Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated‐measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed‐rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC‐MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vd_ss/F) and increased mean residence time (MRT) for NANO. One‐compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.     

Effects of road transportation or droving on the weight and metabolism of young bulls

This study evaluated the effects of the mode of transportation on weight and metabolism of young bulls, which are generally transported by two systems: droving and truck. This experiment consisted of two phases: transportation and refeeding and involved transportation by droving and truck. Fifty young Nellore bulls were separated in equal numbers in both groups, droving group and truck group. In the transportation phase, animals were moved, in a 640-km journey. The refeeding phase consisted of 84 days and commenced after the animals arrived at the fattening farm. The effect of the transportation system on animals’ weight, metabolic hormones, and serum biochemistry was assessed after 28, 56, and 84 days. During the transportation phase, animals in the droving group lost 10.11 kg and animals in the truck group gained 13.1 kg. The truck group showed 20.5 kg of weight gain at the end of the refeeding phase. The highest triiodothyronine (T₃) and thyroxine (T₄) concentrations were observed on days 0 and 60 in the transportation phase in both droving and truck groups. The serum cortisol concentration was higher in the droving group than in the truck group on day 56 of the refeeding phase. The IGF-I concentrations were higher during the refeeding phase in the droving group than in the truck group. Our results showed that transportation by droving leads to increased weight loss and reduced further weight gain compared to transportation by truck and that serum concentrations of T₄, cortisol, and insulin-like growth factor (IGF-I) hormones are altered by the transportation system.     

Effect of Oil Overlay on Inhibition Potential of Roscovitine in Sheep Cumulus‐Oocyte Complexes

Inhibitors of cyclin‐dependent kinases, as roscovitine, have been used to prevent the spontaneous resumption of meiosis in vitro and to improve the oocyte developmental competence. In this study, the interference of oil overlay on the reversible arrest capacity of roscovitine in sheep oocytes as well as its effects on cumulus expansion was evaluated. For this, cumulus‐oocyte complexes (COCs) were cultured for 20 h in TCM 199 with 10% foetal bovine serum (Control) containing 75 μm roscovitine (Rosco). Subsequently, they were in vitro matured (IVM) for further 18 h in inhibitor‐free medium with LH and FSH. The culture was performed in Petri dishes under mineral oil (+) or in 96 well plates without oil overlay (?) at 38.5°C and 5% CO₂. At 20 and 38 h, the cumulus expansion and nuclear maturation were evaluated under stereomicroscope and by Hoechst 33342 staining, respectively. No group presented cumulus expansion at 20 h. After additional culture with gonadotrophins, a significant rate of COCs from both Control groups (+/?) exhibited total expansion while in both Rosco groups (+/?) the partial expansion prevailed. Among the oocytes treated with roscovitine, 65.2% were kept at GV in the absence of oil overlay while 40.6% of them reached MII under oil cover (p < 0.05). This meiotic arrest was reversible, and proper meiosis progression also occurred in the Control groups (+/?). So, the culture system without oil overlay improved the meiotic inhibition promoted by roscovitine without affecting the cumulus expansion rate or the subsequent meiosis progression.     

Influence of condensed tannin on intake, digestibility, and efficiency of protein utilization in beef steers fed high concentrate diet

This trial was conducted to evaluate if the effect of condensed tannin (CT) is associated with a true protein source on intake, ruminal and total digestibility, ruminal digestion rate, protein efficiency, and microbial efficiency in beef steers fed high concentrate diet (87% of DM). Four Bos indicus steers (407 ± 12 kg of BW) fitted with rumen cannula were assigned to a 4 × 4 Latin square design, arranged in a 2 × 2 factorial arrangement. Treatments consisted of either inclusion (0.4% of DM) or exclusion of condensed tannin (CT) from quebracho extract (76% of CT) with or without the use of soybean meal (SBM) as source of true protein. The level of inclusion was calculated to provide a daily intake of 1 g/10 kg of BW of CT. Intake of DM and nutrients was not affected (P > 0.10) by CT inclusion. However, there was an effect (P < 0.10) of CT inclusion on ether extract digestibility. An interaction (P < 0.10) was observed between CT and SBM on ruminal digestibility and digestion rate of crude protein (CP): when mixed with soybean meal, CT decreased the ruminal digestibility and, consequently, reduced the digestion rate of CP. Intake of CP increased (P < 0.10) with the inclusion of SBM. No differences in DM passage rate were observed (P > 0.10) among treatments. Effects of the interaction (P < 0.10) between CT and SBM were observed on flux of rumen undegradable protein (RUP), metabolizable protein (MP), and on the ratio MP:CP. In the presence of soybean meal, the addition of CT increased (P < 0.10) the flux of RUP and MP, and improved the ratio MP:CP. The yield of microbial protein on the abomasum and the microbial efficiency did not differ among treatments (P > 0.10). There was no difference (P > 0.10) on the pH, VFA, and ruminal ammonia (N-NH₃) with the addition of condensed tannin. The N-NH₃ increased and the ruminal pH decreased with the inclusion of soybean meal (P < 0.10). The utilization of condensed tannin as an additive in beef cattle diets with high level of concentrate and soybean meal as a source of true protein implies positive effects on crude protein utilization, decreasing digestion rate and ruminal digestibility of crude protein and consequently increasing the levels of metabolizable protein, with no changes in the ruminal fermentation parameters.     

Organogenesis and foetal haemodynamics during the normal gestation of healthy black‐rumped agoutis (Dasyprocta prymnolopha,Wagler, 1831) bred in captivity

The objective of this study was to define the patterns of organogenesis and foetal haemodynamics during the normal gestation of healthy agoutis (Dasyprocta prymnolopha) kept in captivity. Thirty pregnant agoutis that ranged in size from small to medium and weighed between 2.5 and 3 kg underwent B‐mode and Doppler ultrasonography for the biometric evaluation of the foetal organs. The foetal aortic blood flow proved to be predominantly systolic, and the measured flow velocity was 78.89 ± 2.95 cm/s, with a maximum pressure gradient of 2.12 ± 0.27 mmHg. The liver was characterized by its large volume, occupying the entire cranial aspect of the abdominal cavity, and it was associated cranially with the diaphragm and caudally with the stomach. The flow velocity in the portal vein was estimated to equal 12.17 ± 2.37 cm/s, with a resistivity index of 0.82 ± 0.05. The gallbladder was centrally located and protruded cranially towards the diaphragm. The spleen was visualized as an elongated structure with tapered cranial and caudal extremities, and the foetal kidneys were visualized bilaterally in the retroperitoneal region, with the right kidney positioned slightly more cranially than the left. The morphological characterization and hemodynamic analysis of the foetal organs of black‐rumped agoutis via B‐mode and Doppler ultrasonography allow determination of the vascular network and of reference values for the blood flow required for perfusing the anatomical elements essential for maintaining the viability of foetuses at different gestational ages.     

Serological response of guinea pigs to oily and aqueous inactivated vaccines containing a Brazilian isolate of the Bovine Viral Diarrhea Virus (BVDV)

Bovine Viral Diarrhea Virus (BVDV) is widespread in cattle in Brazil and research shows its large antigenic variability. Available vaccines are produced with virus strains isolated in other countries and may not be effective. In this study, inactivated vaccines containing the Brazilian BVDV-Ib IBSP11 isolate were developed and tested on 6 groups of 10 guinea pigs (Cavia porcellus). Animals in groups A and C received an aqueous vaccine (aluminum hydroxide); B and D groups received an oily vaccine (Montanide ISA50); Group E positive-control animals were given an imported commercial vaccine with BVDV-Ia Singer; Group F animals were sham vaccinated (negative control). Groups A, B and E received two doses, and Groups C and D, three, every 21 days. Twelve blood samples were taken, at 21-day intervals over 231 days, and evaluated for antibody titer through virus-neutralization (VN), using a homologous strain (IBSP11), and a heterologous strain (BVDV-Ia NADL). Most animals, 42 days following the first dose, seroconverted to both strains and, after the second dose, there was a significant increase of titers in all groups. The oily formulation induced greater response after the third administration. This increase was not observed with the aqueous vaccines, regardless of the virus used in the VN. Antibody decline was more rapid in animals that received aqueous vaccines. The results showed the importance of studying the influence of endemic strains of commercial vaccines, to improve the efficacy of BVD vaccination. Use of the endemic strain in vaccine formulation presented promising results, as well as the use of guinea pigs as a laboratory model.     

Use of ACP‐104 at Different Dilutions for Sperm Cryopreservation of Dourado,Salminus brasiliensis

The dourado, Salminus brasiliensis, is an important fish in South American river basins. The fish‐farming potential and concerns for its conservation in watersheds has stimulated studies with this species. This study compared the effect of different dilutions of two cryoprotectant solutions on the quality of cryopreserved dourado sperm (duration of motility/motility rate) post‐thawing using three different activating solutions. The cryoprotectant solution ACP‐104 was compared with the cryoprotectant solution most commonly used for dourado, which consists of a mixture of dimethyl sulfoxide, glucose, egg yolk, and distilled water. The semen was mixed following dilutions of semen : cryoprotectant solution: 1:3, 1:9, 1:15, 1:21, and 1:27. The cryopreserved samples were activated using distilled water, 0.45% NaCl or 1% NaHCO₃. The results showed differences in thawed semen using the different activating solutions and cryoprotectant solutions. The glucose‐based cryoprotectant not only resulted in sperm motility equal to or better than that produced by ACP‐104, but the quality was not affected by the dilution. However, the sperm quality improved with increasing dilutions for ACP‐104. Under the conditions tested, the standard cryoprotectant solution is recommended for the cryopreservation of dourado semen because it requires a lower solution volume and, therefore, reduced storage space for the same volume of semen.     

Impact of aquaculture on mangrove areas in the northern Pernambuco Coast (Brazil) using remote sensing and geographic information system

The conversion of mangrove areas into shrimp farming ponds has been indicated as the main activity responsible for the reduction in the area of this ecosystem along the northeastern coast of Brazil. The present study was conducted using remote sensing methods and a geographical information system with the aim of quantifying the participation of this activity in the reduction of the mangrove areas along the northern coast of the State of Pernambuco (northeast, Brazil), where shrimp farming has been implanted in last recent years. From 1973 to 2005, there was reduction of about 2.052 ha of mangrove, 197 ha of which were converted into shrimp ponds. Thus, the real contribution of shrimp farming to this reduction was just 9.6% of the total area. Other anthropogenic activities, such as agriculture, urban expansion and tourism, contributed greatly to the reduction in the mangrove areas along the northern coast of the State of Pernambuco.