Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species

The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half-life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aW(b), where Y is half-life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.     

Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

Cisplatin is a platinum‐containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4–55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling.     

Therapeutic hypothermia applicable to cardiac surgery

ObjectiveTo review the beneficial and adverse effects of therapeutic hypothermia (TH) applicable to cardiac surgery with cardiopulmonary bypass (CPB) in the contexts of various temperature levels and techniques for achieving TH.Databases usedMultiple electronic literature searches were performed using PubMed and Google for articles published from June 2012 to December 2014. Relevant terms (e.g. ‘hypothermia’, ‘cardiopulmonary bypass’, ‘cardiac surgery’, ‘neuroprotection’) were used to search for original articles, letters and reviews without species limitation. Reviews were included despite potential publication bias. References from the studies identified were also searched to find other potentially relevant citations. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded.ConclusionsTherapeutic hypothermia is an essential measure of neuroprotection during cardiac surgery that may be achieved most effectively by intravascular cooling using hypothermic CPB. For most cardiac surgical procedures, mild to modest (32–36 °C) TH will be sufficient to assure neuroprotection and will avoid most of the adverse effects of hypothermia that occur at lower body core temperatures.     

Perioperative physiology and pharmacology in the obese small animal patient

ObjectiveTo review the available literature concerning the physiologic and pharmacologic alterations induced by obesity in canine and feline patients and their relevance to perioperative care.Study designLiterature review.DatabasesPubmed, CAB, Web of Science.ConclusionsObesity of cats and dogs is a chronic inflammatory condition that is increasingly prevalent. Similar to the situation in humans, small animal obesity may be associated with changes in endocrine, respiratory, and cardiovascular function. In addition, alteration of body composition in obesity can affect pharmacokinetic variables. Modifications in perioperative care may need to be made for obese dogs and cats, including attention to respiratory and cardiovascular supportive care and drug dose adjustments.     

Growth of the digestive organs in ducks with considerations on their growth in birds in general.

1. Growth of the oesophagus, proventriculus, gizzard, intestine, liver and pancreas weight was investigated in Mallards, White Pekins, Muscovies and a Muscovy x White Pekin cross. The birds varied in age between hatching and 154 d. The data were analysed by fitting both the Janoschek growth curve and the allometric formula. 2. The growth rate of all organs, except the oesophagus, peaked earlier (30 d for Muscovies and 14 d for the other breeds) than body weight and they grew faster to any given percentage of their final weight. In contrast, oesophagus weight showed growth curve characteristics similar to body weight. 3. Oesophagus weight showed simple, slightly negative allometry. The remaining organs followed complex allometry that can approximately be described by 2 allometric stages. The 1st phase was isometric to positive allometric. The 2nd showed marked negative allometry. 4. These growth patterns are assumed to be generally present in birds.     

灰绿藜形态性状与繁殖性状的异速关系

通过对不同光照强度、营养和萌发时间处理条件下灰绿藜的形态指标和繁殖指标的测定,本研究探讨了灰绿藜形态性状和繁殖性状之间的异速关系及其异速生长对环境变化的响应。结果表明:灰绿藜形态性状与繁殖性状之间存在显著的异速生长关系,随着灰绿藜个体大小的增大,单个枝条的大小增速更快,并且将更多的资源分配到灰绿藜的繁殖生长。但灰绿藜的花序密度与个体大小之间具有显著的权衡关系:灰绿藜越小,花序密度越高。光照处理引起植物的繁殖性状发生了变化,但是这些变化主要是由在光照梯度下的个体大小不同造成的,繁殖策略(异速生长)未发生改变。而营养及萌发时间处理对灰绿藜的形态性状与繁殖性状间的异速关系产生了影响。营养变化对不同性状间的异速关系无一致影响,而萌发时间则具有显著的影响,晚萌发的灰绿藜将更多的资源投入到繁殖生长。     

Relationships between host species and morphometric patterns in Fasciola hepatica adults and eggs from the northern Bolivian Altiplano hyperendemic region.

The highest prevalences and intensities of human fasciolosis by Fasciola hepatica are found in the northern Bolivian Altiplano, where sheep and cattle are the main reservoir host species and pigs and donkeys the secondary ones. Morphometric comparisons of many linear measurements, areas and ratios of F. hepatica adults (from sheep, cattle and pigs) and eggs (from sheep, cattle, pigs and donkeys) in natural liver fluke populations of the Bolivian Altiplano, as well as of F. hepatica adults and eggs experimentally obtained in Wistar rats infected with Altiplanic sheep, cattle and pig isolates, were made using computer image analysis and an allometric model. Although morphometric values of adult flukes from natural populations of sheep, cattle, and pigs showed great overlap, there were clear differences in allometric growth. The allometries analyzed were: body area (BA) versus body length (BL), BA versus body width (BW), BA versus perimeter (Pe), BA versus distance between posterior end of body and ventral sucker (P-VS), BL versus BW, BL versus Pe, and BL versus P-VS. These allometries show a good fit in the seven pairs of variables in all the populations examined. Comparative statistical analysis of the allometries shows that fluke adult populations from sheep, cattle and pigs significantly differ in BL versus BW and BL versus P-VS functions. Statistical analysis of F. hepatica egg size shows characteristic morphometric traits in each definitive host species. In experimentally infected rats, fluke adult allometry and egg morphometry do not vary depending on the Altiplanic definitive host species isolate. Our study reveals that the definitive host species decisively influences the size of F. hepatica adults and eggs, and these influences do not persist in a rodent definitive host model.     

Allometric basis of enrofloxacin scaling in green iguanas

When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.     

Trait allometries generate super‐honesty in Anolis dewlaps and may underlie sexual dimorphism

Whether or not sexually selected traits consistently exhibit positive allometry (i.e. are disproportionately large in larger individuals) is an ongoing debate. Multiple models and exceptions to this rule suggest that the underlying drivers of sexual trait allometry are nuanced. Here, we compare allometries of sexual and non‐sexual traits of a species (Anolis aquaticus) within a well‐studied lizard genus to test the competing hypotheses that sexual traits are, or are not, defined by positive allometry. We further consider the relationships of trait functions, which are relatively well understood in the genus Anolis, and allometry to identify potential drivers of allometric patterns. In particular, we explore how trait allometries interact to influence total organism function and generate sexual dimorphism. We quantified size (of targeted traits) and color of a sexual signal (the dewlap) in Anolis aquaticus in the field. The dewlap conveyed information relevant to intra‐sexual combat and exhibited positive allometry. Overall, our results suggest that using single‐trait allometries as indicators of past selection provides only an incomplete understanding of trait evolution. Although the function of positive allometry in some individual sexual signals (e.g. those conveying “super‐honest” information) may be straightforward, we illustrate how scaling relationships interact synergistically to influence the function of phenotypes and propose avenues for future research.     

Allometric scaling of orbifloxacin disposition in nine mammal species: a retrospective analysis

The objective of this study was to analyze the relationship between pharmacokinetic parameters and body weight (W) for orbifloxacin using reported pharmacokinetic data. The parameters of interest: clearance (Cl), volume of distribution at steady state (Vss) and elimination half-life were correlated across nine mammal species, including cattle, dog, rat, rabbit, goat, camel, horse, cat and sheep as a function of W using the conventional allometric equation Y = aW(b), where Y is the pharmacokinetic parameter, W is the body weight, a is the allometric coefficient (intercept) and b is the exponent that describes the relationship between the pharmacokinetic parameter and W. Our estimates (Cl=4.40 W(1.03); Vss=1.10W(1.05)) indicated that the increase in these parameters with W approximates a linear power relationship with slopes being very close to one. Overall, the results of this study indicated that it is possible to use allometry to predict pharmacokinetic variables of orbifloxacin based on W of mammal species.     

A systematic review of the effects of injectable sedative and anesthetic drugs and inhalant anesthetics on intraocular pressure in the dog

ObjectiveThe purpose of this systematic review was to summarize the results of studies that have determined the effect of injectable and inhalant drugs used in anesthesia on intraocular pressure (IOP) in dogs.Databases usedA comprehensive search of research literature was performed without language restriction. The search utilized the PubMed, CAB Abstracts and the University of Georgia’s Galileo electronic databases using a combination of free text terms ‘Ophthalmology’, ‘Intraocular Pressure’, ‘Anesthetic’, ‘Anesthesia’, ‘Canine’ or ‘Dog’. The time frame searched was from 1970 to October 2018. Any published research paper that dealt with sedatives or anesthetics administered systemically and the canine eye was evaluated.ConclusionsThe effects of many anesthetic drugs in dogs with ocular pathology are largely unknown. Many anesthetic drugs do not induce clinically relevant changes in IOP in dogs with normal eyes, although some studies demonstrated results with statistically significant changes. The dose, route of administration, experimental conditions, drug combinations, timing of measurements, measurement technology and setting or individual animal characteristics may all produce some heterogeneity in results from multiple studies.     

短命植物小车前构件属性特征及其相互关系

以准噶尔荒漠广泛分布的短命植物小车前(Plantago minuta)为研究对象,通过野外调查取样,系统分析了植物构件形态、生物量分配特征及其异速比例关系。结果表明,小车前体型较小,全株生物量仅有0.402 3g;根冠比为0.157,繁殖分配和叶片生物量分别占44.2%和36.9%,生物量分配具有个体大小依赖。小车前形态指标之间、构件生物量之间及二者之间多具有显著相关性(P0.05)和异速比例关系,其中构件生物量间多为等比例关系(异速指数=1),形态指标间多为指数1的异速比例关系,而形态特征与生物量间多为指数1的异速比例关系,本研究部分验证了理论预测。构件水平差异化的异速比例关系体现了小车前不同构件对外界环境和内在发育规律的不同响应和适应特征。     

Sexual Dimorphism of Endocranial,Facial and Limb Measurements in the Yellow Baboon (Papio cynocephalus)

The present study focused on the sexual dimorphism of yellow baboon (Papio cynocephalus) to clarify its relationship with social behaviour. The degree of sexual dimorphism in the endocranial volume is the lowest among the investigated measurements. Among the facial measurements, the degree value of sexual dimorphism was the maximum (38.4%) for palate length and the minimum for palate breadth at the upper second molar (M2) (16.8%). Reduced major axis (RMA) regression analysis indicated that most positive allometry in relation to body mass was barely shown in the endocranial volume, palate length, palate breadth at M2 and mandibular ramal width. On the other hand, most negative allometry in relation to body mass was barely indicated in the bizygomatic breadth, skull length, humeral length and femoral length. The plate breadth at M2 in males was smaller than that in females in equivalent to body mass. The results of the present study suggest that more males have longer pointed muzzles than females, which is considered to create an impressive view of large canine teeth. This contributes to display among males and agonistic encounters rather than to necessity of increased facial size due to larger body size or dietary influences.     

种群密度对沙米异速生长的影响

植物各器官之间的异速生长关系决定了植物的生活史对策,进而影响种群内个体之间的共存和生物多样性的维持。传统方法无法区分植物性状对其的响应是环境造成的,还是由于个体大小差异造成的,而异速生长分析能够解决这一问题。为此,本研究利用异速生长分析方法,通过模拟沙米在退化草地恢复过程中不同的种群密度(16, 44.4, 100和400株/m²),研究其各器官之间的异速生长关系。结果表明,沙米各器官之间都具有显著的异速生长关系:其中根和地上、根和主茎、叶和根、主茎和地上等器官生物量之间的变化不随种群密度的变化而变化,属于表观可塑性;根和茎、茎和地上、叶和茎等器官生物量之间的异速生长及生物量比值均受种群密度的显著影响,属于真正可塑性,这表明种群密度变化的确影响了沙米的生长变化。研究同时发现,沙米叶和地上生物量之间的异速指数仅在44.4株/m²种群密度下接近于0.75,即叶生物量与个体大小呈3/4次幂关系,符合生态代谢理论,而在其他密度时异速指数与0.75有显著差异(P<0.001),表明环境变化可能会导致沙米生长策略发生改变。种群密度对沙米繁殖和其他器官之间的异速生长关系影响不显著,表明在不同种群密度下,沙米仍保持相同的繁殖策略;然而种群密度在沙米生育期对繁殖和其他器官之间的异速常数和个体大小均产生了极显著的影响。因此,在探讨繁殖器官与个体大小的关系时,还需要关注植物生育期的变化,只有生育期相同的时候,才能比较不同研究之间的差异。     

Genetic evaluation for latent variables derived from factor analysis in broilers

ABSTRACT

1. The aim of this study was to investigate the associations between several carcass, performance and meat quality traits in broilers through factor analysis and use the latent variables (i.e. factors) as pseudo-phenotypes in genetic evaluations.

2. Factors were extracted using the principal components method and varimax rotation algorithm. Genetic parameters were estimated via Bayesian inference under a multiple-trait animal model.

3. All factors taken together explained 71% of the original variance of the data. The first factor, denominated as ‘weight’, was associated with carcass and body weight traits; and the second factor, defined as ‘tenderness’, represented traits related to water-holding capacity and shear force. The third factor, ‘colour’, was associated with traits related to meat colour, whereas the fourth, referenced as ‘viscera’, was related to heart, liver and abdominal fat.

4. The four biological factors presented moderate to high heritability (ranging from 0.35 to 0.75), which may confer genetic gains in this population.

5. In conclusion, it seems possible to reduce the number of traits in the genetic evaluation of broilers using latent variables derived from factor analysis.     

Effects of intravenous ethyl pyruvate on cardiopulmonary variables and quality of recovery from anesthesia in horses

ObjectiveTo determine the effects of intravenous ethyl pyruvate, an anti-inflammatory with putative benefits in horses with endotoxemia, on cardiopulmonary variables during anesthesia and the quality of anesthetic recovery.Study designRandomized, crossover, blinded experimental design.AnimalsA total of six healthy Standardbred geldings, aged 13 ± 3 years and weighing 507 ± 66 kg (mean ± standard deviation).MethodsHorses were anesthetized for approximately 90 minutes on two occasions with a minimum of 2 weeks apart using xylazine for sedation, ketamine and diazepam for induction, and isoflurane in oxygen for maintenance. Lactated Ringer’s solution (LRS; 10 mL kg^–1 hour^–1) was administered during anesthesia. Treatments were randomized and administered starting approximately 30 minutes after induction of anesthesia and infused over 60 minutes: LRS (1 L) or ethyl pyruvate (150 mg kg^–1 in 1 L LRS). Invasive arterial pressures, heart rate, respiratory rate and end-tidal carbon dioxide tensions were recorded every 5 minutes for the duration of anesthesia. Arterial blood gases, glucose and lactate concentrations were measured every 20 minutes. Anesthetic recovery was video recorded, stored, and subsequently rated by two individuals blinded to treatments. Total recovery time, time to extubation, number of attempts and time to sternal recumbency, number of attempts to stand and time to stand were recorded. Quality of recovery was analyzed. Data between treatments and within a treatment were assessed using two-way repeated-measures anova and a Pearson correlation coefficient, significant at p < 0.05.ResultsAll horses completed the study. No significant differences were detected between the ethyl pyruvate and LRS treatments for either the cardiopulmonary variables or quality of recovery from anesthesia.Conclusions and clinical relevanceThe results suggest that intravenous ethyl pyruvate can be administered to healthy anesthetized horses with minimal impact on the cardiopulmonary variables studied or the quality of recovery from anesthesia.     

Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses‐ a controlled clinical trial

ObjectivesTo determine the influence of ketamine or xylazine constant rate infusions on isoflurane requirements, cardiovascular parameters and quality of anaesthesia in horses undergoing elective surgery.Study designProspective, matched paired clinical trial.AnimalsFifty four adult Warmblood horses.MethodsAfter premedication with acepromazine, xylazine and butorphanol, anaesthesia was induced with ketamine-midazolam and maintained with isoflurane alone (I), isoflurane with either 1 mg kg⁻¹ hour⁻¹ ketamine (IK) or same dose of xylazine (IX). End tidal concentration of isoflurane (Fe’Iso) was adjusted by the same anaesthetist in all horses according to a scoring system. Dobutamine was infused to maintain mean arterial pressure (MAP) =70 mmHg. Arterial blood gases, heart rate (HR), respiratory rate, MAP and cardiac output (lithium dilution) were measured. Groups I and IK received xylazine before recovery. Recovery quality was scored.ResultsMean ± SD averaged Fe’Iso (volume%) was significantly lower in IX (0.95 ± 0.07) and IK (0.97 ± 0.08) than in I (1.16 ± 0.13). In group IX, HR was significantly lower and averaged MAP (90 ± 13 mmHg) significantly higher than in groups I (71 ± 7 mmHg) and IK (76 ± 7 mm Hg). Differences in other cardiopulmonary variables did not reach statistical significance. All horses recovered well with best score in group IX.ConclusionsBoth CRIs of xylazine and of ketamine resulted in pronounced reduction of isoflurane requirements and blood pressure support based on routinely monitored parameters. Cardiac output appeared well maintained in all three protocols, but lithium dilution induced errors mean the results are untrustworthy. The work requires repetition with another mode of measurement of cardiac output.Clinical relevanceAll three protocols provided good clinical anaesthesia with clinically acceptable cardiovascular effects.     

Interspecies allometric scaling: prediction of clearance in large animal species: part II: mathematical considerations

Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. However, it is important to appreciate the mathematical underpinnings of this scaling procedure when using it to predict pharmacokinetic parameter values across animal species. When cautiously applied, allometry can be a tool for estimating clearance in veterinary species for the purpose of dosage selection. It is particularly valuable during the selection of dosages in large zoo animal species, such as elephants, large cats and camels, for which pharmacokinetic data are scant. In Part I, allometric predictions of clearance in large animal species were found to pose substantially greater risks of inaccuracies when compared with that observed for humans. In this report, we examine the factors influencing the accuracy of our clearance estimates from the perspective of the relationship between prediction error and such variables as the distribution of body weight values used in the regression analysis, the influence of a particular observation on the clearance estimate, and the 'goodness of fit' (R(2)) of the regression line. Ultimately, these considerations are used to generate recommendations regarding the data to be included in the allometric prediction of clearance in large animal species.     

Muscle growth in wild and domestic ducks

1. Increases in weight of the M. pectoralis, M. iliotibialis lateralis and M. flexor cruris lateralis were measured in mallards, White Pekins, Muscovies and a Muscovy × White Pekin cross from hatching to 154 days of age. Growth with respect to age was analysed using the Janoschek growth curve. 2. The M. pectoralis was less developed at hatching than both leg muscles. Furthermore, it showed a slower growth to its final weight and a later age at maximum growth than both leg muscles. 3. Pekins exhibited a faster Pectoralis and Iliotibialis lateralis muscle growth than mallards and Muscovies. The latter attained greater weights than Pekins at later ages owing to a higher asymptote. The cross showed the fastest muscle growth. 4. With respect to body weight, the Pectoralis is characterised by isometry followed by strongly positive allometry. This multiphasic allometry implies that relative muscle weights should not be used and the value of the allometric exponent strongly depends on both the beginning and duration of the period of investigation. Leg muscles showed isometric to slightly negative, simple allometry.     

A systematic review of sevoflurane and isoflurane minimum alveolar concentration in domestic cats

ObjectiveThe purpose of this systematic review is to summarize the results of studies which have determined the minimum alveolar concentration (MAC) of isoflurane and sevoflurane in domestic cats.Study DesignSystematic review.AnimalsCats.Methods usedA comprehensive search of research literature was performed without language restriction. The search utilized the Pubmed, Google Scholar, and CAB Abstracts electronic databases using a combination of free text terms ‘Minimum alveolar concentration’, ‘sevoflurane’, ‘isoflurane’, ‘anesthetic’, ‘cat’, ‘cats’ or ‘feline’. The search was conducted from November 2010 to June 2012.ResultsThe MAC for isoflurane ranged from 1.20 ± 0.13% to 2.22 ± 0.35% and the MAC for sevoflurane ranged from 2.5 ± 0.2% to 3.95 ± 0.33%. The average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%.Conclusions &; Clinical RelevanceThe average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%. Methodology differed among studies, and particular attention should be paid in the future to appropriate reporting of methods to allow sound conclusions to be made from the results.