weight ◽

Male Patient ◽

Gradual Increase ◽

Plasma Concentrations ◽

Plasma Testosterone ◽

Testosterone Levels ◽

Basal Plasma ◽

Normal Males ◽

A Minor ◽

Secondary Hypogonadism

ABSTRACT Metyrapone was administered either orally, 750 mg every four h, in a total of six doses, or intravenously 30 mg per kg body weight as a four h infusion. In three males with normal endocrine functions, metyrapone given orally or intravenously induced a fall in plasma testosterone and an elevation of androstenedione within 2–8 h. When metyrapone was administered to a patient given dexamethasone to suppress endogenous ACTH production, the androstenedione levels did not alter whereas the testosterone levels showed a slight, transient decrease. In two normal females metyrapone administration was followed by a marked increase in plasma androstenedione whereas testosterone showed only a minor, gradual increase. In one male patient with Addison's disease the basal plasma testosterone was normal whereas the level of androstenedione was low. Following metyrapone intravenously, there was a slight suppression of plasma testosterone but no change in the androstenedione concentration. In one patient with primary hypogonadism, two with secondary hypogonadism and two with Klinefelter's syndrome the plasma testosterone was low under basal conditions and did not change following metyrapone. Basal plasma androstenedione was within the range for normal males and increased markedly following metyrapone in all the cases.

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Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽

10.1530/reprod/119.1.151 ◽

2000 ◽

pp. 151-156 ◽

Cited By ~ 12

Author(s):

E Diaz ◽

D Pazo ◽

AI Esquifino ◽

B Diaz

Keyword(s):

Body Weight ◽

Reproductive System ◽

Plasma Concentrations ◽

Pituitary Hormones ◽

Female Rats ◽

Control Groups ◽

Melatonin Treatment ◽

Exogenous Melatonin ◽

Reproductive Axis ◽

Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

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Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes

Cells ◽

10.3390/cells9020464 ◽

2020 ◽

Vol 9 (2) ◽

pp. 464 ◽

Cited By ~ 1

Author(s):

Bright Asare-Bediako ◽

Sunil Noothi ◽

Sergio Li Calzi ◽

Baskaran Athmanathan ◽

Cristiano Vieira ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Fundus Photography ◽

Vascular Density ◽

Sensitivity Index ◽

High Fat ◽

Permeability Studies ◽

Induced Changes ◽

Acellular Capillaries

We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes.

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Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

Scientific Reports ◽

10.1038/s41598-021-87293-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dominika Stygar ◽

Tomasz Sawczyn ◽

Agnieszka Dulska ◽

Elżbieta Chełmecka ◽

Łukasz Mielańczyk ◽

...

Keyword(s):

Body Weight ◽

Plasma Levels ◽

Plasma Concentrations ◽

The Body ◽

Retinol Binding Protein ◽

Fibroblast Growth Factor 21 ◽

Adult Males ◽

Total Lipids ◽

Ileal Transposition ◽

Sham Surgery

AbstractWe studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

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Physiologically Based Pharmacokinetic Modelling of Cabozantinib to Simulate Enterohepatic Recirculation, Drug–Drug Interaction with Rifampin and Liver Impairment

Pharmaceutics ◽

10.3390/pharmaceutics13060778 ◽

2021 ◽

Vol 13 (6) ◽

pp. 778

Author(s):

Bettina Gerner ◽

Oliver Scherf-Clavel

Keyword(s):

Hepatic Impairment ◽

Kinase Inhibitor ◽

Plasma Concentrations ◽

Area Under The Curve ◽

Enterohepatic Recirculation ◽

Maximum Plasma ◽

Good Precision ◽

Physiologically Based Pharmacokinetic ◽

Starting Point ◽

Physiologically Based

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor approved for the treatment of several cancer types. Enterohepatic recirculation (EHC) of the substance is assumed but has not been further investigated yet. CAB is mainly metabolized via CYP3A4 and is susceptible for drug–drug interactions (DDI). The goal of this work was to develop a physiologically based pharmacokinetic (PBPK) model to investigate EHC, to simulate DDI with Rifampin and to simulate subjects with hepatic impairment. The model was established using PK-Sim® and six human clinical studies. The inclusion of an EHC process into the model led to the most accurate description of the pharmacokinetic behavior of CAB. The model was able to predict plasma concentrations with low bias and good precision. Ninety-seven percent of all simulated plasma concentrations fell within 2-fold of the corresponding concentration observed. Maximum plasma concentration (Cmax) and area under the curve (AUC) were predicted correctly (predicted/observed ratio of 0.9–1.2 for AUC and 0.8–1.1 for Cmax). DDI with Rifampin led to a reduction in predicted AUC by 77%. Several physiological parameters were adapted to simulate hepatic impairment correctly. This is the first CAB model used to simulate DDI with Rifampin and hepatic impairment including EHC, which can serve as a starting point for further simulations with regard to special populations.

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Influence ofABCC2andABCC4Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04930-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3240-3245 ◽

Cited By ~ 26

Author(s):

Kanokrat Rungtivasuwan ◽

Anchalee Avihingsanon ◽

Narukjaporn Thammajaruk ◽

Siwaporn Mitruk ◽

David M. Burger ◽

...

Keyword(s):

Body Weight ◽

Multivariate Analysis ◽

Plasma Concentration ◽

Protease Inhibitors ◽

Demographic Data ◽

Plasma Concentrations ◽

Multidrug Resistant ◽

Cross Sectional Study ◽

Cross Sectional ◽

The Mean

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)

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Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.1.r113 ◽

1997 ◽

Vol 273 (1) ◽

pp. R113-R120 ◽

Cited By ~ 43

Author(s):

B. Ahren ◽

S. Mansson ◽

R. L. Gingerich ◽

P. J. Havel

Keyword(s):

Body Weight ◽

Dietary Fat ◽

High Fat Diet ◽

Plasma Insulin ◽

Plasma Concentrations ◽

Age Groups ◽

Fat Content ◽

High Fat ◽

Background Strain ◽

Plasma Leptin

Mechanisms regulating circulating leptin are incompletely understood. We developed a radioimmunoassay for mouse leptin to examine the influence of age, dietary fat content, and fasting on plasma concentrations of leptin in the background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at 11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r = 0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012) but not with the initial body weight or the change in body weight. Moreover, the reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates with body weight, fat content, and plasma insulin; and 3) is reduced during fasting by an action inhibited by high-fat diet and related to changes of plasma insulin.

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Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet

Scientific Reports ◽

10.1038/s41598-021-82837-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Valter Tadeu Boldarine ◽

Ellen Joyce ◽

Amanda Paula Pedroso ◽

Mônica Marques Telles ◽

Lila Missae Oyama ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Neutral Lipids ◽

Saturated Fat ◽

Metabolic Effects ◽

Cholesteryl Esters ◽

Ovx Rats ◽

Lipid Species ◽

Retroperitoneal White Adipose Tissue ◽

Induced Changes

AbstractMenopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17β-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-β indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-β index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono–Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono–Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono–Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.

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WING MOVEMENTS AND LIFT REGULATION IN THE FLIGHT OF DESERT LOCUSTS

Journal of Experimental Biology ◽

10.1242/jeb.182.1.57 ◽

1993 ◽

Vol 182 (1) ◽

pp. 57-69 ◽

Cited By ~ 6

Author(s):

M. Wortmann ◽

W. Zarnack

Keyword(s):

Body Weight ◽

Unsteady Aerodynamics ◽

Movement Patterns ◽

The Body ◽

Three Dimensions ◽

Body Angle ◽

Wing Movement ◽

Induced Changes ◽

Lift Body

1. We simultaneously recorded lift/body weight, flight speed, body angle and 12 variables of wing movement for locusts performing tethered long-term flight with low movement scatter. The movements of the forewings and hindwings were recorded in three dimensions by means of miniature induction coils. 2. By adjusting the body angle, we could reproducibly manipulate lift generation as a consequence of induced changes in the wings' movement patterns. We were therefore able to analyse various relationships between the movement patterns and lift. 3. The most prominent variations of kinematic variables were observed for the forewing movements. The relative lift and the steady angle of pitch were positively correlated but there was a negative correlation between relative lift and pitching amplitude. We found no correlation between relative lift and flapping amplitude. Our results seem to correspond to a new theory about unsteady aerodynamics of oscillating aerofoils. 4. We sometimes observed variations in lagging. 5. The forewing downstroke was delayed by 0–8 ms following the hindwing downstroke. Relative lift was positively correlated to this delay.

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