Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys.
Ontology highlight
ABSTRACT:
SUBMITTER: Pozniak B
PROVIDER: S-EPMC8467158 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Rapid weight gain in turkeys causes a major change in the pharmacokinetics of drugs, leading to age-dependent variability in the internal exposure and, possibly, treatment failure and/or selection for antimicrobial resistance in young individuals. The aim of the study was to investigate whether a non-linear dosing protocol that accounts for the previously established allometric relation between enrofloxacin clearance and body weight (BW) may optimize the internal exposure to enrofloxacin in growing male turkeys. Enrofloxacin was administered four times, between the age of 5 and 16.5 weeks, when the turkeys' BW increased from 1.47 to 14.92 kg. Enrofloxacin was given intravenously (i.v.) or orally at the dose calculated as follows: Dose = 30 × BW0.59. After i.v. administration, the internal exposure to the drug-quantified as the area under the concentration-time curve (AUC)-was showing little age-related variation. The coefficient of variation (CV) for AUC in all individuals (15.7%) was only slightly higher than within the age groups (5.4-13.7%). After oral drug administration, CV for AUC in all individuals (22.1%) was similar as within the age groups (8.7-32.2%). These results show that intra-species allometric scaling may be efficiently implemented in the non-linear approach to enrofloxacin dosage in turkeys in order to obtain a precise internal exposure for the optimal antimicrobial effect.
| S-EPMC7766516 | biostudies-literature
Project description:About two decades ago, West and coworkers established a model which predicts that metabolic rate follows a three quarter power relationship with the mass of an organism, based on the premise that tissues are supplied nutrients through a fractal distribution network. Quarter power scaling is widely considered a universal law of biology and it is generally accepted that were in-vitro cultures to obey allometric metabolic scaling, they would have more predictive potential and could, for instance, provide a viable substitute for animals in research. This paper outlines a theoretical and computational framework for establishing quarter power scaling in three-dimensional spherical constructs in-vitro, starting where fractal distribution ends. Allometric scaling in non-vascular spherical tissue constructs was assessed using models of Michaelis Menten oxygen consumption and diffusion. The models demonstrate that physiological scaling is maintained when about 5 to 60% of the construct is exposed to oxygen concentrations less than the Michaelis Menten constant, with a significant concentration gradient in the sphere. The results have important implications for the design of downscaled in-vitro systems with physiological relevance.
| S-EPMC5294453 | biostudies-other
Project description:Metabolic rate, heart rate, lifespan, and many other physiological properties vary with body mass in systematic and interrelated ways. Present empirical data suggest that these scaling relationships take the form of power laws with exponents that are simple multiples of one quarter. A compelling explanation of this observation was put forward a decade ago by West, Brown, and Enquist (WBE). Their framework elucidates the link between metabolic rate and body mass by focusing on the dynamics and structure of resource distribution networks-the cardiovascular system in the case of mammals. Within this framework the WBE model is based on eight assumptions from which it derives the well-known observed scaling exponent of 3/4. In this paper we clarify that this result only holds in the limit of infinite network size (body mass) and that the actual exponent predicted by the model depends on the sizes of the organisms being studied. Failure to clarify and to explore the nature of this approximation has led to debates about the WBE model that were at cross purposes. We compute analytical expressions for the finite-size corrections to the 3/4 exponent, resulting in a spectrum of scaling exponents as a function of absolute network size. When accounting for these corrections over a size range spanning the eight orders of magnitude observed in mammals, the WBE model predicts a scaling exponent of 0.81, seemingly at odds with data. We then proceed to study the sensitivity of the scaling exponent with respect to variations in several assumptions that underlie the WBE model, always in the context of finite-size corrections. Here too, the trends we derive from the model seem at odds with trends detectable in empirical data. Our work illustrates the utility of the WBE framework in reasoning about allometric scaling, while at the same time suggesting that the current canonical model may need amendments to bring its predictions fully in line with available datasets.
| S-EPMC2518954 | biostudies-literature
Project description:There are still significant uncertainties in the magnitude and direction of carbon fluxes through coastal ecosystems. An important component of these biogeochemical budgets is ecosystem metabolism, the net result of organismal metabolic processes within an ecosystem. In this paper, I present a synthesis of published ecosystem metabolism studies from coastal ecosystems and describe an empirical observation that size-dependent patterns in aquatic gross primary production and community respiration exist across a wide range of coastal geomorphologies. Ecosystem metabolism scales to the 3/4 power with volume in deeper estuaries dominated by pelagic primary production and nearly linearly with area in shallow estuaries dominated by benthic primary production. These results can be explained by applying scaling arguments for efficient, directed transport networks developed to explain similar size-dependent patterns in organismal metabolism. The main conclusion from this synthesis is that the residence time of new, nutrient-rich water is a fundamental organizing principle for the observed patterns. Residence time changes allometrically with size in pelagic ecosystems because velocities change by only an order of magnitude across systems that span more than ten orders of magnitude in size. This nonisometric change in velocity with size requires lower specific metabolic rates at larger ecosystem sizes. This change in transport may also explain a shift from predominantly net heterotrophy to net autotrophy with increasing size. The scaling results are applied to the total estuarine area in the continental United States to estimate the contribution of estuarine systems to the overall coastal budget of organic carbon.
| S-EPMC6042108 | biostudies-literature
Project description:Allometric scaling relationships enable exploration of animal space-use patterns, yet interspecific studies cannot address many of the underlying mechanisms. We present the first intraspecific study of home range (HR) allometry relative to energetic requirements over several orders of magnitude of body mass, using as a model the predatory fish, pike Esox lucius. Analogous with interspecific studies, we show that space use increases more rapidly with mass (exponent = 1.08) than metabolic scaling theories predict. Our results support a theory that suggests increasing HR overlap with body mass explains many of these differences in allometric scaling of HR size. We conclude that, on a population scale, HR size and energetic requirement scale allometrically, but with different exponents.
| S-EPMC4843214 | biostudies-literature
Project description:Plant mortality and birth rates are critical components of plant life history affecting the stability of plant populations and the ecosystems they form. Although allometric theory predicts that both plant birth and mortality rates should be size-dependent, this prediction has not yet been tested across plants ranging the full size spectrum. Here we show that both population mortality and population birth rates scale as the -(1/4) power and plant lifespan as the (1/4) power of plant mass across plant species spanning from the tiniest phototrophs to the largest trees. Whereas the controls on plant lifespans are as yet poorly understood, our findings suggest that plant mortality rates have evolved to match population birth rates, thereby helping to maintain plant communities in equilibrium and optimizing plant life histories.
| S-EPMC1989662 | biostudies-literature
Project description:The functional and structural resemblance of organoids to mammalian organs suggests that they might follow the same allometric scaling rules. However, despite their remarkable likeness to downscaled organs, non-luminal organoids are often reported to possess necrotic cores due to oxygen diffusion limits. To assess their potential as physiologically relevant in vitro models, we determined the range of organoid masses in which quarter power scaling as well as a minimum threshold oxygen concentration is maintained. Using data on brain organoids as a reference, computational models were developed to estimate oxygen consumption and diffusion at different stages of growth. The results show that mature brain (or other non-luminal) organoids generated using current protocols must lie within a narrow range of masses to maintain both quarter power scaling and viable cores. However, micro-fluidic oxygen delivery methods could be designed to widen this range, ensuring a minimum viable oxygen threshold throughout the constructs and mass dependent metabolic scaling. The results provide new insights into the significance of the allometric exponent in systems without a resource-supplying network and may be used to guide the design of more predictive and physiologically relevant in vitro models, providing an effective alternative to animals in research.
| S-EPMC6695443 | biostudies-literature
Project description:Deferoxamine (DFO) is an effective FDA-approved iron chelator; however, its use is considerably limited by off-target toxicities and an extremely cumbersome dose regimen involving daily infusions. The recent development of a deferoxamine-based nanochelator (DFO-NP) with selective renal excretion has shown promise in ameliorating iron overload and associated physiological complications in rodent models with a substantially improved safety profile. While the dose- and administration route-dependent pharmacokinetics (PK) of DFO-NPs have been recently characterized, the optimized PK model was not validated, and the prior studies did not directly address the clinical translatability of DFO-NPs into humans. In the present work, these gaps were addressed by applying allometric scaling of DFO-NP PK in rats to predict those in mice and humans. First, this approach predicted serum concentration-time profiles of DFO-NPs, which were similar to those experimentally measured in mice, validating the nonlinear disposition and absorption models for DFO-NPs across the species. Subsequently, we explored the utility of allometric scaling by predicting the PK profile of DFO-NPs in humans under clinically relevant dosing schemes. These in silico efforts demonstrated that the novel nanochelator is expected to improve the PK of DFO when compared to standard infusion regimens of native DFO. Moreover, reasonable formulation strategies were identified and discussed for both early clinical development and more sophisticated formulation development.
| S-EPMC10399172 | biostudies-literature
Project description:Biotransformation may substantially impact the toxicity and accumulation of xenobiotic chemicals in fish. However, this activity can vary substantially within and among species. In this study, liver S9 fractions from rainbow trout (4-400?g) were used to evaluate relationships between fish body mass and the activities of phase I and phase II metabolic enzymes. An analysis of log-transformed data, expressed per gram of liver (g?liver-1), showed that total cytochrome P450 (CYP) concentration, UDP-glucuronosyltransferase (UGT) activity, and glutathione S-transferase (GST) activity exhibited small but significant inverse relationships with fish body weight. In contrast, in vitro intrinsic clearance rates (CLIN VITRO,INT) for three polycyclic aromatic hydrocarbons (PAHs) increased with increasing body weight. Weight normalized liver mass also decreased inversely with body weight, suggesting a need to express hepatic metabolism data per gram of body weight (g?BW-1) in order to reflect the metabolic capabilities of the whole animal. When the data were recalculated in this manner, negative allometric relationships for CYP concentration, UGT activity, and GST activity became more pronounced, while CLIN VITRO,INT rates for the three PAHs showed no significant differences across fish sizes. Ethoxyresorufin O-deethylase (EROD) activity normalized to tissue weight (g?liver-1) or body weight (g?BW-1) exhibited a non-monotonic pattern with respect to body weight. The results of this study may have important implications for chemical modeling efforts with fish.
| S-EPMC6349251 | biostudies-literature
Project description:A long-standing interest in marine science is in the degree to which environmental conditions of flow and irradiance, combined with optical, thermal and morphological characteristics of individual coral colonies, affects their sensitivity of thermal microenvironments and susceptibility to stress-induced bleaching within and/or among colonies. The physiological processes in Scleractinian corals tend to scale allometrically as a result of physical and geometric constraints on body size and shape. There is a direct relationship between scaling to thermal stress, thus, the relationship between allometric scaling and rates of heating and cooling in coral microenvironments is a subject of great interest. The primary aim of this study was to develop an approximation that predicts coral thermal microenvironments as a function of colony morphology (shape and size), light or irradiance, and flow velocity or regime. To do so, we provided intuitive interpretation of their energy budgets for both massive and branching colonies, and then quantified the heat-size exponent (b*) and allometric constant (m) using logarithmic linear regression. The data demonstrated a positive relationship between thermal rates and changes in irradiance, A/V ratio, and flow, with an interaction where turbulent regime had less influence on overall stress which may serve to ameliorate the effects of temperature rise compared to the laminar regime. These findings indicated that smaller corals have disproportionately higher stress, however they can reach thermal equilibrium quicker. Moreover, excellent agreements between the predicted and simulated microscale temperature values with no significant bias were observed for both the massive and branching colonies, indicating that the numerical approximation should be within the accuracy with which they could be measured. This study may assist in estimating the coral microscale temperature under known conditions of water flow and irradiance, in particular when examining the intra- and inter-colony variability found during periods of bleaching conditions.
| S-EPMC5638381 | biostudies-literature