Search Results (9)

Long-acting injectable (LAI) formulations have revolutionized veterinary pharmaceuticals by improving patient compliance, minimizing dosage frequency, and improving therapeutic efficacy. These formulations utilize advanced drug delivery technologies, including microspheres, liposomes, oil solutions/suspensions, in situ-forming gels, and implants to achieve extended drug release. Biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL) have been approved by the USFDA and are widely employed in the development of various LAIs, offering controlled drug release and minimizing the side effects. Various classes of veterinary medicines, including non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and reproductive hormones, have been successfully formulated as LAIs. Some remarkable LAI products, such as ProHeart^® (moxidectin), Excede^® (ceftiofur), and POSILACTM (recombinant bovine somatotropin), show clinical relevance and commercial success. This review provides comprehensive information on the formulation strategies currently being used and the emerging technologies in LAIs for veterinary purposes. Additionally, challenges in characterization, in vitro testing, in vitro in vivo correlation (IVIVC), and safety concerns regarding biocompatibility are discussed, along with the prospects for next-generation LAIs. Continued advancement in the field of LAI in veterinary medicine is essential for improving animal health. Full article

The recombinant bovine somatotropin (rbST) is a synthetic hormone developed to mimic the effects of the endogenous growth hormone, also known as bovine somatotropin (bST). Although rbST use in dairy cows is authorized in several countries, it is currently banned in Europe. Different methods for screening and confirmatory detection of rbST were developed, mainly based on LC-MS/MS and immune-enzymatic assays. However, some commercial forms of rbST have above the same amino acid sequence of bST, making it difficult to produce a reliable differentiation of recombinant from endogenous forms. Complementary strategies for indirect detection of rbST can therefore be considered as alternative biomarker-based tools. Untargeted transcriptomics was applied to characterize the microRNAs (miRNA) isolated from milk extracellular vesicles (EVs) in rbST-treated animals, aiming the identification of non-coding biomarkers related to its administration. Sequencing analysis of 63 archive samples collected during previous animal trial allowed for the identification of 35 differentially expressed (DE) miRNAs. A validation study performed by qPCR on a further 70 milk samples from a field survey confirmed the significant upregulation of bta-miR-10167-3p in milk EV from rbST-treated cows. The results obtained suggest the potential use of bta-miR-10167-3p as a non-invasive biomarker to be considered in novel screening strategies, needed to tackle rbST misuse in dairy cows. Full article

The study aimed to assess the effect of long-acting bST treatment, in a dose that only increases IGF-I plasma concentrations, on ovarian and fertility markers of estrous synchronized ewes that were fed to keep their bodyweight. Three experiments were designed to evaluate this effect: in Experiment 1, 18 ewes were distributed in groups (bST 0, 30, 50 mg) to measure plasma IGF-I and insulin for 15 days; in Experiment 2, 92 ewes (5 replicates) in two groups (0 and 30 mg bST) were synchronized using a 6-day progesterone protocol during the breeding season to assess the effect of bST on follicular and luteal performances, estrous and ovulation, and fertility after mating. In Experiment 3, 50 ewes (3 replicates) were used to repeat the study before but during anestrus. Results indicate that 50 mg bST increased IGF-I and insulin plasma concentrations, but 30 mg bST only increased IGF-I concentrations; and that only during the breeding season did 30 mg bST increase the number of lambs born and the reproductive success of ovulatory-sized follicles compared to controls. This occurred without it affecting any other reproductive marker. In conclusion, 30 mg bST treatment may improve oocyte competence for fertility during the breeding season. Full article

The use of recombinant bovine somatotropin (rbST) leads to an increase in variable amounts of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on the lipid profile, liver and kidney function, and physical, chemical, and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, compared with 14 animals in a control group. From the first day after rbST, there was a rise in beta-hydroxybutyrate (β-HBO), possibly due to higher dry matter intake or the biotransformation of NEFA into β-HBO. The treatment did not influence blood glucose, non-esterified fatty acids (NEFAs), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea, or creatinine levels. In 71.3% of the buffalo, there was a gradual increase in milk production, with the maximal response occurring in the first week followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days. Only 7.1% of the animals did not respond. On the 3rd, 5th, 7th, and 10th days after treatment, an increase was found in daily milk production between the two groups equal to 1.04, 1.52, 1.42, and 1.06 L, respectively. In relative terms, this means an increase in milk production, respectively, of 15.1%, 21.0%, 19.8%, and 15.1%. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids, or somatic cell count; however, on the third day after rbST administration, there was a decrease in protein. Notably, from the fifth day, the protein values showed no statistical difference. It can be concluded that the use of rbST in buffalo from the 100th day of lactation is metabolically safe since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein. Full article

Dairy farm profitability depends on milk yield, so the dairy industry manages cows to improve their productivity. Both bovine somatotropin (bST) and early lactation increased milking frequency (IMF) and milk yield (MY) in dairy cows. The objective of this study was to evaluate the effects of mid-lactation bST administration on milk production in established lactation when combined with the milk yield carry-over effect from early lactation IMF. Thirteen multiparous Holstein cows were milked unilaterally for 20 days in early lactation. The left udder halves were milked twice daily (2X) and the right udder halves were milked four times daily (4X). Udder halves milked 4X produced 8.60 ± 1.40 kg more than 2X on the final day of IMF treatment. Cows were then returned to 2X milking for the remainder of lactation and sampled on alternate days from 74–94 days in milk (DIM). Bovine somatotropin was administered to all cows at 80 DIM. The 4X halves continued to make 2.66 ± 0.12 kg/d more milk than 2X through 94 DIM. Fat, protein, and lactose yields were significantly greater in the 4X halves compared to the 2X from 74–94 DIM. Overall milk yield increased by 2.71 kg/d with bST administration. However, there was no significant interaction between MF and bST administration. We can infer from these data that the mechanisms by which bST and IMF in early lactation increase milk yield are complementary due to their non-synergistic nature of enhancing MY. Full article

Somatotropin is a species-specific polypeptide hormone produced in the pituitary gland of vertebrates. When administered exogenously to cattle, it can increase milk yield. However, the trade and administration of recombinant bovine somatotropin (rbST) to farm animals have been banned in the European Union (EU). Aside from food safety issues, very little is known about the effects of this hormone on milk composition and quality. In this work, a wide profile of fatty acids (the so-called fatty acidome) was determined by GC-FID in raw milk collected from control and rbST-treated lactating cows in a multidose longitudinal study. Milk composition (lactose, protein, fat, dry matter), including minerals (Ca, K, Mg, Na, P), was also determined, and milk yield was recorded. A tendency toward a less saturated profile was observed in the milk collected from animals treated with rbST, with higher concentrations of monounsaturated fatty acids. In addition, less calcium and potassium and more lactose and protein content were observed in milk from treated animals than in regular milk. As a result of this multicomponent profiling of milk, a clear impact of somatotropin treatment on milk quality was observed. The obtained results should be particularly interesting for those countries that permit the use of this hormone in dairy production. Full article

The use of peptides in immunoassays can be favored over the use of the full protein when more cost effective or less toxic approaches are needed, or when access to the full protein is lacking. Due to restricted access to recombinant bovine somatotropin (rbST), a protein enhancing growth and lactating performances of livestock, which use has been banned in the EU, Canada and Australia (amongst others), we developed a peptide-based biorecognition assay on an imaging planar array analyzer. For this, we identified the rbST epitope that is responsible for binding to the rbST-targeting monoclonal antibody 4H12 (MAb 4H12) to be ₁₁₅DLEEGILALMR₁₂₅. This linear peptide was synthesized and coupled to microspheres, after which it was tested in a biorecognition competitive inhibition assay format. We observed IC₅₀ values of approximately 0.11 μg mL⁻¹, which are lower than observed for the full rbST protein (IC₅₀ = 0.20 μg mL⁻¹). Importantly, there was no binding with the scrambled peptide. Preliminary results of directly coupled peptides in a microsphere biorecognition assay for detection of rbST are presented. Real-life applicability for detection of somatotropins (STs) in injection preparations of bovine-, porcine- and equine ST are shown. This newly developed immunoassay strongly supports future developments of peptide-based immunoassays to circumvent the limited access to the full protein. Full article

Recombinant bovine growth hormone (rbGH) is produced in large quantities and widely used in a number of countries worldwide to stimulate milk production in dairy animals. The use of this compound in animal production is strictly regulated by food safety directives in force, in particular in the European Union (EU). Although analytical strategies for the detection of rbGH in blood have been successfully reported over the past 15 years, they do not fully answer the expectations of either competent authorities or industrials that would expect measuring its occurrence directly in the milk. As a matrix of excretion but also of consumption, milk appears indeed as the matrix of choice for detecting the use of rbGH in dairy animals. It also allows large volumes to be collected without presenting an invasive character for the animal. However, rbGH detection in milk presents several challenges, mainly related to the sensitivity required for its detection in a complex biological matrix. This review article presents the specific difficulties associated with milk and provides an overview of the analytical strategies reported in the literature and whether they concern indirect or direct approaches to the detection of rbGH administration to animals, with applications either for screening or confirmation purposes. Full article

The use of recombinant bovine somatotropin (rbST) in dairy cattle is forbidden in the European Union. Due to the very low circulating concentration of rbST in treated animals, its direct detection is still a challenge. Therefore, the use of indirect methods to detect the ab(use) of rbST in dairy cattle appears as a good alternative. In the past few years, gene expression demonstrated its utility in screening the use of illicit substances in both humans and animals. In this study, a comparison of three types of matrices (milk somatic cells, blood, and hair follicles) was carried out to evaluate their potential use for routine control of rbST using 15 gene-expression profiles. A total of six rbST-treated cows and three control cows were included in the study. A subcutaneous injection containing 500 mg of rbST was administered to the treated group. Samples of the three matrices were collected before rbST administration, and at three and nine days after treatment. The quality of RNA extracted was higher in the blood and hair-follicle samples than in the milk somatic cells. In the three matrices, there were significant differences in the expression of some genes, with milk somatic cells and blood presenting the the best matrices. On this note, the cyclin D1 (CCND1), interleukin 1 beta (IL-1β), tumor necrosis factor (TNF), and insulin-like growth factor 1 receptor (IGF-1R) genes showed potential as biomarkers of rbST treatment. Therefore, blood, somatic cells, and follicle hair should be considered as promising sources of RNA, and can be used in gene-expression assays to routinely control the illicit use of rbST. Full article