Farmakokinetika gatifloksacina u bivolje teladi nakon jednokratne intramuskularne primjene

The pharmacokinetics and in vivo plasma protein binding of gatifloxacin after a single intramuscular injection of 4 mg/kg were studied in buffalo calves. The minimum therapeutic concentration of drug was maintained in plasma from 1 min to 12 h. Gatifloxacin was rapidly absorbed from the extravascular site of injection, as evident from the high value of absorption rate constant (4.91 ± 0.22 /h) and attained a Cmax of 2.98 ± 0.08 μg/mL at 1h. The area under the plasma concentration-time curve and apparent volume of distribution were 10.8 ± 0.64 μg/mL/h and 3.2 ± 0.08 L/kg, respectively. Elimination half-life and total body clearance were 7.45 ± 0.55 h and 301.5 ± 34.4 mL/kg/h, respectively. Cmax/MIC ratio was 14.9 ± 0.3 and systemic bioavailability was 79.7 ± 3.35 per cent. Gatifloxacin was bound to plasma proteins of buffalo calves to the extent of 25.0 ± 1.05 per cent. A suitable intramuscular dosage regimen of gatifloxacin in buffalo calves would be 6.0 mg/kg followed by 5.3 mg/kg at 24 h intervals.Farmakokinetika i in vivo vezanje gatifloksacina na proteine plazme istraživani su u bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 4 mg/kg. Minimalna terapijska koncentracija lijeka održavana je u plazmi u tijeku od 1 minute do 12 sati. Gatifloksacin se brzo resorbirao s mjesta ubrizgavanja što je vidljivo po visokoj vrijednosti konstante brzine apsorpcije (4,91 ± 0,22 sati) i postignute Cmax 2,98 ± 0,08 μg/mL/sat. Površina ispod koncentracijske krivulje u plazmi iznosila je 10,8 ± 0,64 μg/mL/sat, a prividni volumen raspodjele 3,2 ± 0,08 L/kg. Poluvrijeme izlučivanja iznosilo je 7,45 ± 0,55 sati, a ukupni tjelesni klirens 301,5 ± 34,4 mL/kg/sat. Omjer Cmax/MIC bio je 14,9 ± 0,3, a sustavna bioraspoloživost iznosila je 79,7 ± 3,35%. Gatifloksacin je bio vezan na bjelančevine plazme do 25,0 ± 1,05%. Prikladno intramuskularno doziranje u bivolje teladi bilo bi 6,0 mg/kg, a u sljedećim dozama treba davati 5,3 mg/kg u razmacima od 24 sata

Farmakokinetika i doziranje levofloksacina u bivolje teladi nakon jednokratne potkožne primjene

The present study was conducted on six male buffalo calves to investigate the pharmacokinetics of levofloxacin following a single subcutaneous administration at the dose rate of 3 mg/kg body weight. Appreciable plasma concentration of levofloxacin (0.28 ± 0.01 μg/mL) was detected 2.5 min after injection and the peak plasma level of 2.94 ± 0.07 μg/mL was observed at 1 h. Drug levels of 0.28 ± 0.01 μg/mL in plasma were detected up to 12 h from administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.53 ± 0.53 /h). The absolute bioavailability of levofloxacin after subcutaneous administration calculated on the basis of AUC (10.5 ± 0.11 μg/mL/h) and Ke (0.272 ± 0.009 /h) after a single intravenous injection in buffalo calves was 44.3 ± 1.76 per cent. The high value of AUC (8.02 ± 0.2 μg/mL/h) reflected major exposure in the buffalo calves. Extensive distribution of the drug into various body fluids and tissues was reflected by the high value of Vdarea (1.06 ± 0.04 L.kg-1). The elimination half-life and MRT were 4.43 ± 0.1 h and 6.71 ± 0.17 h, respectively. On the basis of the pharmacokinetic parameters, the calculated subcutaneous dosage regimen for levofloxacin in buffalo calves was 4.6 mg/kg at 24 h intervals.Farmakokinetika levofloksacina nakon njegove jednokratne supkutane primjene u dozi od 3 mg/kg tjelesne mase određivana je na šest muške bivolje teladi. Mjerljiva koncentracija levofloksacina u plazmi (0,28 ± 0,01 μg/mL) bila je ustanovljena 2,5 minute nakon primjene, a vršna razina od 2,94 ± 0,07 μg/mL ustanovljena je jedan sat nakon primjene. Razina lijeka od 0,28 ± 0,01 μg/mL bila je u plazmi dokazana do 12 sati nakon primjene. Brza apsorpcija lijeka očitovala se u visokoj vrijednosti stupnja apsorpcije (2,53 ± 0,53/h). Apsolutna biološka raspoloživost levofloksacina nakon supkutane primjene izračunana na osnovi AUC (10,5 ± 0,11 μg/mL/h) i Ke (0,272 ± 0,009 /h) nakon jednokratne intravenske primjene iznosila je 44,3 ± 1,76%. Visoka vrijednost AUC (8,02 ± 0,2 μg/mL/h) bila je posljedica velike količine primijenjenoga lijeka. Široka raspodjela lijeka u različitim tjelesnim tekućinama i tkivima očitovala se velikom vrijednošću Vdarea (1,06 ± 0,04 L/kg). Poluživot izlučivanja lijeka iznosio je 4,43 ± 0,1 h, a MRT 6,71 ± 0,17 h. Na osnovi farmakokinetičkih pokazatelja, izračunana supkutana doza levofloksacina u bivolje teladi iznosila je 4,6 mg/kg u razmacima od 24 sata

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats.

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours

Farmakokinetika gatifloksacina u bivolje teladi nakon jednokratne intramuskularne primjene

The pharmacokinetics and in vivo plasma protein binding of gatifloxacin after a single intramuscular injection of 4 mg/kg were studied in buffalo calves. The minimum therapeutic concentration of drug was maintained in plasma from 1 min to 12 h. Gatifloxacin was rapidly absorbed from the extravascular site of injection, as evident from the high value of absorption rate constant (4.91 ± 0.22 /h) and attained a Cmax of 2.98 ± 0.08 μg/mL at 1h. The area under the plasma concentration-time curve and apparent volume of distribution were 10.8 ± 0.64 μg/mL/h and 3.2 ± 0.08 L/kg, respectively. Elimination half-life and total body clearance were 7.45 ± 0.55 h and 301.5 ± 34.4 mL/kg/h, respectively. Cmax/MIC ratio was 14.9 ± 0.3 and systemic bioavailability was 79.7 ± 3.35 per cent. Gatifloxacin was bound to plasma proteins of buffalo calves to the extent of 25.0 ± 1.05 per cent. A suitable intramuscular dosage regimen of gatifloxacin in buffalo calves would be 6.0 mg/kg followed by 5.3 mg/kg at 24 h intervals.Farmakokinetika i in vivo vezanje gatifloksacina na proteine plazme istraživani su u bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 4 mg/kg. Minimalna terapijska koncentracija lijeka održavana je u plazmi u tijeku od 1 minute do 12 sati. Gatifloksacin se brzo resorbirao s mjesta ubrizgavanja što je vidljivo po visokoj vrijednosti konstante brzine apsorpcije (4,91 ± 0,22 sati) i postignute Cmax 2,98 ± 0,08 μg/mL/sat. Površina ispod koncentracijske krivulje u plazmi iznosila je 10,8 ± 0,64 μg/mL/sat, a prividni volumen raspodjele 3,2 ± 0,08 L/kg. Poluvrijeme izlučivanja iznosilo je 7,45 ± 0,55 sati, a ukupni tjelesni klirens 301,5 ± 34,4 mL/kg/sat. Omjer Cmax/MIC bio je 14,9 ± 0,3, a sustavna bioraspoloživost iznosila je 79,7 ± 3,35%. Gatifloksacin je bio vezan na bjelančevine plazme do 25,0 ± 1,05%. Prikladno intramuskularno doziranje u bivolje teladi bilo bi 6,0 mg/kg, a u sljedećim dozama treba davati 5,3 mg/kg u razmacima od 24 sata

Impacts of Diet and Exercise on Maternal Gut Microbiota Are Transferred to Offspring

Background: It is well established that maternal exercise during pregnancy improves metabolic outcomes associated with obesity in mothers and offspring, however, its effects on the gut microbiota of both mother and offspring, are unknown. Here, we investigated whether wheel running exercise prior to and during pregnancy and prolonged feeding of an obesogenic diet were associated with changes in the gut microbiomes of Sprague-Dawley rat dams and their offspring. Female rats were fed either chow or obesogenic diet, and half of each diet group were given access to a running wheel 10 days before mating until delivery, while others remained sedentary. 16S rRNA gene amplicon sequencing was used to assess gut microbial communities in dams and their male and female offspring around the time of weaning.Results: Statistical analyses at the operational taxonomic unit (OTU) level revealed that maternal obesogenic diet decreased gut microbial alpha diversity and altered abundances of bacterial taxa previously associated with obesity such as Bacteroides and Blautia in dams, and their offspring of both sexes. Distance based linear modeling revealed that the relative abundances of Bacteroides OTUs were associated with adiposity measures in both dams and offspring. We identified no marked effects of maternal exercise on the gut microbiota of obesogenic diet dams or their offspring. In contrast, maternal exercise decreased gut microbial alpha diversity and altered the abundance of 88 microbial taxa in offspring of control dams. Thirty of these taxa were altered in a similar direction in offspring of sedentary obesogenic vs. control diet dams. In particular, the relative abundances of Oscillibacter OTUs were decreased in offspring of both exercised control dams and sedentary obesogenic diet dams, and associated with blood glucose concentrations and adiposity measures. Analyses of predicted bacterial metabolic pathways inferred decreased indole alkaloid biosynthesis in offspring of both obesogenic diet and exercised control dams.Conclusions: Our data suggest that maternal exercise prior to and during pregnancy resulted in gut dysbiosis in offspring of control dams. Importantly, alterations in the maternal gut microbiota by obesogenic diet or obesity were transferred to their offspring

EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), 2013. Scientific Opinion on the public health hazards to be covered by inspection of meat (bovine animals).

A risk ranking process identified Salmonella spp. and pathogenic verocytotoxin-producing Escherichia coli (VTEC) as current high-priority biological hazards for meat inspection of bovine animals. As these hazards are not detected by traditional meat inspection, a meat safety assurance system for the farm-to-chilled carcass continuum using a risk-based approach was proposed. Key elements of the system are risk-categorisation of slaughter animals for high-priority biological hazards based on improved food chain information, as well as risk-categorisation of slaughterhouses according to their capability to control those hazards. Omission of palpation and incision during post-mortem inspection for animals subjected to routine slaughter may decrease spreading and cross-contamination with the high-priority biological hazards. For chemical hazards, dioxins and dioxin-like polychlorinated biphenyls were ranked as being of high potential concern; all other substances were ranked as of medium or lower concern. Monitoring programmes for chemical hazards should be more flexible and based on the risk of occurrence, taking into account the completeness and quality of the food chain information supplied and the ranking of chemical substances, which should be regularly updated to include new hazards. Control programmes across the food chain, national residue control programmes, feed control and monitoring of environmental contaminants should be better integrated. Meat inspection is a valuable tool for surveillance and monitoring of animal health and welfare conditions. Omission of palpation and incision would reduce detection effectiveness for bovine tuberculosis and would have a negative impact on the overall surveillance system especially in officially tuberculosis free countries. The detection effectiveness for bovine cysticercosis, already low with the current meat inspection system, would result in a further decrease, if palpation and incision are removed. Extended use of food chain information could compensate for some, but not all, the information on animal health and welfare lost if only visual post-mortem inspection is applied

Vehicle Trajectory Prediction Using Road Structure

An autonomous vehicle should be able to operate amidst numerous other human-driven vehicles, each driving on its own trajectory. To safely navigate in such a dynamic environment, the autonomous vehicle should be able to predict trajectories of the vehicles operating in its vicinity and use these to plan its own path. Most related work uses a vehicle's past trajectory to model its behavior, based on which the future trajectory is predicted. However, they do not focus on the influence of contextual features such as road structure from the scene that may affect the vehicle's future trajectory. This work proposes an approach to predict a long-term vehicle trajectory using not only the past trajectory of a vehicle but also contextual features from the driving scene. We model the road structure to help prediction on curved road sections. A Recurrent Neural Network is used to learn vehicle behavior from past vehicle trajectories and predict future trajectories while incorporating road structure. Using a trajectory dataset collected from a test vehicle, we compare our model's performance with the conventional prediction approach based on only past vehicle trajectory

Effects of maternal diet and exercise during pregnancy on glucose metabolism in skeletal muscle and fat of weanling rats

Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring

Effects of maternal obesity and voluntary exercise prior to and during pregnancy on rat offspring

Evidence from animal models and clinical data suggest that maternal obesity programs a range of detrimental effects in offspring. Limiting gestational weight gain may be a useful strategy to reduce these effects. This thesis investigated the impact of voluntary exercise during pregnancy on health outcomes in offspring of obese and lean mothers. Female Sprague-Dawley rats were fed chow (C n=28) or high fat (F n=32) diet for 6 weeks. Ten days before mating, half of each group were offered voluntary exercise with a running wheel (CE/FE); the others remained sedentary (CS/FS). Wheel access continued until parturition. Pup body weight (BW) was monitored and two pups from each mother were killed at postnatal day (PND)19. Thereafter siblings were fed chow. At 5-6 weeks, male pups were tested for anxiety on the Elevated Plus Maze (EPM); all offspring were killed at 13 weeks (adult) for metabolic assessment.Lean and obese mothers showed similar modest levels of exercise with no significant effect on maternal BW. At PND1, lean exercised mothers had lighter male and female pups with no effect in those from obese mothers. At PND19, maternal obesity increased offspring BW and adiposity with no effect of exercise. Exercise reduced insulin concentrations in males, with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle MYOD1 and GLUT4 mRNA expression and these were normalised by exercise. Maternal exercise upregulated adipose GLUT4, IL6, TNFα, and PGC1α mRNA expression in CE offspring. Maternal obesity had no effect on anxiety-like behavior while CE offspring showed increased anxiety-like behavior. Adult FS males had higher plasma insulin, leptin and triglyceride concentrations, which were normalised by maternal exercise, while in females only the insulin concentration was raised. In males, hippocampus TLR4, FTO and IL-1β mRNA expression were upregulated by maternal obesity, and normalised by exercise.Taken together, maternal obesity increased the risk of metabolic disease in offspring, with higher BW, adiposity, hyperleptinemia, hyperinsulinemia and increased brain inflammatory markers. Modest levels of maternal exercise appeared to decrease the metabolic risk induced by maternal obesity. Exercise had sex-specific benefits that were more marked in male offspring